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Sample records for second-line salvage treatment

  1. Second line treatment options for pancreatic cancer.

    PubMed

    Passero, Frank C; Saif, Muhammad Wasif

    2017-08-18

    ABTRACT Introduction: Patients with advanced pancreatic cancer (APC) refractory to first-line therapy have a dismal prognosis and limited therapeutic options, with only one option consisting of nanoliposomal irinotecan in combination with fluorouracil and folinic acid which was approved by FDA based upon results of the phase III NAPOLI-1 study. Areas covered: We performed a literature search for relevant published clinical trials, abstracts of trials in progress and ongoing or planned trials for the second line treatment of APC using Pubmed.com, ClinicalTrials.gov and American Society of Clinical Oncology (ASCO) abstract search as sources. We present an in-depth analysis of the phase I-III clinical trials determining the role and efficacy of second-line treatment in patients with APC. We also describe ongoing studies and rationale for future investigation. Expert opinion: Despite advances in first-line therapy such as gemcitabine/nab-paclitaxel and FOLFIRINOX in APC, median overall survival remains less than 12 months, highlighting the need to develop second-line therapies. In order to establish much needed effective second-line treatment options, we need cooperative efforts among institutions and community practices in enrolling these refractory patients in clinical trials. It should be emphasized that in addition to chemotherapy options, all patients should have the opportunity to consult with nutritionist, social worker and palliative care health providers to assist with goals of care, symptom management and end of life discussions.

  2. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort.

    PubMed

    Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

    2015-06-30

    Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.

  3. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort

    PubMed Central

    Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

    2015-01-01

    BACKGROUND Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. PATIENTS AND METHODS Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. RESULTS Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3–7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). CONCLUSION Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies. PMID:25944689

  4. Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a meta-analysis.

    PubMed

    Kim, H S; Kim, H J; Kim, S Y; Kim, T Y; Lee, K W; Baek, S K; Kim, T Y; Ryu, M H; Nam, B H; Zang, D Y

    2013-11-01

    Many patients with refractory or relapsed gastric cancer after first-line chemotherapy have received salvage chemotherapy in routine clinical practice. However, there was no evidence to support this treatment until recent phase III trials demonstrated substantial prolongation of overall survival. Therefore, we conducted a meta-analysis of these trials and investigated whether second-line chemotherapy was more effective than best supportive care. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, 2013), MEDLINE (1950 to March week 4, 2013) and EMBASE (1980-2013, week 13). In addition, we searched all abstracts and virtual meeting presentations from the American Society of Clinical Oncology (ASCO) conferences held between 2004 and 2013. The search process yielded 578 studies, two of which were randomized phase III trials that compared chemotherapy with supportive care. From the abstracts and virtual meeting presentations of ASCO held between 2004 and 2013, 127 abstracts were identified that evaluated second-line chemotherapy; only one relevant abstract was included in the meta-analysis. A total of 410 patients were eligible for analysis, of whom 150 received docetaxel chemotherapy, and 81 received irinotecan chemotherapy. A significant reduction in the risk of death [HR = 0.64, 95% confidence interval (CI) 0.52-0.79, P < 0.0001] was observed with salvage chemotherapy. When the analysis was restricted to irinotecan or docetaxel, there was still significant reduction in the risk of death with each chemotherapeutic agent. The HR was 0.55 (95% CI 0.40-0.77, P = 0.0004) for irinotecan and 0.71 (95% CI 0.56-0.90, P = 0.004) for docetaxel. This meta-analysis demonstrated evidence to support second-line chemotherapy in advanced gastric cancer.

  5. Second-line single-agent versus doublet chemotherapy as salvage therapy for metastatic urothelial cancer: a systematic review and meta-analysis.

    PubMed

    Raggi, D; Miceli, R; Sonpavde, G; Giannatempo, P; Mariani, L; Galsky, M D; Bellmunt, J; Necchi, A

    2016-01-01

    The efficacy and safety of a combination of chemotherapeutic agent compared with single-agent chemotherapy in the second-line setting of advanced urothelial carcinoma (UC) are unclear. We aimed to study the survival impact of single-agent compared with doublet chemotherapy as second-line chemotherapy of advanced UC. Literature was searched for studies including single-agent or doublet chemotherapy in the second-line setting after platinum-based chemotherapy. Random-effects models were used to pool trial-level data according to treatment arm, including median progression-free survival (PFS), overall survival (OS), objective response rate (ORR) probability, and grade 3-4 toxicity. Univariable and multivariable analyses, including sensitivity analyses, were carried out, adjusting for the percent of patients with ECOG performance status ≥1 and hepatic metastases. Forty-six arms of trials including 1910 patients were selected: 22 arms with single agent (n = 1202) and 24 arms with doublets (n = 708). The pooled ORR with single agents was 14.2% [95% confidence interval (CI) 11.1-17.9] versus 31.9% [95% CI 27.3-36.9] with doublet chemotherapy. Pooled median PFS was 2.69 and 4.05 months, respectively. The pooled median OS was 6.98 and 8.50 months, respectively. Multivariably, the odds ratio for ORR and the pooled median difference of PFS were statistically significant (P < 0.001 and P = 0.002) whereas the median difference in OS was not (P = 0.284). When including single-agent vinflunine or taxanes only, differences were significant only for ORR (P < 0.001) favoring doublet chemotherapy. No statistically significant differences in grade 3-4 toxicity were seen between the two groups. Despite significant improvements in ORR and PFS, doublet regimens did not extend OS compared with single agents for the second-line chemotherapy of UC. Prospective trials are necessary to elucidate the role of combination chemotherapy, with or without targeted agents, in the salvage setting

  6. Doublet Versus Single Agent as Second-Line Treatment for Advanced Gastric Cancer

    PubMed Central

    Zhang, Yong; Ma, Bing; Huang, Xiao-Tian; Li, Yan-Song; Wang, Yu; Liu, Zhou-Lu

    2016-01-01

    Abstract The purpose of this study was to perform a meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of doublet versus single agent as second-line treatment for advanced gastric cancer (AGC). A comprehensive literature search was performed to identify relevant RCTs. All clinical studies were independently identified by 2 authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive Meta-Analysis software (Version 2.0). Ten RCTs involving 1698 pretreated AGC patients were ultimately identified. The pooled results demonstrated that doublet combination therapy as second-line treatment for AGC significantly improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI]: 0.78–0.97, P = 0.011), PFS (HR 0.79, 95% CI: 0.72–0.87, P < 0.001), and ORR (relative risk [RR] 1.57, 95% CI: 1.27–1.95, P < 0.001). Sub-group analysis according to treatment regimens also showed that targeted agent plus chemotherapy significantly improve OS, PFS, and ORR. However, no significant survival benefits had been observed in doublet cytotoxic chemotherapy when compared with single cytotoxic agent. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities, diarrhea, and fatigue were observed in doublet combination groups, while equivalent frequencies of grade 3 or 4 thrombocytopenia and nausea were found between the 2 groups. In comparison with single cytotoxic agent alone, the addition of targeted agent to mono-chemotherapy as salvage treatment for pretreated AGC patients provide substantial survival benefits, while no significant survival benefits were observed in doublet cytotoxic chemotherapy regimens. PMID:26937908

  7. Metastatic gastric cancer treatment: Second line and beyond

    PubMed Central

    Ghosn, Marwan; Tabchi, Samer; Kourie, Hampig Raphael; Tehfe, Mustapha

    2016-01-01

    Advanced gastric cancer (aGC), not amenable to curative surgery, is still a burdensome illness tormenting afflicted patients and their healthcare providers. Whereas combination chemotherapy has been shown to improve survival and tumor related symptoms in the frontline setting, second-line therapy (SLT) is subject to much debate in the scientific community, mainly because of the debilitating effects of GC, which would impede the administration of cytotoxic therapy. Recent data has provided sufficient evidence for the safe use of SLT in patients with an adequate performance status. Taxanes, Irinotecan and even some Fluoropyrimidine analogs were found to provide a survival advantage in this subset of patients. Most importantly, quality of life measures were also improved through the use of adequate therapy. Even more pertinent were the findings involving antiangiogenic agents, which would add measurable improvements without significantly jeopardizing the patients’ well-being. Further lines of therapy are cause for much more debate nowadays, but specific targeted agents have shown considerable promise in this context. We herein review noteworthy published data involving the use of additional lines of the therapy after failure of standard frontline therapies in patients with aGC. PMID:27003986

  8. Pharmacogenomics of second-line drugs used for treatment of unresponsive or relapsed osteosarcoma patients.

    PubMed

    Hattinger, Claudia M; Vella, Serena; Tavanti, Elisa; Fanelli, Marilù; Picci, Piero; Serra, Massimo

    2016-12-01

    Second-line treatment of high-grade osteosarcoma (HGOS) patients is based on different approaches and chemotherapy protocols, which are not yet standardized. Although several drugs have been used in HGOS second-line protocols, none of them has provided fully satisfactory results and the role of rescue chemotherapy is not well defined yet. This article focuses on the drugs that have most frequently been used for second-line treatment of HGOS, highlighting the present knowledge on their mechanisms of action and resistance and on gene polymorphisms with possible impact on treatment sensitivity or toxicity. In the near future, validation of the so far identified candidate genetic biomarkers may constitute the basis for tailoring treatment by taking the patients' genetic background into account.

  9. Symptom burden & quality of life among patients receiving second-line treatment of metastatic colorectal cancer

    PubMed Central

    2012-01-01

    Background Bevacizumab (B) and cetuximab (C) are both approved for use in the treatment of metastatic colorectal cancer (mCRC) in the second-line. We examined patient reported symptom burden during second-line treatment of mCRC. Methods Adult mCRC patients treated in the second-line setting with a regimen that included B, C, or chemotherapy only (O) and who had completed ≥ 1 Patient Care Monitor (PCM) surveys as part of routine clinical care were drawn from the ACORN Data Warehouse. Primary endpoints were rash, dry skin, itching, nail changes, nausea, vomiting, fatigue, burning in hands/feet, and diarrhea. Linear mixed models examined change in PCM scores across B, C and O (B = reference). Results 182 patients were enrolled (B: n = 106, C: n = 38, O: n = 38). Patients were 51% female, 67% Caucasian, with mean age of 62.0 (SD = 12.6). Groups did not differ on demographic or clinical characteristics. The most common second-line regimens were FOLFIRI ± B or C (23.1%) and FOLFOX ± B or C (22.5%). Results showed baseline scores to be strongly predictive of second-line symptoms across all PCM items (all p’s < .0001 except for Rash, p = .0013). Controlling for baseline, patients on B tended to have more stable and less severe symptoms. Patients on C had more severe rash, dry skin, and itching and had nail change scores that worsened faster than did B patients. Conclusions Patients receiving second-line treatment for mCRC with B report less symptom burden, especially dermatologic, compared to patients treated with C. PMID:22716038

  10. Standardised second-line treatment of multidrug-resistant tuberculosis during pregnancy.

    PubMed

    Tabarsi, P; Moradi, A; Baghaei, P; Marjani, M; Shamaei, M; Mansouri, N; Chitsaz, E; Farnia, P; Mansouri, D; Masjedi, M; Velayati, A

    2011-04-01

    We describe the efficacy and outcome of standardised second-line anti-tuberculosis (TB) medications during pregnancy. Treatment outcomes of five pregnant women with documented multidrug-resistant TB (MDR-TB) referred to the National Research Institute of Tuberculosis and Lung Diseases from 2003 to 2009 were analysed in two categories, maternal and neonatal. Patients became pregnant during treatment for MDR-TB without any changes in their anti-tuberculosis regimen. None of them had any adverse effects during pregnancy and delivery. No adverse effects were observed in mothers or neonates. The treatment of MDR-TB during pregnancy with a standardised second-line regimen in this study population was safe, with an acceptable rate of treatment success.

  11. Accelerated second-line or maintenance chemotherapy versus treatment at disease progression in NSCLC.

    PubMed

    Velez, Michel; Belalcazar, Astrid; Domingo, Gelenis; Blaya, Marcelo; Raez, Luis E; Santos, Edgardo S

    2010-04-01

    For many decades, the use of chemotherapy as second-line therapy in non-small-cell lung cancer relied upon disease progression. Several studies have shown that four to six cycles of chemotherapy administered as front-line therapy treatment offers a survival advantage to patients; however, further chemotherapy beyond this initial treatment was more associated with side effects and no benefit in survival. Until 2009, second-line treatment for lung cancer was well established for three therapeutic agents: docetaxel, pemetrexed and erlotinib. Currently, the timeframe to use these agents has been challenged by two large randomized clinical trials in which pemetrexed (JMEN trial) and erlotinib (Sequential Tarceva in Unresectable NSCLC [SATURN] trial) were used as 'maintenance' therapy and shown to impact progression-free survival and overall survival. This review focuses on the actual dilemma that medical oncologists face in clinical practice in terms of when and to whom maintenance therapy should be applied or if the 'watch and wait' approach prior to start second-line therapy is still advisable.

  12. Posaconazole salvage treatment for invasive fungal infection.

    PubMed

    Kim, Jong Hun; Williams, Kali

    2014-10-01

    Invasive fungal infection (IFI) is an important cause of morbidity and mortality. Posaconazole is a second generation triazole with a broad spectrum, and it may be suitable for salvage antifungal treatment although posaconazole is not usually considered to be as first-line antifungal therapy for IFI. The purpose of this study was to assess the utility of posaconazole salvage treatment for IFI. We conducted a retrospective review of patients with salvage antifungal treatment with posaconazole for IFI at our institution between December 2007 and July 2012. A total of ten patients received posaconazole salvage IFI. Etiology of IFI was consisting of mucormycosis (four patients), Paecilomyces variotii (one patient), and unspecified IFI etiology (five patients). Causes of posaconazole treatment were following; intolerance of previous antifungal therapy in five patients, refractory IFI on previous antifungal therapy in four patients, and both intolerance of previous antifungal therapy and refractory IFI on previous antifungal therapy in one patient. Duration of posaconazole salvage treatment ranged from 15 to 355 days with median 47 days. The overall successful posaconazole salvage treatment response rate was 80.0 % (8 of 10 patients). There were three patients who died during the study period. However, only one death was attributed to the progression of IFI. Two patients discontinued posaconazole due to adverse events. Posaconazole salvage treatment was effective antifungal therapy for IFI. Further studies are needed to define the optimal therapeutic strategy.

  13. Adherence and persistence among chronic myeloid leukemia patients during second-line tyrosine kinase inhibitor treatment.

    PubMed

    Trivedi, Digisha; Landsman-Blumberg, Pamela; Darkow, Theodore; Smith, David; McMorrow, Donna; Mullins, C Daniel

    2014-10-01

    Chronic myeloid leukemia (CML) treatment is lifelong, and while it is important for patients to remain adherent to treatment, there are conflicting findings with respect to differences in adherence and persistence with dasatinib or nilotinib during second-line treatment.  To compare the rates of adherence, persistence, and discontinuation of 2 oral second-generation tyrosine kinase inhibitors (TKI), dasatinib and nilotinib, in CML patients during their first 12 months of second-line treatment.  Adult CML patients (ICD-9-CM: 205.1x) with 2 consecutive dasatinib or nilotinib prescription claims within 12 months were identified from the Truven Health MarketScan Databases (January 1, 2006-September 30, 2011). Patients were excluded if they had FDA-approved non-CML indications for imatinib, had less than  6 months continuous enrollment, or had a stem cell/bone marrow transplant in the 6 months pre-index. Patients were followed until the first occurrence of index TKI discontinuation/switch; enrollment end; December 31, 2011; or 12 months follow-up post-index. Index treatment (dasatinib ≤ 100 mg or nilotinib) was categorized as second-line if there was evidence of only 1 alternative TKI exposure (e.g., imatinib, dasatinib, or nilotinib) anytime during the patient's available claims history. When comparing adherence, persistence, and discontinuation, inverse probability treatment weighting (IPTW) was used. Adherence and persistence measures were calculated as specified by the International Society for Pharmacoeconomics and Outcomes Research Medication Compliance and Persistence Special Interest Group. Treatment adherence was calculated using medication possession ratio (MPR) and was reported as both continuous and binary measures (i.e., high adherence = MPR ≥ 85%). Persistence was reported as the proportion of days covered (PDC) and estimated level of persistence (ELPT). Finally, discontinuation was defined as a treatment gap of greater than 90 days and

  14. Evaluating antidepressant treatment prior to adding second-line therapies among patients with treatment-resistant depression.

    PubMed

    Hassan, Amany K; Farmer, Kevin C; Brahm, Nancy C; Neas, Barbara R

    2016-04-01

    Patients with depression can be mistakenly labeled as treatment-resistant if they fail to receive an adequate first-line antidepressant trial. Adding second-line agents to the treatment regimens can create an additional burden on both the patients and the healthcare system. To determine if depressed patients receive an adequate antidepressant trial prior to starting second-line therapy and to investigate the association between the type of second-line treatment and severity of illness or depression among unipolar versus bipolar patients. Oklahoma Medicaid claims data between 2006 and 2011. Subjects were depression-diagnosed adult patients with at least two prescriptions of antidepressants followed by a second-line agent. Patients were categorized into one of three groups: an atypical antipsychotic, other augmentation agents (lithium, buspirone, and triiodothyronine), or adding antidepressants, based on the type of second-line therapy. An adequate trial was defined per the American Psychiatric Association guidelines. Factors associated with the type of treatment were tested using multinomial logistic regression models stratified by type of depression (unipolar vs. bipolar patients). Variables used to measure receiving an adequate antidepressant trial included: trial duration, adherence, dose adequacy, and number of distinct antidepressant trials. A total of 3910 patients were included in the analysis. Most subjects reached the recommended antidepressant dose. However, 28 % of patients had an antidepressant trial duration <4 weeks and only 60 % tried at least two antidepressant regimens prior to adding second-line therapy. Approximately 50 % of the subjects were non-adherent across all groups. Severity of illness and receipt of an adequate antidepressant trial were not predictors of the type of second-line treatment. Many patients do not receive an adequate antidepressant trial before starting a second-line agent. The type of second-line treatment was independent of

  15. Economic evaluation of eribulin as second-line treatment for metastatic breast cancer in South Korea

    PubMed Central

    Tremblay, Gabriel; Majethia, Unnati; Breeze, Janis L; Kontoudis, Ilias; Park, Jeongae

    2016-01-01

    Background Metastatic breast cancer (MBC) is associated with poor prognosis, particularly for those patients with human epidermal growth factor receptor (HER2)-negative tumor. Similar to the rest of the world, treatment options are limited in South Korea following first-line chemotherapy with anthracyclines and/or taxanes. This study examined the cost-effectiveness and cost-utility of eribulin in South Korean patients with HER2-negative MBC who have progressed after usage of at least one chemotherapeutic regimen for advanced disease (second-line therapy). Methods A partition survival model was developed from the perspective of the South Korean health care system. The economic impact of introducing eribulin as second-line therapy for HER2-negative MBC was compared to that of capecitabine and vinorelbine. The analysis estimated incremental cost per life-year (LY), that is, cost-effectiveness, and cost per quality-adjusted life-year (QALY), that is, cost-utility, of eribulin for management of HER2-negative MBC in South Korea. The model accounted for overall survival, progression-free survival, drug costs, grade 3/4 adverse events, and health care utilization. Deterministic and probabilistic sensitivity analyses were performed to identify uncertainty in the results of the economic evaluation. Results Second-line eribulin was associated with greater benefits in terms of LY and QALY, compared to capecitabine and vinorelbine. The incremental cost-effectiveness ratio was ₩10.5M (approximately USD 9,200) per LY, and the incremental cost-utility ratio was ₩17M (approximately USD 14,800) per QALY in the basecase analysis. The incremental cost-utility ratio ranged from ₩12M (USD 10,461) to ₩27M (USD 23,538) per QALY in the deterministic sensitivity analysis. In the probabilistic sensitivity analysis, >99% of the simulations were below ₩50M (USD 42,300), and the lower and upper 95% confidence intervals were ₩3M (USD 2,600) and ₩24M (USD 20,900) per QALY

  16. Economic evaluation of eribulin as second-line treatment for metastatic breast cancer in South Korea.

    PubMed

    Tremblay, Gabriel; Majethia, Unnati; Breeze, Janis L; Kontoudis, Ilias; Park, Jeongae

    2016-01-01

    Metastatic breast cancer (MBC) is associated with poor prognosis, particularly for those patients with human epidermal growth factor receptor (HER2)-negative tumor. Similar to the rest of the world, treatment options are limited in South Korea following first-line chemotherapy with anthracyclines and/or taxanes. This study examined the cost-effectiveness and cost-utility of eribulin in South Korean patients with HER2-negative MBC who have progressed after usage of at least one chemotherapeutic regimen for advanced disease (second-line therapy). A partition survival model was developed from the perspective of the South Korean health care system. The economic impact of introducing eribulin as second-line therapy for HER2-negative MBC was compared to that of capecitabine and vinorelbine. The analysis estimated incremental cost per life-year (LY), that is, cost-effectiveness, and cost per quality-adjusted life-year (QALY), that is, cost-utility, of eribulin for management of HER2-negative MBC in South Korea. The model accounted for overall survival, progression-free survival, drug costs, grade 3/4 adverse events, and health care utilization. Deterministic and probabilistic sensitivity analyses were performed to identify uncertainty in the results of the economic evaluation. Second-line eribulin was associated with greater benefits in terms of LY and QALY, compared to capecitabine and vinorelbine. The incremental cost-effectiveness ratio was ₩10.5M (approximately USD 9,200) per LY, and the incremental cost-utility ratio was ₩17M (approximately USD 14,800) per QALY in the basecase analysis. The incremental cost-utility ratio ranged from ₩12M (USD 10,461) to ₩27M (USD 23,538) per QALY in the deterministic sensitivity analysis. In the probabilistic sensitivity analysis, >99% of the simulations were below ₩50M (USD 42,300), and the lower and upper 95% confidence intervals were ₩3M (USD 2,600) and ₩24M (USD 20,900) per QALY, respectively. There currently exist

  17. Second line drug susceptibility testing to inform the treatment of rifampin-resistant tuberculosis: a quantitative perspective.

    PubMed

    Kendall, Emily A; Cohen, Ted; Mitnick, Carole D; Dowdy, David W

    2017-03-01

    Treatment failure and resistance amplification are common among patients with rifampin-resistant tuberculosis (TB). Drug susceptibility testing (DST) for second-line drugs is recommended for these patients, but logistical difficulties have impeded widespread implementation of second-line DST in many settings. To provide a quantitative perspective on the decision to scale up second-line DST, we synthesize literature on the prevalence of second-line drug resistance, the expected clinical and epidemiologic benefits of using second-line DST to ensure that patients with rifampin-resistant TB receive effective regimens, and the costs of implementing (or not implementing) second-line DST for all individuals diagnosed with rifampin-resistant TB. We conclude that, in most settings, second-line DST could substantially improve treatment outcomes for patients with rifampin-resistant TB, reduce transmission of drug-resistant TB, prevent amplification of drug resistance, and be affordable or even cost-saving. Given the large investment made in each patient treated for rifampin-resistant TB, these payoffs would come at relatively small incremental cost. These anticipated benefits likely justify addressing the real challenges faced in implementing second-line DST in most high-burden settings.

  18. A biregional survey and review of first-line treatment failure and second-line paediatric antiretroviral access and use in Asia and southern Africa

    PubMed Central

    2011-01-01

    Background To better understand the need for paediatric second-line antiretroviral therapy (ART), an ART management survey and a cross-sectional analysis of second-line ART use were conducted in the TREAT Asia Paediatric HIV Observational Database and the IeDEA Southern Africa (International Epidemiologic Databases to Evaluate AIDS) regional cohorts. Methods Surveys were conducted in April 2009. Analysis data from the Asia cohort were collected in March 2009 from 12 centres in Cambodia, India, Indonesia, Malaysia, and Thailand. Data from the IeDEA Southern Africa cohort were finalized in February 2008 from 10 centres in Malawi, Mozambique, South Africa and Zimbabwe. Results Survey responses reflected inter-regional variations in drug access and national guidelines. A total of 1301 children in the TREAT Asia and 4561 children in the IeDEA Southern Africa cohorts met inclusion criteria for the cross-sectional analysis. Ten percent of Asian and 3.3% of African children were on second-line ART at the time of data transfer. Median age (interquartile range) in months at second-line initiation was 120 (78-145) months in the Asian cohort and 66 (29-112) months in the southern African cohort. Regimens varied, and the then current World Health Organization-recommended nucleoside reverse transcriptase combination of abacavir and didanosine was used in less than 5% of children in each region. Conclusions In order to provide life-long ART for children, better use of current first-line regimens and broader access to heat-stable, paediatric second-line and salvage formulations are needed. There will be limited benefit to earlier diagnosis of treatment failure unless providers and patients have access to appropriate drugs for children to switch to. PMID:21306608

  19. Second-line treatment with carboplatin for recurrent or progressive oligodendroglial tumors after PCV (procarbazine, lomustine, and vincristine) chemotherapy: a phase II study.

    PubMed

    Soffietti, Riccardo; Nobile, Mauro; Rudà, Roberta; Borgognone, Marzia; Costanza, Alessandra; Laguzzi, Elena; Mutani, Roberto

    2004-02-15

    The efficacy of second-line chemotherapy for patients with recurrent or progressive oligodendroglial tumors is limited. In the current study, the authors investigated the use of carboplatin as a second-line chemotherapeutic agent against these types of tumors. Twenty-three patients with recurrent or progressive oligodendrogliomas or oligoastrocytomas after first-line PCV (procarbazine, lomustine, and vincristine) chemotherapy were enrolled in a single-institution Phase II study of second-line carboplatin chemotherapy. All patients had undergone surgery, and most also had undergone conventional radiotherapy. Carboplatin was administered at a dose of 560 mg/m2 intravenously every 4 weeks. Responses were evaluated according to conventional criteria, based on magnetic resonance imaging (MRI) findings. Three of 23 patients (13%) had partial responses, with neurologic improvement. Twelve patients (52%) had stable disease; in 2 of these 12 patients, a minor response was seen on MRI. Eight patients (35%) had progressive disease. The median time to tumor progression was 3 months for all patients and 9 months for patients who experienced responses to treatment. Progression-free survival rates at 6 and 12 months were 34.8% and 8.7%, respectively. Among the salvage treatment plans followed after carboplatin chemotherapy were supportive care alone, radiotherapy, third-line chemotherapy, and reoperation. The median survival duration from the start of carboplatin administration was 16 months. Myelotoxicity was severe, with Grade 3 or 4 thrombocytopenia in 60% of patients and Grade 3 or 4 neutropenia in 48% of patients. When administered according to a monthly schedule, carboplatin exhibited modest activity in adult patients with recurrent or progressive oligodendroglioma or oligoastrocytoma who experienced treatment failure after PCV chemotherapy; the current treatment regimen also was associated with severe toxicity. Further improvement of second-line chemotherapy for the

  20. Second-Line Treatment of NSCLC-The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms.

    PubMed

    Köhler, Jens

    2017-01-01

    In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif(®)) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of the EGFR mutational status (LUX-Lung 8). Contrariwise, results from the TAILOR and DELTA trials among retrospective biomarker analyses show the predictive value of the EGFR mutational status for efficacy of reversible EGFR inhibitors also as a second-line therapy. This mini review critically summarizes the current role of EGFR-targeting strategies in the second-line treatment of NSCLC with special respect to afatinib in light of emerging T790M-specific EGFR and immune check point inhibitors. The review also emphasizes the urgent need for reliable biomarkers to guide therapeutic decision-making and outlines prospective changes to the second-line landscape with some of the current second-line treatment concepts likely to be moved to the first-line.

  1. Second-Line Treatment of NSCLC—The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms

    PubMed Central

    Köhler, Jens

    2017-01-01

    In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activating EGFR mutations, the role of EGFR blockade and of EGFR molecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif®) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of the EGFR mutational status (LUX-Lung 8). Contrariwise, results from the TAILOR and DELTA trials among retrospective biomarker analyses show the predictive value of the EGFR mutational status for efficacy of reversible EGFR inhibitors also as a second-line therapy. This mini review critically summarizes the current role of EGFR-targeting strategies in the second-line treatment of NSCLC with special respect to afatinib in light of emerging T790M-specific EGFR and immune check point inhibitors. The review also emphasizes the urgent need for reliable biomarkers to guide therapeutic decision-making and outlines prospective changes to the second-line landscape with some of the current second-line treatment concepts likely to be moved to the first-line. PMID:28243590

  2. Hypothyroidism during second-line treatment of multidrug-resistant tuberculosis: a prospective study.

    PubMed

    Bares, R; Khalid, N; Daniel, H; Dittmann, H; Reimold, M; Gallwitz, B; Schmotzer, C

    2016-07-01

    Hypothyroidism is an adverse effect of certain anti-tuberculosis drugs. This is a prospective study of the frequency and possible pathomechanisms associated with hypothyroidism due to second-line treatment of multidrug-resistant tuberculosis. Fifty human immunodeficiency virus negative patients and 20 controls were included. All participants underwent ultrasonography of the thyroid and measurement of thyroid stimulating hormone (TSH). TSH levels were checked every 3 months. If hypothyroidism was present, T3, T4 and thyroid peroxidase autoantibodies were measured, and imaging extended to scintigraphy and repeated ultrasonography. Before treatment, 7 patients (14%) and 1 control (5%) were hypothyreotic. During the first 6 months of treatment, TSH levels increased in 41 patients (82%), 39 (78%) had values above the normal range and 19 (38%) had overt hypothyroidism. As none of the patients had signs of autoimmune thyroiditis, interaction with anti-tuberculosis drugs was assumed to be the cause of hypothyroidism. Nine patients died during treatment, all of whom had developed hypothyroidism. In seven, the metabolic situation at their death was known, and they had become euthyreotic following levothyroxine substitution. TSH levels should be checked before initiating anti-tuberculosis treatment and after 3 and 6 months to start timely replacement of levothyroxine. Further studies are needed to elucidate the exact pathomechanism involved in hypothyroidism and whether hypothyroidism can be used as predictor of treatment failure.

  3. Treatment decisions in metastatic colorectal cancer - Beyond first and second line combination therapies.

    PubMed

    Vogel, A; Hofheinz, R D; Kubicka, S; Arnold, D

    2017-09-01

    Median overall survival (OS) of patients with metastatic colorectal cancer (mCRC) has reached up to 30months in recent clinical trials of first line therapies. Following disease progression after the standard in both, 1st and 2nd line, combination chemotherapy with monoclonal antibodies, many patients maintain a good performance status and a significant proportion is motivated to undergo further therapy. Choices of treatment beyond the second line setting for mCRC are therefore becoming increasingly important. New options have entered the therapeutic field recently: Regorafenib is a multikinase inhibitor approved for mCRC patients who have progressed on chemotherapy (including fluoropyrimidines, irinotecan, and oxaliplatin), plus VEGF inhibitor(s) and - if RAS wild-type - an anti-EGFR inhibitor. Regorafenib significantly improved OS, compared to placebo, in two phase III trials (CORRECT and CONCUR) in mCRC patients. Trifluridine/Tipiracil, an oral fluoropyrimidine, also resulted in significantly improved OS when compared to placebo in the phase III RECOURSE trial, which was conducted in a similar patient population to CORRECT. Reintroduction of previously administered therapy is another valid and commonly used approach, especially for those regimens which were discontinued before progression, e.g. if associated with cumulative toxicities, such as peripheral neuropathy or due to treatment breaks. Re-challenge of drugs to which patients developed resistance is also feasible although evidence for this strategy is limited. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Establishment of a first-line second-line treatment model for human pulmonary adenocarcinoma

    PubMed Central

    Wang, Lining; Wang, Yu; Guan, Qi; Liu, Yong; He, Tianyi; Wang, Jiaru

    2016-01-01

    Lung cancer is one of the most prevalent types of cancer in the world. Surgery, chemotherapy and radiotherapy are used clinically as treatments for numerous cancers. Due to the appearance of drug resistance, the remission rate is limited to 40–50%. Docetaxel and pemetrexed are two drugs commonly used, and their effects in single-phase cell culture are well known. From the pharmacological point of view, it appears rational to hypothesize that sequential therapy effects can show better outcomes compared with traditional single-phase experiments. Considering this, the present study aimed to establish a first-line second-line adenocarcinoma treatment model, using the combination of cisplatin with docetaxel or pemetrexed in vitro in different sequential therapy timings. To test this, the human lung cancer A549 cell line was used. The inhibitory effect was determined by adding docetaxel following treatment with cisplatin and pemetrexed (Pem-Doc group) and comparing this with a group in which pemetrexed was added subsequent to treatment with cisplatin and docetaxel (Doc-Pem group). Additionally, the differences in the gene and protein expression levels of excision repair cross-completion gene 1 (ERCC1), a gene that promotes drug resistance to cisplatin, were compared between the two groups. The present results showed that the inhibitory effect of cell proliferation in the Pem-Doc group was increased compared with that of Doc-Pem group, while the gene expression and protein levels of ERCC1 in the Pem-Doc group were decreased compared with those of Doc-Pem group. The Pem-Doc treatment plan is more effective in inhibiting cell proliferation and in lowering the expression of the ERCC1 gene. Therefore, Pem-Doc may be a more effective adenocarcinoma treatment. PMID:28105156

  5. Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor-Based Antiretroviral Therapy.

    PubMed

    Suaysod, Rapeepan; Ngo-Giang-Huong, Nicole; Salvadori, Nicolas; Cressey, Tim R; Kanjanavanit, Suparat; Techakunakorn, Pornchai; Krikajornkitti, Sawitree; Srirojana, Sakulrat; Laomanit, Laddawan; Chalermpantmetagul, Suwalai; Lallemant, Marc; Le Cœur, Sophie; McIntosh, Kenneth; Traisathit, Patrinee; Jourdain, Gonzague

    2015-07-01

    Human immunodeficiency virus (HIV)-infected children failing second-line antiretroviral therapy (ART) have no access to third-line antiretroviral drugs in many resource-limited settings. It is important to identify risk factors for second-line regimen failure. HIV-infected children initiating protease inhibitor (PI)-containing second-line ART within the Program for HIV Prevention and Treatment observational cohort study in Thailand between 2002 and 2010 were included. Treatment failure was defined as confirmed HIV type 1 RNA load >400 copies/mL after at least 6 months on second-line regimen or death. Adherence was assessed by drug plasma levels and patient self-report. Cox proportional hazards regression analyses were used to identify risk factors for failure. A total of 111 children started a PI-based second-line regimen, including 59 girls (53%). Median first-line ART duration was 1.9 years (interquartile range [IQR], 1.4-3.3 years), and median age at second-line initiation was 10.7 years (IQR, 6.3-13.4 years). Fifty-four children (49%) experienced virologic failure, and 2 (2%) died. The risk of treatment failure 24 months after second-line initiation was 41%. In multivariate analyses, failure was independently associated with exposure to first-line ART for >2 years (adjusted hazard ratio [aHR], 1.8; P = .03), age >13 years (aHR, 2.9; P < .001), body mass index-for-age z score < -2 standard deviations at second-line initiation (aHR, 2.8; P = .03), and undetectable drug levels within 6 months following second-line initiation (aHR, 4.5; P < .001). Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Cost-effectiveness of sorafenib for second-line treatment of advanced renal cell carcinoma.

    PubMed

    Hoyle, Martin; Green, Colin; Thompson-Coon, Jo; Liu, Zulian; Welch, Karen; Moxham, Tiffany; Stein, Ken

    2010-01-01

    To estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service. A decision analytic model was developed to estimate the cost-effectiveness of sorafenib. The clinical effectiveness of sorafenib versus BSC was taken from a recent randomized phase III trial. Utility values were taken from a phase II trial of sunitinib, using EQ-5D tariffs. Cost data were obtained from published literature and were based on current UK practice. The effect of parameter uncertainty on cost-effectiveness was explored through extensive one-way and probabilistic sensitivity analyses. Compared to BSC, sorafenib treatment resulted in an incremental cost per quality-adjusted life year (QALY) gained of pound75,398, based on an estimated mean gain of 0.27 QALYs per patient, at a mean additional cost of pound20,063 (inflated to 2007/2008). The probability that sorafenib is cost-effective compared to BSC at a willingness to pay threshold of pound30,000 per QALY is 0.0%. In sensitivity analysis, estimates of cost per QALY were sensitive to changes in the clinical effectiveness parameters, and to health state utilities and drug costs. Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of pound70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.

  7. Drug resistance testing through remote genotyping and predicted treatment options in human immunodeficiency virus type 1 infected Tanzanian subjects failing first or second line antiretroviral therapy.

    PubMed

    Svärd, Jenny; Mugusi, Sabina; Mloka, Doreen; Neogi, Ujjwal; Meini, Genny; Mugusi, Ferdinand; Incardona, Francesca; Zazzi, Maurizio; Sönnerborg, Anders

    2017-01-01

    second line failure) was observed. First line failure subjects displayed a high degree of cross-resistance to second-generation NNRTIs etravirine (ETR; 51% intermediate and 9% resistant) and rilpivirine (RPV; 12% intermediate and 58% resistant), and to abacavir (ABC; 49% resistant) which is reserved for second line therapy in Tanzania. The predicted probability of success with the best salvage regimen at second-line failure decreased from 93.9% to 78.7% when restricting access to the NRTIs, NNRTIs and PIs currently available in Tanzania compared to when including all approved drugs. The split genotyping procedure is potential tool to analyse drug resistance in Tanzania but the sensitivity should be evaluated further. The lack of viral load monitoring likely results in a high false positive rate of treatment failures, unnecessary therapy switches and massive accumulation of NRTI and NNRTI mutations. The introduction of regular virological monitoring should be prioritized and integrated with drug resistance studies in resource limited settings.

  8. Eradication rates of helicobacter pylori infection with second-line treatment: non-ulcer dyspepsia compared to peptic ulcer disease.

    PubMed

    Chung, Su Jin; Lee, Dong Ho; Kim, Nayoung; Jung, Sook Hyang; Kim, Jin Wook; Hwang, Jin Hyeok; Park, Young Soo; Lee, Kwang Hyuk; Jung, Hyun Chae; Song, In Sung

    2007-06-01

    Initial proton pump inhibitor (PPI)-based triple therapy for Helicobacter pylori (H. pylori) infection is less effective in patients with nonulcer dyspepsia (NUD) than those with peptic ulcer disease (PUD). To date, there have been no studies on the difference in eradication rates in NUD compared to PUD with regard to second-line therapy. Therefore, we retrospectively analyzed the difference in eradication rates of a second-line quadruple therapy for NUD and PUD patients. Between June 2003 and December 2005, patients who failed to respond to initial PPI-based triple therapy, received 7 days of quadruple therapy (PPI b.i.d., bismuth 300mg q.i.d., metronidazole 500mg t.i.d., tetracycline 500mg q.i.d.) as a second-line treatment regimen. Four weeks after the completion of the course of medication, a 13C-urea breath test was performed for detection of H. pylori. A total of 87 patients received second-line quadruple therapy. Of these, 43 patients had NUD and 44 patients had PUD (19 gastric ulcers, 23 duodenal ulcers, 2 both ulcers). The eradication rates were 76.7% (33/43) in the NUD group and 90.9% (40/44) in the PUD group by per-protocol analysis. Therefore, the eradication rates in the NUD group were significantly lower than those in the PUD group (p = 0.034). A 7-day bismuth-based second-line quadruple therapy for H. pylori infection was less effective in patients with NUD than those with PUD. Therefore, a more potent second-line treatment regimen or extension of treatment duration of quadruple therapy should be considered for the eradication of H. pylori in patients with NUD.

  9. Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

    PubMed

    Cegielski, J Peter; Kurbatova, Ekaterina; van der Walt, Martie; Brand, Jeannette; Ershova, Julia; Tupasi, Thelma; Caoili, Janice Campos; Dalton, Tracy; Contreras, Carmen; Yagui, Martin; Bayona, Jaime; Kvasnovsky, Charlotte; Leimane, Vaira; Kuksa, Liga; Chen, Michael P; Via, Laura E; Hwang, Soo Hee; Wolfgang, Melanie; Volchenkov, Grigory V; Somova, Tatiana; Smith, Sarah E; Akksilp, Somsak; Wattanaamornkiet, Wanpen; Kim, Hee Jin; Kim, Chang-Ki; Kazennyy, Boris Y; Khorosheva, Tatiana; Kliiman, Kai; Viiklepp, Piret; Jou, Ruwen; Huang, Angela Song-En; Vasilyeva, Irina A; Demikhova, Olga V; Lancaster, Joey; Odendaal, Ronel; Diem, Lois; Perez, Therese C; Gler, Tarcela; Tan, Kathrine; Bonilla, Cesar; Jave, Oswaldo; Asencios, Luis; Yale, Gloria; Suarez, Carmen; Walker, Allison Taylor; Norvaisha, Inga; Skenders, Girts; Sture, Ingrida; Riekstina, Vija; Cirule, Andra; Sigman, Erika; Cho, Sang-Nae; Cai, Ying; Eum, Seokyong; Lee, Jongseok; Park, Seungkyu; Jeon, Doosoo; Shamputa, Isdore C; Metchock, Beverly; Kuznetsova, Tatiana; Akksilp, Rattanawadee; Sitti, Wanlaya; Inyapong, Jirapan; Kiryanova, Elena V; Degtyareva, Irina; Nemtsova, Evgenia S; Levina, Klavdia; Danilovits, Manfred; Kummik, Tiina; Lei, Yung-Chao; Huang, Wei-Lun; Erokhin, Vladislav V; Chernousova, Larisa N; Andreevskaya, Sofia N; Larionova, Elena E; Smirnova, Tatyana G

    2016-02-15

    Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. Patients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens. Of 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome. Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired

  10. Effect of resumption of second line drugs in patients with rheumatoid arthritis that flared up after treatment discontinuation

    PubMed Central

    ten, W; Hermans, J.; Breedveld, F.; Dijkmans, B.

    1997-01-01

    OBJECTIVE—To assess the effect of resumption of second line drugs in patients with rheumatoid arthritis (RA) that flared after treatment discontinuation.
METHODS—RA patients were studied whose RA flared up after discontinuation of second line treatment while being in remission and who received a second course of the drug. Disease activity parameters were prospectively assessed at the time of treatment discontinuation, during the period when the disease flared up, and three months thereafter. Furthermore the medical charts were reviewed at 12 months after treatment resumption.
RESULTS—There were 51 patients included in the study: 25 patients treated with antimalarial drugs, 10 with parenteral gold, four with d-penicillamine, eight with sulphasalazine, two with azathioprine, and two with methotrexate. Disease activity parameters showed significant improvement within three months of treatment resumption, but remained significantly worse when compared with that measured before treatment discontinuation. Within three months 47% of the patients fulfilled 20% response criteria. Disease activity 12 months after treatment resumption was considered to be absent in 35%, mild in 43%, and moderate or active in 22% of the patients. In four (8%) patients the resumed treatment was stopped because of lack of efficacy. Side effects were recorded in four patients, which did not result in treatment discontinuation.
CONCLUSIONS—Resumption of second line drugs in RA patients whose disease flared up after discontinuation of treatment is effective and safe in most patients. Half of the patients responded within three months after resumption of the second line drug.

 PMID:9165995

  11. Imatinib dose escalation versus sunitinib as a second line treatment in KIT exon 11 mutated GIST: a retrospective analysis.

    PubMed

    Vincenzi, Bruno; Nannini, Margherita; Fumagalli, Elena; Bronte, Giuseppe; Frezza, Anna Maria; De Lisi, Delia; Spalato Ceruso, Mariella; Santini, Daniele; Badalamenti, Giuseppe; Pantaleo, Maria Abbondanza; Russo, Antonio; Dei Tos, Angelo Paolo; Casali, Paolo; Tonini, Giuseppe

    2016-10-25

    We retrospectively reviewed data from 123 patients (KIT exon 11 mutated) who received sunitinib or dose-escalated imatinib as second line.All patients progressed on imatinib (400 mg/die) and received a second line treatment with imatinib (800 mg/die) or sunitinib (50 mg/die 4 weeks on/2 off or 37.5 mg/day). Deletion versus other KIT 11 mutation was recorded, correlated with clinical benefits.64% received imatinib, 36% sunitinib. KIT exon 11 mutation was available in 94 patients. With a median follow-up of 61 months, median time to progression (TTP) in patients receiving sunitinib and imatinib was 10 (95% CI 9.7-10.9) and 5 months (95% CI 3.6-6.7) respectively (P = 0.012). No difference was found in overall survival (OS) (P = 0.883). In imatinib arm, KIT exon 11 deletions was associated with a shorter TTP (7 vs 17 months; P = 0.02), with a trend in OS (54 vs 71 months P = 0.063). No difference was found in patients treated with sunitinib (P = 0.370).A second line with sunitinib was associated with an improved TTP in KIT exon 11 mutated patients progressing on imatinib 400 mg/die. Deletions in exon 11 seemed to be correlated with worse outcome in patients receiving imatinib-based second line.

  12. Intratympanic methylprednisolone perfusion as a salvage treatment for profound idiopathic sudden sensorineural hearing loss.

    PubMed

    Dai, Y; Lu, L; Hou, J; Yang, X; Li, H; Yang, Y; She, W

    2017-05-01

    This study aimed to examine the effectiveness of intratympanic methylprednisolone perfusion as salvage treatment for profound idiopathic sudden sensorineural hearing loss. A retrospective clinical study of 97 patients with unilateral profound idiopathic sudden sensorineural hearing loss was performed. In all, 83 patients who received salvage intratympanic methylprednisolone perfusion plus conventional treatment (except for steroids) as the second-line therapy were assigned to the study group, while 14 patients who received conventional treatment alone were assigned to the comparison group. In the study group, treatments in patients with a shorter interval from disease onset to intratympanic methylprednisolone perfusion (up to 15 days) had significantly greater improvements in the overall effective rate and pure tone average compared with patients with a longer interval (over 15 days). For patients with a short interval from disease onset to intratympanic methylprednisolone perfusion, those in the study group had significantly greater improvements in the overall effective rate and pure tone average compared with those in the comparison group. In both the study and comparison groups, hearing improvements were greater at low frequencies than at medium and high frequencies. The interval from disease onset to intratympanic methylprednisolone perfusion was the major factor affecting hearing recovery. Early second-line salvage intratympanic methylprednisolone perfusion significantly improved the degree of hearing recovery in profound idiopathic sudden sensorineural hearing loss patients after failure of systemic steroid treatment.

  13. Second-Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological, and Molecular Aspects of Nintedanib

    PubMed Central

    Corrales, Luis; Nogueira, Amanda; Passiglia, Francesco; Listi, Angela; Caglevic, Christian; Giallombardo, Marco; Raez, Luis; Santos, Edgardo; Rolfo, Christian

    2017-01-01

    Lung carcinoma is the leading cause of death by cancer in the world. Nowadays, most patients will experience disease progression during or after first-line chemotherapy demonstrating the need for new, effective second-line treatments. The only approved second-line therapies for patients without targetable oncogenic drivers are docetaxel, gemcitabine, pemetrexed, and erlotinib and for patients with target-specific oncogenes afatinib, osimertinib, crizotinib, alectinib, and ceritinib. In recent years, evidence on the role of antiangiogenic agents have been established as important and effective therapeutic targets in non-small cell lung cancer (NSCLC). Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors (vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor). Several preclinical and clinical studies have proven the usefulness of nintedanib as an anticancer agent for NSCLC. The most important study was the phase III LUME-Lung 1 trial, which investigated the combination of nintedanib with docetaxel for second-line treatment in advanced NSCLC patients. The significant improvement in overall survival and the manageable safety profile led to the approval of this new treatment in Europe. This review focuses on the preclinical and clinical studies with nintedanib in NSCLC. PMID:28293555

  14. Long-term outcomes of second-line antiretroviral treatment in an adult and adolescent cohort in Myanmar.

    PubMed

    Kyaw, Nang Thu Thu; Kumar, Ajay M V; Oo, Myo Minn; Oo, Htun Nyunt; Kyaw, Khine Wut Yee; Thiha, Soe; Aung, Thet Ko; Win, Than; Mon, Yin Yin; Harries, Anthony D

    2017-01-01

    Myanmar has a high burden of Human Immunodeficiency Virus (HIV) and second-line antiretroviral treatment (ART) has been available since 2008 in the public health sector. However, there have been no published data about the outcomes of such patients until now. To assess the treatment and programmatic outcomes and factors associated with unfavorable outcomes (treatment failure, death and loss to follow-up from care) among people living with HIV (aged ≥ 10 years) receiving protease inhibitor-based second-line ART under the Integrated HIV Care Program in Myanmar between October 2008 and June 2015. Retrospective cohort study using routinely collected program data. Of 824 adults and adolescents on second-line ART, 52 patients received viral load testing and 19 patients were diagnosed with virological failure. However, their treatment was not modified. At the end of a total follow-up duration of 7 years, 88 (11%) patients died, 35 (4%) were lost to follow-up, 21 (2%) were transferred out to other health facilities and 680 (83%) were still under care. The incidence rate of unfavorable outcomes was 7.9 patients per 100 person years follow-up. Patients with a history of injecting drug use, with a history of lost to follow-up, with a higher baseline viral load and who had received didanosine and abacavir had a higher risk of unfavorable outcomes. Patients with higher baseline C4 counts, those having taken first-line ART at a private clinic, receiving ART at decentralized sites and taking zidovudine and lamivudine had a lower risk of unfavorable outcomes. Long-term outcomes of patients on second-line ART were relatively good in this cohort. Virological failure was relatively low, possibly because of lack of viral load testing. No patient who failed on second-line ART was switched to third-line treatment. The National HIV/AIDS Program should consider making routine viral load monitoring and third-line ART drugs available after a careful cost-benefit analysis.

  15. Long-term outcomes of second-line antiretroviral treatment in an adult and adolescent cohort in Myanmar

    PubMed Central

    Kyaw, Nang Thu Thu; Kumar, Ajay M. V.; Oo, Myo Minn; Oo, Htun Nyunt; Kyaw, Khine Wut Yee; Thiha, Soe; Aung, Thet Ko; Win, Than; Mon, Yin Yin; Harries, Anthony D.

    2017-01-01

    ABSTRACT Background: Myanmar has a high burden of Human Immunodeficiency Virus (HIV) and second-line antiretroviral treatment (ART) has been available since 2008 in the public health sector. However, there have been no published data about the outcomes of such patients until now. Objective: To assess the treatment and programmatic outcomes and factors associated with unfavorable outcomes (treatment failure, death and loss to follow-up from care) among people living with HIV (aged ≥ 10 years) receiving protease inhibitor-based second-line ART under the Integrated HIV Care Program in Myanmar between October 2008 and June 2015. Design: Retrospective cohort study using routinely collected program data. Results: Of 824 adults and adolescents on second-line ART, 52 patients received viral load testing and 19 patients were diagnosed with virological failure. However, their treatment was not modified. At the end of a total follow-up duration of 7 years, 88 (11%) patients died, 35 (4%) were lost to follow-up, 21 (2%) were transferred out to other health facilities and 680 (83%) were still under care. The incidence rate of unfavorable outcomes was 7.9 patients per 100 person years follow-up. Patients with a history of injecting drug use, with a history of lost to follow-up, with a higher baseline viral load and who had received didanosine and abacavir had a higher risk of unfavorable outcomes. Patients with higher baseline C4 counts, those having taken first-line ART at a private clinic, receiving ART at decentralized sites and taking zidovudine and lamivudine had a lower risk of unfavorable outcomes. Conclusions: Long-term outcomes of patients on second-line ART were relatively good in this cohort. Virological failure was relatively low, possibly because of lack of viral load testing. No patient who failed on second-line ART was switched to third-line treatment. The National HIV/AIDS Program should consider making routine viral load monitoring and third-line ART drugs

  16. The Impact of Treatment Preferences in Second-Line Chemotherapy on the Prognosis of HER2-Negative Metastatic Breast Cancer.

    PubMed

    Mukai, Hirofumi; Hagiwara, Yasuhiro; Imi, Kentaro; Isaka, Hirotsugu; Watanabe, Kenichi; Matsuyama, Yutaka

    2017-08-24

    We assessed the impact of treatment preferences in second-line chemotherapy on breast cancer prognosis using the SELECT BC study. The SELECT BC study was performed in patients with HER2-negative metastatic breast cancer treated with initial chemotherapy. From these patients, 618 were assigned to 2 groups (S-1 group, 309; taxane group, 309). The S-1 and taxane groups were each subdivided into 3 groups: crossover group, protocol-recommended group, and other group, and the analysis of overall survival (OS) was performed using Cox regression with inverse probability weighting, to adjust for postrandomization confounding. In the taxane group, the OS of the crossover group (39.6 months) was better than that of the protocol-recommended group (35.7 months) and the other chemotherapy group (36.9 months) (vs. the protocol-recommended group, HR 0.72 [95% CI 0.52-0.98], p = 0.037; vs. the other chemotherapy group, HR 0.71 [95% CI 0.43-1.18], p = 0.183). In the S-1 group, there was no statistically significant difference in OS between the 3 groups. The study of the combination of first-line chemotherapy and second-line chemotherapy showed that S-1 might be recommended as a second-line chemotherapy in patients in whom taxane was the primary chemotherapy. © 2017 The Author(s) Published by S. Karger AG, Basel.

  17. Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

    PubMed Central

    Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

    2012-01-01

    Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

  18. Metronomic capecitabine versus best supportive care as second-line treatment in hepatocellular carcinoma: a retrospective study

    PubMed Central

    Casadei Gardini, Andrea; Foca, Flavia; Scartozzi, Mario; Silvestris, Nicola; Tamburini, Emiliano; Faloppi, Luca; Brunetti, Oronzo; Rudnas, Britt; Pisconti, Salvatore; Valgiusti, Martina; Marisi, Giorgia; Foschi, Francesco Giuseppe; Ercolani, Giorgio; Tassinari, Davide; Cascinu, Stefano; Frassineti, Giovanni Luca

    2017-01-01

    Preliminary studies suggest that capecitabine may be safe and effective in HCC patients. The aim of this study was to retrospectively evaluate the safety and efficacy of metronomic capecitabine as second-line treatment. This multicentric study retrospectively analyzed data of HCC patients unresponsive or intolerant to sorafenib treatment with metronomic capecitabine or best supportive care (BSC).Median progression free survival was 3.1 months in patients treated with capecitabine (95%CI: 2.7–3.5). Median overall survival was 12.0 months (95% CI: 10.7–15.8) in patients receiving capecitabine, while 9.0 months (95% CI: 6.5–13.9) in patients receiving BSC. The result of univariate unweighted Cox regression model shows a 46% reduction in death risk for patients on capecitabine (95%CI: 0.357–0.829; p  =0.005) compared to patients receiving BSC alone. After weighting for potential confounders, death risk remained essentially unaltered (45%; 95%CI: 0.354–0.883; p = 0.013). Metronomic capecitabine seems a safe second-line treatment for HCC patients in terms of management of adverse events, showing a potential anti-tumour activity which needs further evaluation in phase III studies. PMID:28211921

  19. Economic evaluation of sunitinib malate in second-line treatment of metastatic renal cell carcinoma in Finland.

    PubMed

    Purmonen, Timo; Martikainen, Janne A; Soini, Erkki J O; Kataja, Vesa; Vuorinen, Riikka-Liisa; Kellokumpu-Lehtinen, Pirkko-Liisa

    2008-02-01

    Cytokine therapy is currently used as first-line treatment of metastatic renal cell carcinoma (mRCC). Until recently, treatments with proven efficacy after the failure of first-line cytokine therapy were not available. In recent clinical trials, sunitinib has been associated with good response rates in patients with mRCC. The aim of this study was to analyze the cost-effectiveness of sunitinib as second-line therapy for cytokine-refractory mRCC compared with current routine clinical practice in Finland (ie, best supportive care [BSC], including palliative biochemotherapy). A probabilistic decision-analytic model was developed to estimate the cost-effectiveness of sunitinib. Data were gathered from clinical trials, literature sources, and expert opinions, as well as from a local sample (n = 39) from 2 university hospitals in Finland. Clinical experts treating patients with mRCC in Finland provided the information on care practices of prescribing sunitinib. The analysis was conducted from the perspective of the health care payer in Finland. According to estimated incremental cost-effectiveness ratios (ICERs), 1 progression-free month gained cost euro4802 (2005 Euros); 1 life-year gained cost euro30,831; and 1 quality-adjusted life-year (QALY) gained cost euro43,698, compared with BSC, in the treatment of mRCC. The expected mean cost in BSC was euro5543. When parameter uncertainty was considered, the probability of sunitinib being the more cost-effective choice of treatment was ~70% at the willingness-to-pay level of euro45,000/QALY gained. Based on the results of this cost-effectiveness analysis, sunitinib is potentially cost-effective as a second-line treatment of mRCC compared with the treatment currently practiced in Finnish hospitals. The ICER (euro/QALY gained) obtained in the present study was less than the value considered suitable for novel oncology treatments.

  20. Cabazitaxel: a novel second-line treatment for metastatic castration-resistant prostate cancer

    PubMed Central

    Paller, Channing J; Antonarakis, Emmanuel S

    2011-01-01

    Until recently, patients with castration-resistant prostate cancer (CRPC) had limited therapeutic options once they became refractory to docetaxel chemotherapy, and no treatments improved survival. This changed in June 2010 when the Food and Drug Administration (FDA) approved cabazitaxel as a new option for patients with CRPC whose disease progresses during or after docetaxel treatment. For most of these patients, cabazitaxel will now replace mitoxantrone (a drug that was FDA-approved because of its palliative effects) as the treatment of choice for docetaxel-refractory disease. The approval of cabazitaxel was based primarily on the TROPIC trial, a large (n = 755) randomized Phase III study showing an overall median survival benefit of 2.4 months for men with docetaxel-pretreated metastatic CRPC receiving cabazitaxel (with prednisone) compared to mitoxantrone (with prednisone). Cabazitaxel is a novel tubulin-binding taxane that differs from docetaxel because of its poor affinity for P-glycoprotein (P-gp), an ATP-dependent drug efflux pump. Cancer cells that express P-gp become resistant to taxanes, and the effectiveness of docetaxel can be limited by its high substrate affinity for P-gp. Preclinical and early clinical studies show that cabazitaxel retains activity in docetaxel-resistant tumors, and this was confirmed by the TROPIC study. Common adverse events with cabazitaxel include neutropenia (including febrile neutropenia) and diarrhea, while neuropathy was rarely observed. Thus, the combination of cabazitaxel and prednisone is an important new treatment option for men with docetaxel-refractory metastatic CRPC, but this agent should be administered cautiously and with appropriate monitoring (especially in men at high risk of neutropenic complications). PMID:21448449

  1. New chemical treatment options in second-line hepatocellular carcinoma: what to do when sorafenib fails?

    PubMed

    Woo, Hyun Young; Yoo, So Young; Heo, Jeong

    2017-01-01

    There have been no therapies available for patients who experience disease progression after sorafenib treatment. Regorafenib inhibits multiple kinases involved in tumor proliferation and neoangiogenesis, which has produced a survival benefit in hepatocellular carcinoma (HCC) after sorafenib failure. Other active candidate agents are c-Met inhibitors and immune checkpoint inhibitors. Areas covered: This paper presents an updated summary of the preclinical and clinical experience with regorafenib, c-Met inhibitors (tivantinib, cabozantinib and tepotinib), and a checkpoint inhibitor (nivolumab, pembrolizumab) in HCC. The reported data were obtained from abstracts of international conferences and journal articles published up to August 2016 and found in a PubMed search. Expert opinion: Based on favorable data from preclinical and clinical trials, regorafenib, c-Met inhibitor, and checkpoint inhibitors are promising agents for HCC after sorafenib failure. However, further efforts to maximize the survival benefit and minimize adverse events of these drugs in the treatment of HCC are still necessary. Additionally, searching for predictors of good responders could allow these new drugs to be applied in personalized treatments of HCC.

  2. Anti-angiogenic drugs for second-line treatment of NSCLC patients: just new pawns on the chessboard?

    PubMed

    Bronte, Giuseppe; Passiglia, Francesco; Galvano, Antonio; Russo, Antonio

    2016-01-01

    Tumor angiogenesis is one of the main pathways targeted to treat cancer. Bevacizumab added survival benefit when combined with platinum-based chemotherapy in NSCLC. Recently, Phase III trials showed survival benefit when anti-angiogenic drugs are added to docetaxel as second-line treatment for NSCLC. These anti-angiogenic agents include nintedanib and ramucirumab, a tyrosine-kinase inhibitor and a monoclonal antibody, respectively, which target receptors involved in angiogenesis. These studies have some similarities and differences. We propose a new algorithm for treatment sequences in performance status 0-1 patients with non-oncogene-addicted NSCLC type adenocarcinoma. Indeed clearer scientific evidences are available for this subgroup of patients.

  3. Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

    PubMed

    Crespo, C; Izquierdo, G; García-Ruiz, A; Granell, M; Brosa, M

    2014-05-01

    At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  4. Initial Results of Image-Guided Percutaneous Ablation as Second-Line Treatment for Symptomatic Vascular Anomalies

    SciTech Connect

    Thompson, Scott M.; Callstrom, Matthew R. McKusick, Michael A. Woodrum, David A.

    2015-10-15

    PurposeThe purpose of this study was to determine the feasibility, safety, and early effectiveness of percutaneous image-guided ablation as second-line treatment for symptomatic soft-tissue vascular anomalies (VA).Materials and MethodsAn IRB-approved retrospective review was undertaken of all patients who underwent percutaneous image-guided ablation as second-line therapy for treatment of symptomatic soft-tissue VA during the period from 1/1/2008 to 5/20/2014. US/CT- or MRI-guided and monitored cryoablation or MRI-guided and monitored laser ablation was performed. Clinical follow-up began at one-month post-ablation.ResultsEight patients with nine torso or lower extremity VA were treated with US/CT (N = 4) or MRI-guided (N = 2) cryoablation or MRI-guided laser ablation (N = 5) for moderate to severe pain (N = 7) or diffuse bleeding secondary to hemangioma–thrombocytopenia syndrome (N = 1). The median maximal diameter was 9.0 cm (6.5–11.1 cm) and 2.5 cm (2.3–5.3 cm) for VA undergoing cryoablation and laser ablation, respectively. Seven VA were ablated in one session, one VA initially treated with MRI-guided cryoablation for severe pain was re-treated with MRI-guided laser ablation due to persistent moderate pain, and one VA was treated in a planned two-stage session due to large VA size. At an average follow-up of 19.8 months (range 2–62 months), 7 of 7 patients with painful VA reported symptomatic pain relief. There was no recurrence of bleeding at five-year post-ablation in the patient with hemangioma–thrombocytopenia syndrome. There were two minor complications and no major complications.ConclusionImage-guided percutaneous ablation is a feasible, safe, and effective second-line treatment option for symptomatic VA.

  5. Radiological changes following second-line zoledronic acid treatment in breast cancer patients with bone metastases.

    PubMed

    Amir, E; Whyne, C; Freedman, O C; Fralick, M; Kumar, R; Hardisty, M; Clemons, M

    2009-01-01

    Initiation of bisphosphonate therapy in bisphosphonate-naïve patients is known to be associated with radiological changes such as increased bone density in both osteolytic and osteoblastic metastases. It is not known, however, whether switching from a second-generation bisphosphonate to a more potent agent is associated with similar changes. This study aimed to prospectively explore radiological changes, as assessed by thoracolumbar CT scanning, in patients switching from an early generation bisphosphonate (i.e., oral clodronate or intravenous pamidronate) to intravenous zoledronic acid. Patients with progressive bone metastases despite use of an earlier generation bisphosphonate were switched to zoledronic acid as part of a study to evaluate the palliative benefit of this intervention. Quantitative computed tomography (QCT) scanning of the thoracolumbar spine was carried out at baseline, and repeated 4 months after commencing zoledronic acid. The effect of this change of therapy was explored in terms of bone density, as well as volume of osteolytic and osteoblastic disease. Fifteen patients were assessed. Switching of bisphosphonate therapy was associated with a significant increase in bone density, and an increase in osteoblastic volume. There was an insignificant trend towards reduced osteolytic volume. In conclusion, switching from early generation bisphosphonates to a more potent agent is associated with radiological changes similar to those seen when commencing a bisphosphonate in treatment-naïve patients. This is consistent with the observed palliative benefit. The use of QCT may be of benefit in the monitoring of bone metastases.

  6. Second-line Treatments for Advanced Gastric Cancer: A Network Meta-Analysis of Overall Survival Using Parametric Modelling Methods.

    PubMed

    Harvey, Rebecca C

    2017-01-01

    Advanced gastric cancer (AGC) is one of the most common forms of cancer and remains difficult to cure. There is currently no recommended therapy for second-line AGC in the UK despite the availability of various interventions. This paper aims to compare different interventions for treatment of second-line AGC using more complex methods to estimate relative efficacy, fitting various parametric models and to compare results to those published adopting conventional methods of synthesis. Seven studies were identified in an existing literature review evaluating seven comparators, which formed a connected network of evidence. Citations were limited to randomised controlled trials in previously-treated AGC patients. Evidence quality was assessed using the Cochrane Collaboration's tool. Studies were assessed for the availability of Kaplan-Meier curves for overall survival. Individual patient data (IPD) were recreated using digitisation software along with a published algorithm in R. The data were analysed using multi-dimensional network meta-analysis (NMA) methods. A series of parametric models were fitted to the pseudo-IPD. Both fixed and random-effects models were fitted to explore long-term survival prospects based on extrapolation methods and estimated mean survival. Relative efficacy estimates were compared to those previously reported, which utilised conventional NMA methods. Results presented were consistent within findings from other publications and identified ramucirumab plus paclitaxel as the best treatment; however, all the treatments assessed were associated with poor survival prospects with mean survival estimates ranging from 5.0 to 12.7 months. Whilst the approach adopted in this paper does not adjust for differences in trial patient populations and is particularly data-intensive, use of such sophisticated methods of evidence synthesis may be more informative for subsequent cost-effectiveness modelling and may have greater impact when considering an

  7. Chemotherapy or targeted therapy as second-line treatment of advanced gastric cancer. A systematic review and meta-analysis of published studies.

    PubMed

    Iacovelli, Roberto; Pietrantonio, Filippo; Farcomeni, Alessio; Maggi, Claudia; Palazzo, Antonella; Ricchini, Francesca; de Braud, Filippo; Di Bartolomeo, Maria

    2014-01-01

    Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its benefit, less than 60% of patients receive salvage therapy in clinical practice. We performed a systematic review and meta-analysis based on trial data on the role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and Cochrane Library were searched for randomized phase III trials that compared active therapy to best supportive care in advanced gastric cancer. Data extraction was conducted according to the PRISMA statement. Summary HR for OS was calculated using a hierarchical Bayesian model and subgroup analysis was performed based on baseline Eastern Cooperative Oncology Group Performance Status (ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were evaluable for efficacy, 908 were treated in the experimental arms, with chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death was decreased by 18% (HR = 0.82; 95% CI, 0.79-0.85; posterior probability HR≥1: <0.00001) with active therapies. Chemotherapy and ramucirumab were able to decrease this risk by 27% and 22%, respectively. No differences were found between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit was found for chemotherapy with a reduction of the risk of death by 43% and no benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or more a significant reduction of the risk of death by 32% was reported in patients treated with ramucirumab, even if no significant difference was reported between chemotherapy and ramucirumab. This analysis reports that active and available therapies are able to prolong survival in patients with advanced gastric cancer with a different outcome based on initial patient's performance status. New trials based on a better patient stratification are awaited.

  8. A Phase II Study of Gemcitabine, Vincristine, and Cisplatin (Gvp) As Second-Line Treatment for Patients with Advanced Soft Tissue Sarcoma

    PubMed Central

    Luo, Zhiguo; Zhang, Xiaowei; Peng, Wei; Wu, Xianghua; Wang, Huijie; Yu, Hui; Wang, Jialei; Chang, Jianhua; Hong, Xiaonan

    2015-01-01

    Abstract Patients with advanced soft tissue sarcoma (aSTS) typically have a poor prognosis. Patients progressing to doxorubicin-based regimen have limited therapeutic options. Monotherapy with cytotoxic drugs appears to have only modest activity in the second-line setting. The purpose of this phase II study was to prospectively evaluate the safety and efficacy of combination regimen with gemcitabine, vincristine, and cisplatin (GVP) as a salvage treatment for patients with aSTS. Eligible patients were female with 18∼75 years old, and had aSTS that had progressed after 1 prior anthracyclines-based chemotherapy regimen. Patients were treated with 1,000 mg/m2 gemcitabine intravenously (IV) on days 1 and 8, 1.4 mg/m2 (max 2 mg) vincristine IV on day 1 and 25 mg/m2 cisplatin IV on days 1 through 3 every 21 days until disease progression, unacceptable toxicity or up to 6 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), over response rate (ORR) and safety. This trial was registered with www.clinicaltrials.gov (no. NCT01192633). A total of 26 patients with a median age 47 years (21–72) were recruited. ORR was 23.1% [1 complete response and 5 partial responses]. The median PFS and OS were 4.8 (95% CI, 0.1–9.5) months and 15.0 (95% CI, 6.1–23.9) months, respectively. Grade 3/4 hematologic toxicities included neutropenia (34.6%), leukopenia (23.1%), thrombocytopenia (11.5%) and anemia (3.8%). No febrile neutropenia and grade 3/4 non-hematologic toxicities occurred. The most frequent non-hematologic toxicities were nausea/vomiting (50.0%), fatigue (30.8%), and fever (11.5%). We conclude that GVP regimen is effective with a favorable safety profile as the second-line chemotherapy in aSTS patients, which warrants further investigation in a phase III study. PMID:26512574

  9. Phase 2 study of combination SPI-1620 with docetaxel as second-line advanced biliary tract cancer treatment.

    PubMed

    Kim, Richard; Chiorean, E Gabriela; Amin, Manik; Rocha-Lima, Caio Max S; Gandhi, Jitendra; Harris, William P; Song, Tao; Portnoy, David

    2017-07-11

    This multicentre, open-label study evaluated the efficacy and safety of SPI-1620, an analogue of endothelin-1, administered in combination with docetaxel as second-line treatment for patients with advanced biliary tract cancer (ABTC). Eligible patients received continuous cycles of combination therapy with SPI-1620 (11 μg m(-2)) and docetaxel (75 mg m(-2)) intravenously every 3 weeks until disease progression (PD) or intolerable toxicity. Tumour response was evaluated using computed tomography or magnetic resonance imaging every 2 cycles (6 weeks). The primary efficacy end point was progression-free survival (PFS); secondary end points included overall response rate (ORR), duration of response, and overall survival (OS) that were estimated using the Kaplan-Meier method. Of the 30 enrolled patients, 25 patients had qualifying events (PD or death), 1 patient was nonevaluable, and 4 patients were censored at the time of their last tumour assessment. Our primary end point of PFS ⩾5 months was not reached. Median PFS was 2.6 months (95% confidence interval (CI): 1.4-2.8), ranging from 0.7 to 8.4 months. The ORR was 10.3% (95% CI: 0.02-0.27). Eleven additional patients achieved stable disease. The OS was 4.87 months. The most common grade 3-4 toxicities were febrile neutropenia and neutropenia. The addition of docetaxel to SPI-1620 in second-line ABTC did not meet the pre-specified primary end point of PFS ⩾5 months in unselected patient population.

  10. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

    PubMed

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

  11. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    PubMed Central

    Trojan, Jörg; Waidmann, Oliver

    2016-01-01

    Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

  12. Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies.

    PubMed

    Khellaf, Mehdi; Chabrol, Amèlie; Mahevas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

    2014-02-01

    Treatment of patients with lupus-associated thrombocytopenia (SLE-ITP) is not standardized. We report data on efficacy and safety of hydroxychloroquine (HCQ) in this setting and in ITP patients with positive antinuclear antibodies (ANA) without definite SLE. Inclusion criteria were: definite diagnosis of ITP with a platelet count (PLT) <50 × 10(9) /L, ANA ≥ 1/160 on Hep2 cells with or without a definite diagnosis of SLE, and no sustained response to at least one previous treatment-line and treatment with HCQ. Response criteria were Complete Response (CR) for PLT ≥ 100 × 10(9) /L and Response (R) for PLT ≥30 × 10(9) /L and at least twice the initial value. Forty patients (32 females) with a mean age of 35 ± 17 years and PLT at ITP diagnosis of 14 ± 13 × 10(9) /L were analyzed. Twelve (30%) patients had a SLE-ITP, 28 patients had only positive ANA. All the patients failed to respond to oral prednisone with a median of two treatment-lines (1-5) before HCQ which was initially given in combination with another ITP treatment in 36 patients. Overall response rate was 60% (24/40) including 18 lasting CR and six lasting R maintained with a median follow-up of 64 months (6-146), in ¾ of cases with only HCQ and no concomitant ITP treatment. The response rate (CR+R) was higher in the SLE group vs ANA-positive group (83% vs 50%, P < 0.05). No patient stopped HCQ because of a side-effect. HCQ appears to be a safe and effective second line treatment for patients with SLE-ITP or ITP and high titer of ANA. This trial was registered at www.clinicaltrials.gov as # NCT01549184.

  13. A phase II study of carboplatin and vinorelbine as second-line treatment for advanced breast cancer.

    PubMed Central

    Iaffaioli, R. V.; Tortoriello, A.; Facchini, G.; Santangelo, M.; De Sena, G.; Gesue, G.; Bucci, L.; Scaramellino, G.; Anastasio, E.; Finizio, A.

    1995-01-01

    Forty-one patients with advanced breast cancer were given carboplatin and vinorelbine as second-line therapy. Overall objective response rate was 46% (95% confidence interval 26-56%). Myelotoxicity was the most frequently observed toxic effect; grade III-IV leucopenia occurred in 46% of the patients. Our regimen is active as second-line chemotherapy for advanced breast cancer and warrants further evaluation. PMID:7577478

  14. Patients rank toxicity against progression free survival in second-line treatment of advanced renal cell carcinoma.

    PubMed

    Wong, Michael K; Mohamed, Ateesha F; Hauber, A Brett; Yang, Jui-Chen; Liu, Zhimei; Rogerio, Jaqueline; Garay, Carlos A

    2012-01-01

    The aims of this study were to quantify and contrast patient preferences between second-line advanced renal cell carcinoma (RCC) medication profiles and their associated benefits and toxicities, and to help frame the doctor-patient discussion about selecting appropriate RCC therapies. Adult residents of the US with a diagnosis of RCC completed a Web-enabled choice-format conjoint survey consisting of a series of 10 treatment-choice questions, each of which included a pair of hypothetical RCC medication profiles. Each profile was described by various medication attributes (features or outcomes) with varying levels. The attributes included efficacy (progression-free survival [PFS]), tolerability (fatigue, stomach problems, mucositis or stomatitis, hand-foot syndrome [HFS]), serious but rare adverse events (pneumonitis, hepatic impairment), and mode of administration. Treatment-choice questions were based on an experimental design with known statistical properties. Random-parameters logit regression was used to estimate relative preference weights for each attribute level. Benefit equivalent measures (additional months of PFS in exchange for toxicities) were also calculated. Of the 272 patients who completed the survey, the majority were female (53%), white (92%), and had at least a college degree (66%). The mean age was 57 years (standard deviation: 10 years). Over the range of attributes and attribute levels included in the survey, PFS was the most important attribute, followed by fatigue, stomach problems, hepatic impairment, mucositis or stomatitis, HFS, pneumonitis, and mode of administration. To reduce severe fatigue to mild-to-moderate fatigue, patients on average would be willing to forego 4.4 months of PFS. To reduce hepatic impairment risk from 0.5% to 0.0%, patients on average would be willing to forego 1.0 month of PFS. The main study limitation was that patients answered hypothetical treatment-choice questions. This study provides information to

  15. Transarterial Chemoembolization With Cisplatin as Second-Line Treatment for Hepatocellular Carcinoma Unresponsive to Chemoembolization With Epirubicin-Lipiodol Emulsion

    SciTech Connect

    Maeda, Noboru Osuga, Keigo; Higashihara, Hiroki; Tomoda, Kaname; Mikami, Koji; Nakazawa, Tetsuro; Nakamura, Hironobu; Tomiyama, Noriyuki

    2012-02-15

    Purpose: The purpose of this retrospective study was to investigate the efficacy of transarterial chemoembolization (TACE) using cisplatin as a second-line treatment for advanced hepatocellular carcinoma (HCC) unresponsive to TACE using epirubicin-Lipiodol emulsion at our institution. Materials and Methods: Between January 2006 and March 2009, 51 patients with unresectable HCC underwent TACE using cisplatin. All patients had shown persistent viable tumor or tumor progression after at least 2 sessions of TACE using epirubicin-Lipiodol emulsion. TACE procedures consisted of arterial injection of a mixture of Lipiodol and cisplatin (30-100 mg [mean 57 {+-} 21]) (n = 29) or arterial infusion of cisplatin (30-100 mg [mean 87 {+-} 19]) solution (n = 22) followed by injection of 1-mm porous gelatin particles. Early tumor response was assessed by contrast-enhanced computed tomography (CT) according to Response Evaluation Criteria in Solid Tumors (RECIST) and European Association for the Study of the Liver (EASL) criteria. Overall survival and progression-free survival was calculated using the Kaplan-Meier method. Toxicity was assessed according to NCI-CTCAE version 3 criteria. Results: Response rates were 11.8 and 27.5% by RECIST and EASL criteria, respectively. Overall survival rates were 61.9, 48.2, and 28.9% at 1, 2, and 3 years, respectively, and the median survival time was 15.4 months. Progression-free survival rate was 35.2% at 1 year, and median progression-free survival time was 3.1 months. No major complications were observed, and the occurrence of postembolization syndrome was minimal. Grade 3 to 4 toxicities included thrombocytopenia (5.8%), increased aspartate aminotransferase (AST) level (35.3%), and increased alanine aminotransferase (ALT) level (23.5%). Conclusions: witching the TACE anticancer drug from epirubicin to cisplatin might be the feasible option for advanced HCC, even when considered resistant to the initial form of TACE.

  16. Therapeutic plasma exchange: a second-line treatment for brodifacoum poisoning following an anaphylactoid reaction to vitamin K.

    PubMed

    Deng, Ying; Qiu, Li

    2017-01-01

    Vitamin K1 is the first-line therapy to brodifacoum poisoning. Anaphylactoid reactions may occur anytime during intravenous administration of vitamin K1 injection. Vitamin K1 must be ceased when anaphylactoid reactions emerge, and therapeutic plasma exchange could be a second-line option.

  17. Cabazitaxel for the second-line treatment of metastatic hormone-refractory prostate cancer: a NICE single technology appraisal.

    PubMed

    Kearns, Ben; Lloyd Jones, Myfanwy; Stevenson, Matt; Littlewood, Chris

    2013-06-01

    The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of cabazitaxel (Jevtana®, sanofi-aventis, UK) to submit evidence of its clinical and cost effectiveness for the second-line treatment of metastatic hormone-refractory prostate cancer (mHRPC). The School of Health and Related Research Technology Appraisal Group (ScHARR-TAG) at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer's submission to NICE. Clinical evidence was derived from a multinational randomized open-label phase III trial of cabazitaxel plus prednisone or prednisolone in men with mHRPC that had progressed during or following treatment with docetaxel. The comparator was mitoxantrone plus prednisone or prednisolone. Use of cabazitaxel was associated with a statistically significant improvement in overall survival, median progression-free survival and time to tumour progression. However, it was also associated with an increased incidence of adverse events such as neutropenia. Utility data were based on interim results from the early access programme for cabazitaxel. Data were only available for a small number of patients with stable disease, resulting in great uncertainty as to the effect of cabazitaxel on quality of life. For their economic evaluation, the manufacturer estimated that the use of cabazitaxel was associated with an incremental cost of £74,908 per QALY gained. However, the ERG disagreed with the manufacturer over two key methodological points. The first concerned modelling and extrapolating survival; the second point was concerned with the choice of patient population. The ERG altered the manufacturer's evaluation to take into account these two points of disagreement. The resulting cost per QALY gained was £82,950. The NICE Appraisal Committee believed the analysis

  18. Successful Multidisciplinary Treatment with Secondary Metastatic Liver Resection after Downsizing by Palliative Second-Line Treatment of Colorectal Cancer: A Curative Option

    PubMed Central

    Wein, Axel; Siebler, Jürgen; Goertz, Ruediger; Wolff, Kerstin; Ostermeier, Nicola; Busse, Dagmar; Kremer, Andreas E.; Koch, Franz; Hagel, Alexander; Farnbacher, Michael; Kammerer, Ferdinand J.; Neurath, Markus F.; Gruetzmann, Robert

    2016-01-01

    Introduction The prognostic outcome following progression after palliative first-line treatment for patients suffering from metastatic colorectal adenocarcinoma is generally poor. Long-term relapse-free survival with palliative second-line treatment may be achieved in only a limited number of individual cases. Case Report A 37-year-old patient presented with bilobar liver metastases of colon cancer confirmed by histology with wild-type K-RAS (exon 2). Due to progressive disease after eight cycles of first-line therapy with FOLFIRI plus cetuximab, second-line chemotherapy with modified FOLFOX4 (mFOLFOX4) plus bevacizumab was initiated. During four cycles of mFOLFOX4 plus bevacizumab (2 months), no higher-grade toxicity occurred. Liver MRI with contrast medium revealed downsizing of the segment II/III metastases, as well as regressive, small, faint, hardly definable lesions in segments VI and IVb. The interdisciplinary tumor board of the University of Erlangen thus decided to perform resection of the liver metastases. Segments II and III were resected, and the liver metastases in segments IVa and VI were excised (R0). Histopathology confirmed three of the R0-resected metastases to be completely necrotic, with residual scarring. As perioperative therapy, four additional cycles of mFOLFOX4 plus bevacizumab were administered postoperatively. No higher-grade toxicity was observed. Three years after the initial diagnosis, the patient is relapse free, professionally fully reintegrated, and has an excellent performance status. Conclusion Patients suffering from metastatic colorectal cancer may benefit from multidisciplinary treatment with secondary metastatic liver resection after downsizing by palliative second-line treatment. In individual cases, patients may even have a curative treatment option, provided that close interdisciplinary collaboration exists. PMID:27489542

  19. Second-line therapy in diffuse large B-cell lymphoma (DLBCL): treatment patterns and outcomes in older patients receiving outpatient chemotherapy.

    PubMed

    Danese, Mark D; Griffiths, Robert I; Gleeson, Michelle L; Dalvi, Tapashi; Li, Jingyi; Mikhael, Joseph R; Deeter, Robert; Dreyling, Martin

    2017-05-01

    Using SEER-Medicare linked data we identified elderly patients diagnosed with diffuse large B-cell lymphoma (DLBCL) between January 2000 and December 2007 who received second-line outpatient chemotherapy for relapsed or refractory disease. Second-line regimens were classified into three mutually exclusive groups: aggressive, conventional, and palliative. Of the 632 (426 relapsed, 206 refractory) patients in the cohort, 27.8% received aggressive second-line therapy, 39.1% received conventional therapy, and 33.1% received palliative therapy. There were no differences in survival by type of therapy received, either for relapsed or refractory patients, although the patient risk profile differed significantly. However, duration of remission, male gender, and anemia at diagnosis were important predictors in relapsed patients, and male gender, B-symptoms, comorbidity burden, and poverty status were important predictors in refractory patients. Survival in elderly patients receiving second-line therapy remains poor, and the 24-month cost of all care exceeds $97,000. Patients would benefit from improved treatment options.

  20. Pre-treatment prediction of chemoresistance in second-line chemotherapy of ovarian carcinoma: value of serological tumor marker determination (tetranectin, YKL-40, CASA, CA 125).

    PubMed

    Gronlund, B; Høgdall, E V S; Christensen, I J; Johansen, J S; Nørgaard-Pedersen, B; Engelholm, S A; Høgdall, C

    2006-01-01

    To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients. From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed. At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2-0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0-3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2-2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66-0.91; p=0.001). Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.

  1. HIV-1 Drug Resistance and Second-line Treatment in Children Randomized to Switch at Low versus Higher RNA Thresholds

    PubMed Central

    Harrison, Linda; Melvin, Ann; Fiscus, Susan; Saidi, Yacine; Nastouli, Eleni; Harper, Lynda; Compagnucci, Alexandra; Babiker, Abdel; McKinney, Ross; Gibb, Diana; Tudor-Williams, Gareth

    2015-01-01

    Background The PENPACT-1 trial compared virologic thresholds to determine when to switch to second-line antiretroviral therapy (ART). Using PENPACT-1 data, we aimed to describe HIV-1 drug resistance accumulation on first-line ART by virologic threshold. Methods PENPACT-1 had a 2x2 factorial design, randomizing HIV-infected children to start protease inhibitor (PI) versus non-nucleoside reverse transcriptase inhibitor (NNRTI) based ART, and switch at a 1000c/ml versus 30000c/ml threshold. Switch-criteria were: not achieving the threshold by week 24, confirmed rebound above the threshold thereafter, or CDC-C event. Resistance tests were performed on samples ≥1000c/ml before switch, re-suppression and at 4-year/trial-end. Results Sixty-seven children started PI-based ART and were randomized to switch at 1000c/ml (PI-1000), 64 PIs and 30000c/ml (PI-30000), 67 NNRTIs and 1000c/ml (NNRTI-1000), and 65 NNRTI and 30000c/ml (NNRTI-30000). Ninety-four (36%) children reached the 1000c/ml switch-criteria during 5 years follow-up. In 30000c/ml threshold arms, median time from 1000c/ml to 30000c/ml switch-criteria was 58 (PI) versus 80 (NNRTI) weeks (P=0.81). In NNRTI-30000 more NRTI resistance mutations accumulated than other groups. NNRTI mutations were selected before switching at 1000c/ml (23% NNRTI-1000, 27% NNRTI-30000). Sixty-two children started abacavir+lamivudine, 166 lamivudine+zidovudine or stavudine, and 35 other NRTIs. The abacavir+lamivudine group acquired fewest NRTI mutations. Of 60 switched to second-line, 79% PI-1000, 63% PI-30000, 64% NNRTI-1000 and 100% NNRTI-30000 were <400c/ml 24 weeks later. Conclusion Children on first-line NNRTI-based ART who were randomized to switch at a higher virologic threshold developed the most resistance, yet re-suppressed on second-line. An abacavir+lamivudine NRTI combination seemed protective against development of NRTI resistance. PMID:26322666

  2. Erlotinib or docetaxel for second-line treatment of non-small cell lung cancer: a real-world cost-effectiveness analysis.

    PubMed

    Cromwell, Ian; van der Hoek, Kimberly; Melosky, Barbara; Peacock, Stuart

    2011-12-01

    Erlotinib was recently approved in British Columbia (BC) as a second-line treatment for advanced NSCLC. A cost-effectiveness analysis was conducted which compares costs and effectiveness in patients who received second-line erlotinib with those in patients who received docetaxel. In a population of patients who have been treated with drugs (either erlotinib or docetaxel) for advanced NSCLC, overall survival (OS), progression-free survival (PFS), and probability of survival 1 year after beginning of second-line treatment (1YS) were determined using Kaplan-Meier and Cox proportional hazard analysis, as well as χ test. Costs were collected retrospectively from the perspective of the BC health care system. Incremental mean OS was 1 day, and incremental mean cost was $2891. Neither costs nor effectiveness were statistically significantly different between groups. PFS and 1YS were also nonsignificantly different. Cox proportional hazard models were used to evaluate multivariate confounding. Erlotinib and docetaxel are statistically equivalent in terms of treatment cost and overall survival. As treatment practice patterns change, docetaxel may become more frequently prescribed. Therefore, the choice of whether to use erlotinib or docetaxel should be based on factors relating to patient preference rather than costs or effectiveness.

  3. Treatment of multidrug-resistant tuberculosis during pregnancy: long-term follow-up of 6 children with intrauterine exposure to second-line agents.

    PubMed

    Drobac, Peter C; del Castillo, Hernan; Sweetland, Annika; Anca, Genaro; Joseph, J Keith; Furin, Jennifer; Shin, Sonya

    2005-06-01

    Treatment of gestational multidrug-resistant tuberculosis (MDR-TB) is controversial. We describe follow-up of 6 children exposed to second-line antituberculous agents in utero. Each child (average age, 3.7 years) underwent comprehensive clinical evaluation. One child had MDR-TB diagnosed. There was no evidence of significant late-presentation toxicity among the children. The results suggest that aggressive management of gestational MDR-TB may benefit both mother and child.

  4. Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry.

    PubMed

    Monti, Sara; Klersy, Catherine; Gorla, Roberto; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola; Pellerito, Raffaele; Fusaro, Enrico; Paolazzi, Giuseppe; Rocchetta, Pier Andrea; Favalli, Ennio Giulio; Marchesoni, Antonio; Caporali, Roberto

    2017-04-01

    According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician's preference. We analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into "first-" and "second-line" bDMARD. We included 1910 patients (first line n = 1264, second line n = 646). Age was higher in ABA or TCZ vs TNFi treated patients (p < 0.0001). Positive latent tuberculosis screening was associated with first-line ABA (p = 0.002). Methotrexate (MTX) combination therapy was lower in the TCZ group (p = 0.02). The type (dyslipidemia, hypertension, pulmonary disease) and the number of comorbidities influenced the choice towards ABA (p = 0.01). Multinomial logistic regression demonstrated that a second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi. TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA. In real life, higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. ABA was preferred in case of suspension of previous treatments due to AE. After failing a first-line TNFi, swapping to a different mechanism of action is more common.

  5. Using Lopinavir Concentrations in Hair Samples to Assess Treatment Outcomes on Second-Line Regimens Among Asian Children

    PubMed Central

    Prasitsuebsai, Wasana; Kerr, Stephen J.; Truong, Khanh Huu; Ananworanich, Jintanat; Do, Viet Chau; Nguyen, Lam Van; Kurniati, Nia; Kosalaraksa, Pope; Sudjaritruk, Tavitiya; Chokephaibulkit, Kulkanya; Thammajaruk, Narukjaporn; Singtoroj, Thida; Teeraananchai, Sirinya; Horng, Howard; Bacchetti, Peter; Gandhi, Monica

    2015-01-01

    Abstract We conducted a prospective monitoring study to determine whether antiretroviral (ARV) levels in hair of Asian children on second-line protease inhibitor-based ARV therapy (ART) are associated with virologic failure (VF), compared to plasma drug levels and self-reported adherence. HIV-infected Asian children on second-line ART regimens were enrolled into a longitudinal cohort. Traditional adherence measures, plasma, and hair samples were collected 24 weeks after study enrollment. Hair ARV levels were determined via liquid chromatography/tandem mass spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were female; the median [interquartile range (IQR)] age was 10.3 (7.9–13.3) years. The median CD4% was 26% (IQR 21.7–32.1%) and the median CD4 cell count 754 (IQR 596–1,013) cells/mm3. The median duration of lopinavir-based ART prior to week 24 of the study was 2.9 (IQR 1.6–4.2) years. Adherence was >95% in 91% (135/148) by visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair concentrations were 5.43 (IQR 3.21–9.01) ng/mg in children with HIV RNA >1,000 copies/ml and 9.96 (IQR 6.51–12.31) ng/mg in children with HIV RNA <1,000 copies/ml (p = 0.003). Plasma trough and lopinavir hair concentrations were not statistically significantly correlated (Pearson's correlation coefficient 0.20; p = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly associated with virologic success (odds ratios ≥4.0, overall p = 0.02), while self-reported adherence, pill count, and plasma lopinavir levels were not. Based on this first report of hair ARV concentrations and virologic outcomes in children, ARV hair concentrations, representing longer-term adherence, may be useful to identify children at risk for VF. PMID:26200586

  6. Using Lopinavir Concentrations in Hair Samples to Assess Treatment Outcomes on Second-Line Regimens Among Asian Children.

    PubMed

    Prasitsuebsai, Wasana; Kerr, Stephen J; Truong, Khanh Huu; Ananworanich, Jintanat; Do, Viet Chau; Nguyen, Lam Van; Kurniati, Nia; Kosalaraksa, Pope; Sudjaritruk, Tavitiya; Chokephaibulkit, Kulkanya; Thammajaruk, Narukjaporn; Singtoroj, Thida; Teeraananchai, Sirinya; Horng, Howard; Bacchetti, Peter; Gandhi, Monica; Sohn, Annette H

    2015-10-01

    We conducted a prospective monitoring study to determine whether antiretroviral (ARV) levels in hair of Asian children on second-line protease inhibitor-based ARV therapy (ART) are associated with virologic failure (VF), compared to plasma drug levels and self-reported adherence. HIV-infected Asian children on second-line ART regimens were enrolled into a longitudinal cohort. Traditional adherence measures, plasma, and hair samples were collected 24 weeks after study enrollment. Hair ARV levels were determined via liquid chromatography/tandem mass spectrometry. Among 149 children on lopinavir/ritonavir-based regimens, 47% were female; the median [interquartile range (IQR)] age was 10.3 (7.9-13.3) years. The median CD4% was 26% (IQR 21.7-32.1%) and the median CD4 cell count 754 (IQR 596-1,013) cells/mm(3). The median duration of lopinavir-based ART prior to week 24 of the study was 2.9 (IQR 1.6-4.2) years. Adherence was >95% in 91% (135/148) by visual analogue scale and 89% (129/145) by pill count. The median lopinavir hair concentrations were 5.43 (IQR 3.21-9.01) ng/mg in children with HIV RNA >1,000 copies/ml and 9.96 (IQR 6.51-12.31) ng/mg in children with HIV RNA <1,000 copies/ml (p = 0.003). Plasma trough and lopinavir hair concentrations were not statistically significantly correlated (Pearson's correlation coefficient 0.20; p = 0.13). Increasing lopinavir hair concentrations in quartiles were strongly associated with virologic success (odds ratios ≥4.0, overall p = 0.02), while self-reported adherence, pill count, and plasma lopinavir levels were not. Based on this first report of hair ARV concentrations and virologic outcomes in children, ARV hair concentrations, representing longer-term adherence, may be useful to identify children at risk for VF.

  7. Impact of insulin sensitivity, beta-cell function and glycaemic control on initiation of second-line glucose-lowering treatment in newly diagnosed type 2 diabetes.

    PubMed

    Rathmann, Wolfgang; Strassburger, Klaus; Bongaerts, Brenda; Bobrov, Pavel; Kuss, Oliver; Müssig, Karsten; Markgraf, Daniel F; Szendroedi, Julia; Herder, Christian; Roden, Michael

    2017-06-01

    The aim of this study was to investigate whether insulin sensitivity, beta-cell function or glycaemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes. Type 2 diabetes patients (n = 138) undergoing initial metformin monotherapy (age [mean ± SD], 52 ± 10 years; 67% males; BMI, 32 ± 6 kg/m(2) ) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under care of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp, M value; i.v. glucose tolerance test, incremental C-peptide area under the curve0-60 minutes, CP iAUC). The associations of baseline M value, CP iAUC, fasting glucose and HbA1c with time to second-line therapy were assessed using parametric survival analysis, accounting for interval-censoring. Second-line treatment was initiated in 26% of newly diagnosed type 2 diabetes patients within the first 3.3 years after diagnosis, using mostly DPP-4 inhibitors or GLP-1 receptor agonists (64%). In age-, sex- and BMI-adjusted survival models, higher baseline HbA1c and fasting glucose values were associated with earlier treatment intensification. Lower baseline M value and C-peptide secretion (CP iAUC) were also related to an earlier initiation of second-line treatment. In the best multivariable model, baseline HbA1c ≥ 7% (hazard ratio, HR; 95% CI: 3.18; 1.35-7.50) and fasting glucose ≥140 mg/dL (HR, 2.45; 95% CI, 1.04-5.78) were associated with shorter time to second-line therapy, adjusting for age, sex and BMI. Baseline hyperglycaemia is a strong predictor of requirement of early intensification of glucose-lowering therapy in newly diagnosed type 2 diabetes. © 2017 John Wiley & Sons Ltd.

  8. Second-Line Antiretroviral Therapy in a Workplace and Community-Based Treatment Programme in South Africa: Determinants of Virological Outcome

    PubMed Central

    Johnston, Victoria; Fielding, Katherine; Charalambous, Salome; Mampho, Mildred; Churchyard, Gavin; Phillips, Andrew; Grant, Alison D.

    2012-01-01

    Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART. Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ≥400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios. Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400. Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both

  9. Determination of MIC Breakpoints for Second-Line Drugs Associated with Clinical Outcomes in Multidrug-Resistant Tuberculosis Treatment in China.

    PubMed

    Zheng, Xubin; Zheng, Rongrong; Hu, Yi; Werngren, Jim; Forsman, Lina Davies; Mansjö, Mikael; Xu, Biao; Hoffner, Sven

    2016-08-01

    Our study aims to identify the clinical breakpoints (CBPs) of second-line drugs (SLDs) above which standard therapy fails in order to improve multidrug-resistant tuberculosis (MDR-TB) treatment. MICs of SLDs were determined for M. tuberculosis isolates cultured from 207 MDR-TB patients in a prospective cohort study in China between January 2010 and December 2012. Classification and regression tree (CART) analysis was used to identify the CBPs predictive of treatment outcome. Of the 207 MDR-TB isolates included in the present study, the proportion of isolates above the critical concentration recommended by WHO ranged from 5.3% in pyrazinamide to 62.8% in amikacin. By selecting pyrazinamide as the primary node (CBP, 18.75 mg/liter), 72.1% of sputum culture conversions at month four could be predicted. As for treatment outcome, pyrazinamide (CBP, 37.5 mg/liter) was selected as the primary node to predict 89% of the treatment success, followed by ofloxacin (CBP, 3 mg/liter), improving the predictive capacity of the primary node by 10.6%. Adjusted by identified confounders, the CART-derived pyrazinamide CBP remained the strongest predictor in the model of treatment outcome. Our findings indicate that the critical breakpoints of some second-line drugs and PZA need to be reconsidered in order to better indicate MDR-TB treatment outcome.

  10. Predictors of treatment failure on second-line antiretroviral therapy among adults in northwest Ethiopia: a multicentre retrospective follow-up study

    PubMed Central

    Tsegaye, Adino Tesfahun; Wubshet, Mamo; Awoke, Tadesse; Addis Alene, Kefyalew

    2016-01-01

    Background The number of patients using second-line antiretroviral therapy (ART) has increased over time. In Ethiopia, 1.5% of HIV infected patients on ART are using a second-line regimen and little is known about its effect in this setting. Objective To estimate the rate and predictors of treatment failure on second-line ART among adults living with HIV in northwest Ethiopia. Setting An institution-based retrospective follow-up study was conducted at three tertiary hospitals in northwest Ethiopia from March to May 2015. Participants 356 adult patients participated and 198 (55.6%) were males. Individuals who were on second-line ART for at least 6 months of treatment were included and the data were collected by reviewing their records. Primary outcome measure The primary outcome was treatment failure defined as immunological failure, clinical failure, death, or lost to follow-up. To assess our outcome, we used the definitions of the WHO 2010 guideline. Result The mean±SD age of participants at switch was 36±8.9 years. The incidence rate of failure was 61.7/1000 person years. The probability of failure at the end of 12 and 24 months were 5.6% and 13.6%, respectively. Out of 67 total failures, 42 (62.7%) occurred in the first 2 years. The significant predictors of failure were found to be: WHO clinical stage IV at switch (adjusted HR (AHR) 2.1, 95% CI 1.1 to 4.1); CD4 count <100 cells/mm3 at switch (AHR 2.0, 95% CI 1.2 to 3.5); and weight change (AHR 0.92, 95% CI 0.88 to 0.95). Conclusions The rate of treatment failure was highest during the first 2 years of treatment. WHO clinical stage, CD4 count at switch, and change in weight were found to be predictors of treatment failure. PMID:27932339

  11. Long-term follow up Helicobacter Pylori reinfection rate after second-line treatment: bismuth-containing quadruple therapy versus moxifloxacin-based triple therapy

    PubMed Central

    2013-01-01

    Background The increasing trend of antibiotic resistance requires effective second-line Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori after second-line treatment that would determine the long-term follow up effect of the rescue therapy. Methods A total of 648 patients who had failed previous H. pylori eradication on standard triple therapy were randomized into two regimens: 1, esomeprazole (20 mg b.i.d), tripotassium dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (20 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, H. pylori tests were performed with 13C urea breath test or invasive tests. In patients who maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. For the evaluation of risk factors of reinfection, gender, age, clinical diagnosis, histological atrophic gastritis or intestinal metaplasia were analyzed. Results The recrudescence rate of the EBMT was 1.7% and of the MEA group 3.3% (p = 0.67). The annual reinfection rate of H. pylori of EBMT was found to be 4.45% and the MEA group 6.46%. Univariate analysis (Log-rank test) showed no association with any clinical risk factor for reinfection. Conclusions The long-term reinfection rate of H. pylori stayed low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy; thus reinfection cannot affect the choice of second-line treatment. Trial registration Clinical Trial Registration Number NCT01792700 PMID:24050512

  12. Second-line therapy with levofloxacin after failure of treatment to eradicate helicobacter pylori infection: time trends in a Spanish Multicenter Study of 1000 patients.

    PubMed

    Gisbert, Javier P; Pérez-Aisa, Angeles; Bermejo, Fernando; Castro-Fernández, Manuel; Almela, Pedro; Barrio, Jesús; Cosme, Angel; Modolell, Inés; Bory, Felipe; Fernández-Bermejo, Miguel; Rodrigo, Luis; Ortuño, Jesús; Sánchez-Pobre, Pilar; Khorrami, Sam; Franco, Alejandro; Tomas, Albert; Guerra, Iván; Lamas, Eloisa; Ponce, Julio; Calvet, Xavier

    2013-02-01

    Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing. To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time. Prospective multicenter study. In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed. Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days. Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%). Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

  13. Efficacy of Second-line Tyrosine Kinase Inhibitors in the Treatment of Metastatic Advanced Non-small-cell Lung Cancer Harboring Exon 19 and 21 EGFR Mutations

    PubMed Central

    Zheng, Zhen; Jin, Xiance; Lin, Baochai; Su, Huafang; Chen, Hanbin; Fei, Shaoran; Zhao, Lihao; Deng, Xia; Xie, Deyao; Xie, Congying

    2017-01-01

    Background: Although superior clinical benefits of first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported with different sensitivity, the sensitivity of second-line TKIs in NSCLC patients with different EFGR mutations was unknown. The purpose of this study is to investigate the clinical outcome of second-line EGFR-TKIs in the treatment of NSCLC patients according to different EGFR genotypes. Methods: The treatment outcomes of 166 NSCLC patients with different EGFR mutations treated by second-line TKIs were retrospectively reviewed. The efficacy was evaluated with Pearson chi-square or Fisher's exact tests, Log-rank test and Cox proportional hazards model. Results: The disease control rate (DCR) and objective response rate (ORR) of enrolled NSCLC patients were 77.7% and 11.4%, respectively. The exon 19 deletion group had a significantly longer median progression-free survival (PFS) (6.7 vs. 4.5 months, P=0.002) and overall survival (OS) (13.7 vs. 11.7 months, P=0.02) compared with the exon 19 L858R mutation group for NSCLC patients, as well for patients with brain metastasis [PFS: (6.7 vs. 3.9 months, p<0.001), OS: (13.7 vs. 7.9 months, p=0.006)]. No significant difference on PFS and OS was observed between exon 19 deletion and L858R mutation group for patients with bone metastasis. EGFR genotype and ECOG PS were independent predictors of PFS. Never smoking, exon 19 deletion, EGOC PS (0-1) and no brain metastasis were correlated with longer OS. No significant difference on side effect between exon 19 and 21 mutation group was observed. Conclusions: NSCLC patients harboring exon 19 deletion achieved better PFS and OS than those with L858R mutation, indicating that EGFR mutation is a significant prognostic factor for advanced NSCLC patients with and without brain metastasis receiving second-line EGFR-TKIs treatment. PMID:28367239

  14. Second-line treatment with intravenous gemcitabine and oral etoposide in platinum-resistant advanced ovarian cancer patients: results of a phase II study.

    PubMed

    Bruzzone, M; Centurioni, M G; Giglione, P; Gualco, M; Merlo, D F; Miglietta, L; Cosso, M; Giannelli, F; Cristoforoni, P; Ferrarini, M

    2011-01-01

    The outcome of advanced ovarian cancer patients has not significantly improved since the introduction of platinum. One of the major reasons for this failure is the lack of an effective second-line treatment. In this phase II trial we tested the combination of gemcitabine and etoposide in 2 different groups of patients. Group 1 consisted of patients showing disease progression or relapse within 6 months of first-line platinum-based chemotherapy. Group 2 comprised heavily pretreated patients showing progression during the last chemotherapy attempt. Thirty-four patients were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m(2) on days 1 and 8 and etoposide was administered orally at 100 mg/day on days 8-12 for 6 courses. Eighteen patients (52.9%) had an objective response and the median duration of the response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good patient compliance. In 5 patients the treatment had to be delayed and in only 2 patients it was discontinued. The combination of gemcitabine and oral etoposide seems to be a safe and effective second-line treatment for platinum-resistant ovarian cancer patients. Additional data on larger series are warranted to better define the activity of this combination regimen. Copyright © 2011 S. Karger AG, Basel.

  15. Salvage palmar fasciectomy after initial treatment with collagenase clostridium histolyticum.

    PubMed

    Eberlin, Kyle R; Kobraei, Edward M; Nyame, Theodore T; Bloom, Jacob M; Upton, Joseph

    2015-06-01

    Collagenase clostridium histolyticum was approved for clinical use in 2010 and has become an accepted treatment modality for Dupuytren's contracture. Because longitudinal experience with injectable collagenase remains limited, the effect of treatment on future surgery is not well defined. A retrospective review of the senior author's practice from February of 2010 through March of 2014 was performed. Eleven patients were identified who had digital or palmar fasciectomy after at least one previous injection of collagenase clostridium histolyticum. Cases were reviewed for functional outcomes and operative difficulty. Seven metacarpophalangeal joints and 12 proximal interphalangeal joints in 11 patients were treated. Nine of the 11 patients were referred to the senior author after collagenase clostridium histolyticum injections by other hand surgeons; two patients had previous injections by the senior author. The average interval between most recent injection and salvage fasciectomy was 12 months. Intraoperative findings demonstrated disruption of normal architecture and areolar tissue, with extensive scar in the dissection planes after previous injection. Mean preoperative/postinjection joint contracture for metacarpophalangeal and proximal interphalangeal joints was 42 and 60 degrees, respectively; after surgery, joint contractures were 0 and 21 degrees, respectively. Significant improvement in postoperative range of motion was seen for both metacarpophalangeal and proximal interphalangeal joints after palmar fasciectomy. Collagenase clostridium histolyticum injections may produce a deeply scarred bed and increase the technical difficulty of salvage fasciectomy. However, results of palmar fasciectomy are comparable to those of primary fasciectomy even in the setting of recurrent or progressive disease. Therapeutic, IV.

  16. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

    PubMed Central

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-01-01

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients. PMID:18506179

  17. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

    PubMed

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-06-03

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

  18. [Salvage treatments following prostate radiation therapy: role of the urologist].

    PubMed

    Soulié, M; Salomon, L

    2014-10-01

    The management of recurrent prostate cancer after radiotherapy or brachytherapy is non-standardized and rapidly evolving. Local recurrence is observed on average in 30% of cases several years following irradiation. A key challenge is to determine the site of recurrence and imaging (MRI and PET choline) coupled to prostate biopsies are important to confirm the local character. Salvage therapy performed by the urologist can then control the situation. Radical prostatectomy subject to strict technical conditions is one of the most efficient local treatments, however it comes at the cost of significant urinary morbidity; minimally invasive therapies (focused ultrasound and cryotherapy) have also their place in specific indications. Each clinical situation should be discussed in pluridisciplinary meetings integrating the oncologic and functional status at recurrence, the risk/benefit ratio of each treatment, the patient's wishes and probability of survival.

  19. Peripheral blood monitoring of chronic myeloid leukemia during treatment with imatinib, second-line agents, and beyond.

    PubMed

    Lima, Lisa; Bernal-Mizrachi, Leon; Saxe, Debra; Mann, Karen P; Tighiouart, Mourad; Arellano, Martha; Heffner, Leonard; McLemore, Morgan; Langston, Amelia; Winton, Elliott; Khoury, Hanna Jean

    2011-03-15

    The current study was conducted to compare simultaneously obtained bone marrow (BM) cytogenetics (CTG), peripheral blood (PB) and BM fluorescence in situ hybridization (FISH), and quantitative real-time polymerase chain reaction (Q-PCR) for BCR-ABL1 in monitoring response to treatment with tyrosine kinase inhibitors and homoharringtonine (HHT) in patients with chronic myeloid leukemia (CML). PB and BM FISH (n = 112 samples) and/or Q-PCR (n = 132 samples) for BCR-ABL1 were simultaneously obtained in 70 patients with Philadelphia chromosome-positive (Ph+) CML in chronic (68%), accelerated (16%), and blast phase (16%) before the initiation of therapy and during the course of treatment with imatinib (IM) (n = 40 patients), dasatinib (n = 20 patients), nilotinib (n = 4 patients), bosutinib (n = 18 patients), or HHT (n = 4 patients) for patients with newly diagnosed (n = 13 patients), IM-sensitive (n = 34 patients), IM-resistant (n = 30 patients), or IM-intolerant (n = 9 patients) disease. Eighteen patients were found to have Ph+ variants or karyotypic abnormalities in addition to the Ph+. Excellent correlations (r) were observed between PB and BM FISH (r = 0.95) and PB and BM Q-PCR (r = 0.87), as well as BM CTG and PB FISH (r = 0.89) and PB Q-PCR (r = 0.82). This correlation was not affected by the presence of the Ph+ variant or additional chromosomal abnormalities, the presence of ABL1 kinase domain mutations, phase of the disease, or treatment. PB FISH and Q-PCR appear to be reliable methods with which to monitor response to modern therapy in patients with all phases of CML. Copyright © 2010 American Cancer Society.

  20. A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial.

    PubMed

    Mead, G M; Cullen, M H; Huddart, R; Harper, P; Rustin, G J S; Cook, P A; Stenning, S P; Mason, M

    2005-07-25

    This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m(-2) day 1, followed on days 1-5 by ifosfamide 1 g m(-2) intravenously (i.v.) and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR(-ve)); favourable response rate (FRR = CR + PR(-ve)) 60%, 95% CI (44-75%); survival at 1 year was 70% (56-84%) and failure-free survival 36% (22-50%). In the group of 26 patients meeting the 'good-risk' criteria described by the Memorial Hospital, the FRR was 73% (52-88%) compared with 41% (18-67%) for the 17 'poor-risk' patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.

  1. Cost-utility and budget impact analyses of gefitinib in second-line treatment for advanced non-small cell lung cancer from Thai payer perspective.

    PubMed

    Thongprasert, Sumitra; Tinmanee, Sirana; Permsuwan, Unchalee

    2012-03-01

    To evaluate the cost utility and budget impact of second-line gefitinib for non-small cell lung cancer from a Thai payer perspective.   A Markov model with three health states (pre-progression, post-progression and death) was constructed to estimate direct medical costs and outcomes comparing four treatment options, i.e., gefitinib, erlotinib, pemetrexed and docetaxel. The model followed patients for 2 years with discount rate of 3% annually. Clinical inputs and patients' characteristics were based on a randomized phase III trial (INTEREST). Costs were based on reference prices published by the Ministry of Public Health, Thailand, and other information related to treatment from expert opinion and presented in 2010. Deterministic and probabilistic sensitivity analyses were performed to determine the impact of model parameters on results. In the base case model, gefitinib and erlotinib yielded equal quality-adjusted life years (QALY) but 0.0140 and 0.0110 more QALY compared with docetaxel and pemetrexed, respectively. Total costs were 188 848 Baht (US$6237) for gefitinib, 196 313 Baht (US$6483) for docetaxel, 249 177 Baht (US$8229) for erlotinib and 275 303 Baht (US$9092) for pemetrexed. Drug acquisition contributed the greatest component. A series of sensitivity analyses demonstrated the robustness to various parameter variations except for docetaxel cost and duration of treatment. The budget impact analyses demonstrate the greater the percentage of substitution of gefitinib for docetaxel (ranging from 10-60%) the greater the cost saving.   Gefitinib is a dominant cost saving strategy compared with docetaxel for the second-line treatment of advanced NSCLC from the Thai payer perspective. © 2012 Blackwell Publishing Asia Pty Ltd.

  2. Second-line rescue triple therapy with levofloxacin after failure of non-bismuth quadruple "sequential" or "concomitant" treatment to eradicate H. pylori infection.

    PubMed

    Gisbert, Javier P; Molina-Infante, Javier; Marin, Alicia C; Vinagre, Gemma; Barrio, Jesus; McNicholl, Adrian Gerald

    2013-06-01

    Non-bismuth quadruple "sequential" and "concomitant" regimens, including a proton pump inhibitor (PPI), amoxicillin, clarithromycin and a nitroimidazole, are increasingly used as first-line treatments for Helicobacter pylori infection. Eradication with rescue regimens may be challenging after failure of key antibiotics such as clarithromycin and nitroimidazoles. To evaluate the efficacy and tolerability of a second-line levofloxacin-containing triple regimen (PPI-amoxicillin-levofloxacin) in the eradication of H. pylori after non-bismuth quadruple-containing treatment failure. prospective multicenter study. in whom a non-bismuth quadruple regimen, administered either sequentially (PPI + amoxicillin for 5 days followed by PPI + clarithromycin + metronidazole for 5 more days) or concomitantly (PPI + amoxicillin + clarithromycin + metronidazole for 10 days) had previously failed. levofloxacin (500 mg b.i.d.), amoxicillin (1 g b.i.d.) and PPI (standard dose b.i.d.) for 10 days. eradication was confirmed with (13)C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire. 100 consecutive patients were included (mean age 50 years, 62% females, 12% peptic ulcer and 88% dyspepsia): 37 after "sequential", and 63 after "concomitant" treatment failure. All patients took all medications correctly. Overall, per-protocol and intention-to-treat H. pylori eradication rates were 75.5% (95% CI 66-85%) and 74% (65-83%). Respective intention-to-treat cure rates for "sequential" and "concomitant" failure regimens were 74.4% and 71.4%, respectively. Adverse effects were reported in six (6%) patients; all of them were mild. Ten-day levofloxacin-containing triple therapy constitutes an encouraging second-line strategy in patients with previous non-bismuth quadruple "sequential" or "concomitant" treatment failure.

  3. Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment.

    PubMed

    Storr, Helen L; Plowman, P Nicholas; Carroll, Paul V; François, Inge; Krassas, Gerasimos E; Afshar, Farhad; Besser, G Michael; Grossman, Ashley B; Savage, Martin O

    2003-01-01

    Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.4-17.8 yr) with CD. All underwent TSS, and 11 were cured (postoperative serum cortisol, <50 nM). Seven (39%) had 0900-h serum cortisol of 269-900 nM during the immediate postoperative period (2-20 d), indicating lack of cure. These patients (6 males and 1 female; mean age, 12.8 yr; range, 6.4-17.8 yr; 4 prepubertal; 3 pubertal) received external beam RT to the pituitary gland, using a 6-MV linear accelerator, with a dose of 45 Gy in 25 fractions over 35 d. Until the RT became effective, hypercortisolemia was controlled with ketoconazole (dose, 200-600 mg/d) (n = 4) and metyrapone (750 mg-3 g/d) +/- aminoglutethimide (1 g/d) or o'p'DDD (mitotane, 3 mg/d) (n = 3). All patients were cured after pituitary RT. The mean interval from RT to cure (mean serum cortisol on 5-point day curve, <150 nM) was 0.94 yr (0.25-2.86 yr). Recovery of pituitary-adrenal function (mean cortisol, 150-300 nM) occurred at mean 1.16 yr (0.40-2.86 yr) post RT. At 2 yr post RT, puberty occurred early in one male patient (age, 9.8 yr) but was normal in the others. GH secretion was assessed at 0.6-2.5 yr post RT in all patients: six had GH deficiency (peak on glucagon/insulin provocation, <1.0-17.9 mU/liter) and received human GH replacement. Follow-up of pituitary function 7.6 and 9.5 yr post RT in two patients showed normal gonadotropin secretion and recovery of GH peak to 29.7 and 19.2 mU/liter. The seven patients were followed for mean 6.9 yr (1.4-12.0 yr), with no evidence of recurrence of CD. In conclusion, pituitary RT is an effective and relatively rapid-onset treatment for pediatric CD after failure of TSS. GH deficiency occurred in 86% patients. Long-term follow-up suggests some recovery of GH

  4. Moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection: effect of treatment duration and antibiotic resistance on the eradication rate.

    PubMed

    Yoon, Hyuk; Kim, Nayoung; Lee, Byoung Hwan; Hwang, Tae Jun; Lee, Dong Ho; Park, Young Soo; Nam, Ryoung Hee; Jung, Hyun Chae; Song, In Sung

    2009-10-01

    The aim of this study was to evaluate the efficacy of a moxifloxacin-containing triple therapy as second-line treatment for Helicobacter pylori infection. We also investigated the effect of treatment duration and antibiotic resistance on the eradication rate of this therapy. We prospectively enrolled patients found to have persistent H. pylori infections after failure of first-line proton-pump inhibitor-based triple therapy. Patients took moxifloxacin (400 mg q.d.), amoxicillin (1000 mg b.i.d.), and esomeprazole (20 mg b.i.d.). The eradication rate, drug compliance, and adverse event rates were evaluated. Minimal inhibitory tests were performed for moxifloxacin and amoxicillin by the agar dilution method. In 2004, 41 patients were treated for 7 days. The intention-to-treat and per-protocol eradication rates (ITT/PP) were 75.6/83.8%. Moxifloxacin resistance was 5.6%. Therapy was extended to 10 days during 2005-2006 and 139 patients were treated. The ITT/PP eradication rates were 71.9/82.6%; moxifloxacin resistance had increased to 12%. The final group of 181 patients in 2007-2008 who were treated for 14 days also had low eradication rates (68/79.9%), but there was no statistical significance in the efficacy among the treatment periods. Moxifloxacin resistance in 2007-2008 was 28.2%. Side-effect increased with treatment duration (i.e., 9.8, 12.2, and 25.4% at 7, 10, and 14 days, respectively, p = .001). The 7-day moxifloxacin-containing triple therapy produced an unacceptably low eradication rate. Increasing the duration of therapy was expected to increase the eradication rate, but the expected increased did not materialize, most likely because of coincident marked increase in the prevalence of resistance to moxifloxacin. Tailored treatment based on antibiotic susceptibility testing might be more effective in the achievement of high eradication rate when rapid antibiotic resistance such as moxifloxacin is occurring.

  5. Comparative efficacy and safety of second-line antiretroviral therapy for treatment of HIV/AIDS: a systematic review and network meta-analysis.

    PubMed

    Kanters, Steve; Socias, Maria Eugenia; Paton, Nicholas I; Vitoria, Marco; Doherty, Meg; Ayers, Dieter; Popoff, Evan; Chan, Keith; Cooper, David A; Wiens, Matthew O; Calmy, Alexandra; Ford, Nathan; Nsanzimana, Sabin; Mills, Edward J

    2017-10-01

    Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed. In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3-4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models. We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88-1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did

  6. Impact of second-line drug resistance on tuberculosis treatment outcomes in the United States: MDR-TB is bad enough.

    PubMed

    Althomsons, S P; Cegielski, J P

    2012-10-01

    The worldwide emergence of extensively drug-resistant tuberculosis (TB) has focused attention on treatment with second-line drugs (SLDs). To determine the impact on outcomes of resistance to individual SLDs, we analyzed successful treatment completion and death among drug-resistant TB cases in the US national TB surveillance system, 1993-2007 (N = 195 518). We defined four combinations of first-line drug (FLD) resistance based on isoniazid (INH) and rifamycin, and three patterns of SLD resistance: fluoroquinolones, injectable SLDs and other oral SLDs. We compared treatment outcomes of cases by FLD resistance, with and without each pattern of SLD resistance. In all but one instance, cases with FLD resistance but no SLD resistance had better outcomes than cases with SLD resistance. Rifamycin resistance, alone or with INH, resulted in a greater decline in treatment completion and greater increase in deaths than resistance to SLDs. Among patients with multidrug-resistant TB, additional resistance to injectable SLDs was statistically significant. Outcomes were better for human immunodeficiency virus (HIV) negative than HIV-positive cases for all resistance patterns, but improved among HIV-infected cases after 1998, when highly active antiretroviral treatment became widely available. These results suggest that the effect of rifamycin resistance may outweigh the more modest effects of resistance to specific SLDs.

  7. Letrozole as second-line hormonal treatment for recurrent low-grade endometrial stromal sarcoma: A case report and review of the literature

    PubMed Central

    Nakamura, Kohei; Nakayama, Kentaro; Ishikawa, Masako; Ishikawa, Noriyoshi; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Sato, Emi; Iida, Kohji; Sultana, Razia; Kyo, Satoru

    2016-01-01

    Low-grade endometrial stromal sarcoma (LGESS) is a rare malignancy. The tumor is reportedly responsive to hormonal therapy, most commonly with medroxyprogesterone acetate (MPA), but the effectiveness of aromatase inhibitors for recurrent LGESS remains unclear. The present study reports a case of stage IC LGESS presenting with abnormal uterine bleeding, and also provides a review of the literature. Following a total abdominal hysterectomy and bilateral salpingo-oophorectomy, MPA therapy was initiated; treatment was successful, but discontinued 19 months later due to disruptive side effects. A further 2 months later, the patient presented with recurrent disease and received chemotherapy. MPA treatment was restarted with a partial response. A second recurrence, 4 years later, presented with lung and para-aortic lymph node metastases. The patient responded to treatment with the aromatase inhibitor letrozole. The patient has since exhibited stable disease and remained free of symptoms for 7 years. This case suggests that aromatase-inhibitor treatment may be effective for recurrent LGESS as a second-line treatment. PMID:27895740

  8. Timing for starting second-line therapy in recurrent ovarian cancer.

    PubMed

    Guarneri, Valentina; Barbieri, Elena; Dieci, Maria Vittoria; Piacentini, Federico; Conte, PierFranco

    2011-01-01

    Ovarian cancer is the leading cause of gynecologic cancer-related death in Europe and the USA. The optimal treatment strategy for this malignancy includes accurate presurgical and surgical staging, optimal debulking surgery, and first-line therapy with platinum-based chemotherapy. Unfortunately, the majority of patients diagnosed with advanced ovarian cancer will eventually relapse and die. However, an appropriate management can have a major impact on survival: salvage chemotherapy can prolong survival in the majority of cases and, in selected patients, surgical cytoreduction of recurrent disease can be beneficial. The optimal timing for starting second-line therapy should be based on symptomatic or radiologic recurrence. In fact, even though cancer antigen 125 (CA 125) elevation significantly anticipates a clinical relapse, a randomized trial failed to show a survival advantage for starting second-line therapy on the basis of CA 125 elevation. This is the most solid evidence coming from a randomized trial; however, we must take into account some limitations: in this study the role of secondary cytoreduction was not considered and, at the time of study conduction, more active salvage drugs/regimens were not yet available. In the near future, a better knowledge of ovarian cancer biology, more sensitive diagnostic techniques, more accurate and less invasive surgical procedures along with the availability of new agents will further improve prognosis. In this scenario, the anticipation of salvage therapy will probably play a different role.

  9. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study

    PubMed Central

    Schultheis, B.; Folprecht, G.; Kuhlmann, J.; Ehrenberg, R.; Hacker, U. T.; Köhne, C. H.; Kornacker, M.; Boix, O.; Lettieri, J.; Krauss, J.; Fischer, R.; Hamann, S.; Strumberg, D.; Mross, K. B.

    2013-01-01

    Background Metastatic colorectal cancer (mCRC) is commonly treated with 5-fluorouracil, folinic acid, and oxaliplatin or irinotecan. The multitargeted kinase inhibitor, regorafenib, was combined with chemotherapy as first- or second-line treatment of mCRC to assess safety and pharmacokinetics (primary objectives) and tumor response (secondary objective). Patients and methods Forty-five patients were treated every 2 weeks with 5-fluorouracil 400 mg/m2 bolus then 2400 mg/m2 over 46 h, folinic acid 400 mg/m2, and either oxaliplatin 85 mg/m2 or irinotecan 180 mg/m2. On days 4–10, patients received regorafenib 160 mg orally once daily. Results The median duration of treatment was 108 (range 2–345 days). Treatment was stopped for adverse events or death (17 patients), disease progression (11 patients), and consent withdrawal or investigator decision (11 patients). Six patients remained on regorafenib at data cutoff (two without chemotherapy). Drug-related adverse events occurred in 44 patients [grade ≥3 in 32 patients: mostly neutropenia (17 patients) and leukopenia, hand–foot skin reaction, and hypophosphatemia (four patients each)]. Thirty-three patients achieved disease control (partial response or stable disease) for a median of 126 (range 42–281 days). Conclusion Regorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of irinotecan and SN-38 but no significant effect on 5-fluorouracil or oxaliplatin pharmacokinetics. PMID:23493136

  10. Risk adapted single-agent dactinomycin or carboplatin for second-line treatment of methotrexate resistant low-risk gestational trophoblastic neoplasia.

    PubMed

    Winter, M C; Tidy, J A; Hills, A; Ireson, J; Gillett, S; Singh, K; Hancock, B W; Coleman, R E

    2016-12-01

    To evaluate the outcome of patients treated with second-line chemotherapy for methotrexate-resistant low-risk GTN at the Sheffield Centre, UK between 2001 and 2015, including the novel use of single-agent carboplatin as a strategy to reduce exposure to combination chemotherapy. 392 low-risk GTN patients were treated with first-line methotrexate. The selection of chemotherapy regimen following methotrexate-resistance depended on the volume of residual disease as indicated by the serum hCG value at the time, with patients switching to either single-agent dactinomycin at an hCG level<150IU/L from 2001-2010 and <300IU/L since 2010, or to combination treatment with etoposide/dactinomycin (EA) above these thresholds. In order to reduce exposure to more toxic combination chemotherapy regimens, our treatment policy was revised in 2011, with the recommendation of single-agent carboplatin as an alternative to EA at hCG levels >300IU/L. 136 (35%) of 392 received second-line chemotherapy following methotrexate-resistance. 59 patients received single-agent dactinomycin with 53 (90%) patients achieving complete hCG response, 3 patients requiring combination chemotherapy or surgery, and 3 patients subsequently spontaneously resolving. 56 patients received EA chemotherapy with hCG complete response in 50 (89%) patients, and the remaining 6 patients were cured with further multi-agent chemotherapy or surgery. With carboplatin, 17/21 (81%) achieved an overall complete hCG response rate, with 4 patients requiring third-line EA. Carboplatin was well tolerated with no significant alopecia; myelosuppression was the most significant toxicity. Overall survival for all patients was 100%. These data show the continued excellent outcomes for methotrexate-resistant low-risk patients treated with single-agent dactinomycin or EA. Our experience with carboplatin is promising and provides an alternative regimen for methotrexate-resistant low-risk disease that avoids alopecia and in

  11. Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial.

    PubMed

    Hsu, Ping-I; Tsai, Feng-Woei; Kao, Sung-Shuo; Hsu, Wen-Hung; Cheng, Jin-Shiung; Peng, Nan-Jing; Tsai, Kuo-Wang; Hu, Huang-Ming; Wang, Yao-Kuang; Chuah, Seng-Kee; Chen, Angela; Wu, Deng-Chyang

    2017-09-01

    Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection. Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment. The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003). Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H

  12. Lower limb salvage surgery: modular endoprosthesis in bone tumour treatment.

    PubMed

    Orlic, D; Smerdelj, M; Kolundzic, R; Bergovec, M

    2006-12-01

    We retrospectively analysed 90 patients who underwent "en bloc" resection and modular endoprosthesis reconstruction in the lower limbs between 1987-2003. After proximal femur resection, reconstruction was performed with a modular endoprosthesis by Howmedica (KFTR, designed by Kotz) and modular revision endoprosthesis by W. Link or Lima-Lto (Revision system, designed by Wagner). The knee joint was reconstructed with a modular endoprosthesis (Howmedica, KFTR designed by Kotz) after distal femur or proximal tibia resection. Malignant bone tumours were present in 58 patients (64.5%), benign tumours in 16 (17.8%), metastases in 8 (8.9%), tumour-like lesions in 4 (4.4 %) and non-tumour-related destruction of the femur in 4 patients (4.4%). High-grade tumours were found in the majority of malignant bone tumours (70.7%). Treatment complications, which occurred in 26 patients, were: local recurrence of the tumour, deep infection, acetabular destruction following hemiarthroplasty, recurrent dislocations of endoprosthesis, periprosthetic fracture and hardware problems. In total, 23 patients (25.6%) died due to tumours. Endoprostheses should be considered as a treatment of choice for bone tumours in the hip and knee joint region. Advances in limb salvage surgery are, and will long continue to be, a great challenge for orthopaedic oncologists of the 21st century.

  13. Survival without common toxicity criteria grade 3/4 toxicity following second-line treatment with pemetrexed for nonsquamous non-small cell lung cancer in Chinese patients.

    PubMed

    Wu, Yi-Long; Sun, Yan; Zhou, Cai-Cun; Zhang, Li; Yu, Shi-Ying; Ma, Sheng-Lin; Han, Ling Lucia; Zhang, Xiao-Qing Rosetta; Orlando, Mauro

    2013-01-01

    The efficacy of pemetrexed in the second-line treatment of Chinese patients with advanced non-small cell lung cancer (NSCLC) has been shown to be similar to that of docetaxel in a recent study; additionally, pemetrexed was associated with much better safety and toxicity profiles. Here, the survival without common toxicity criteria grade 3/4 toxicity (SWT) data from a post hoc analysis of this recent prospective NSCLC study in Chinese patients is reported. This post hoc analysis differs from the main study; it focuses on the nonsquamous population to align with the current approval for pemetrexed in China. A total of 154 patients with nonsquamous NSCLC received either pemetrexed (500 mg/m(2) intravenously (IV)) or docetaxel (75 mg/m(2) IV) on day 1 of 21-day cycles. SWT was analyzed using Kaplan-Meier and univariate Cox methods. Patients treated with pemetrexed had a longer median SWT than patients treated with docetaxel (7.4 months versus 1.2 months; unadjusted hazard ratio = 0.59, 95% confidence interval (CI): 0.41-0.84; P = 0.003). At 12 and 18 months, the SWT event-free probability for pemetrexed patients (18 months: 24.5%, 95%CI 13.9%-36.6%, vs. 12.3%, 95% CI 4.8%-23.6%) was greater than that for docexatel patients (12 months: 37.3%, 95% CI 26.5%-48.0%, vs. 23.3%, 95% CI 14.4-33.4). The progression-free survival without common toxicity criteria grade 3/4 toxicity (PFS-WT) was also statistically significantly longer for patients treated with pemetrexed than patients treated with docetaxel (1.9 months vs. 1.1 months, P = 0.002). Chinese patients with nonsquamous NSCLC disease treated with pemetrexed had improved SWT beyond 6 months than those receiving docetaxel. This analysis supports a benefit-to-risk profile that favors pemetrexed over docetaxel in the second-line treatment of Chinese nonsquamous NSCLC patients.

  14. Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997–2010

    PubMed Central

    Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; DiMeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

    2014-01-01

    Background Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Methods Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004–2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997–2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Results Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). Conclusions We found a significant increase in overall survival, PFS, and survival after

  15. Real-life comparison of severe vascular events and other non-hematological complications in patients with chronic myeloid leukemia undergoing second-line nilotinib or dasatinib treatment.

    PubMed

    Gora-Tybor, Joanna; Medras, Ewa; Calbecka, Malgorzata; Kolkowska-Leśniak, Agnieszka; Ponikowska-Szyba, Edyta; Robak, Tadeusz; Jamroziak, Krzysztof

    2015-01-01

    We retrospectively analyzed the rates of significant non-hematological adverse events (AEs) in 105 patients with chronic myeloid leukemia (CML) treated with second-generation tyrosine kinase inhibitor (TKIs) dasatinib or nilotinib used as second-line therapy in Polish tertiary care centers. Our analysis revealed that in a "real life setting," nearly half of patients with CML on second-generation TKIs suffer from therapy complications. Grade 2-5 non-hematological AEs were observed in 40% of patients treated with nilotinib and in 42% treated with dasatinib (p=0.83). Severe vascular events including peripheral artery occlusive disease (PAOD) occurred in 11% of patients on nilotinib and 4% on dasatinib (p=0.16). Pleural effusion occurred more often in the dasatinib group (26%) than in the nilotinib group (2%) (p=0.003). Importantly, most AEs occurred late, after more than 1 year of treatment. Since AEs are most often the reason for poor therapy compliance, careful monitoring of tolerability is crucial for an optimal treatment response in CML.

  16. Important differences in the durability of glycaemic response among second-line treatment options when added to metformin in type 2 diabetes: a retrospective cohort study.

    PubMed

    Mamza, Jil; Mehta, Rajnikant; Donnelly, Richard; Idris, Iskandar

    2016-01-01

    There is limited information about the durability of glycaemic control when different oral glucose-lowering therapies (GLTs) are used as add-on treatments to metformin (MET) in patients with type 2 diabetes mellitus (T2DM). To compare time to treatment failure between different classes of oral GLT when used as second line (add-on) treatments to MET monotherapy at HbA1c ≥ 7.5%. A retrospective cohort study on 20,070 patients who were newly treated with a sulphonylurea (SU), dipeptidyl-peptidase-4 (DPP-4) inhibitor or thiazolidinedione (TZD) following MET therapy failure (2007-2014). Patients' data was sourced from UK General Practices via The Health Improvement Network (THIN) database. The risk of dual therapy failure was compared between three treatment groups: MET + SU (reference group, n = 15,508), MET + DPP-4 inhibitor (n = 3,080) and MET + TZD (n = 1,482). Follow-up was until treatment substitution or intensification with a 3rd GLT, or for up to 5 years (totalling 46,430 person-years). Propensity score weighting and Cox proportional hazard regression analyses were employed. Risk of dual therapy failure was compared between treatment groups while adjusting for baseline covariates. Unadjusted survival analysis showed the incidence of dual therapy failure at 1 year was 15% with SU, 23% with DPP-4 inhibitor and 8% with TZD. Corresponding failure rates at 2 years were 26, 38 and 12%, respectively. Adjusted multivariate models showed that, compared to the SU group, adding a DPP-4 inhibitor was associated with an increased risk of treatment failure (adjusted hazard ratio, aHR, 1.58; 95% CI: 1.48-1.68), while adding a TZD was associated with a reduced hazard (aHR, 0.45; 95% CI: 0.41-0.50). Baseline parameters associated with an increased hazard of intensification included HbA1c, diabetes duration, gender, smoking status and the use of statins. In routine clinical practice, adding a DPP-4 inhibitor to MET is associated with an increased

  17. Everolimus for the second-line treatment of advanced and/or metastatic renal cell cancer: a critique of the submission from Novartis.

    PubMed

    Pitt, M; Crathorne, L; Moxham, T; Bond, M; Hyde, C

    2010-10-01

    This paper represents a summary of the evidence review group (ERG) report into the clinical efficacy, safety and cost-effectiveness of everolimus plus best supportive care (BSC) for the treatment of advanced renal cell carcinoma (RCC) which has progressed following or on vascular endothelial growth factor-targeted therapy (sunitinib, sorafenib, bevacizumab), compared to BSC alone. The submitting manufacturer's case for clinical effectiveness and cost-effectiveness was mainly based on a well-conducted randomised controlled trial (RCT), Renal Cell Cancer Treatment with Oral RAD001 Given Daily-1 (RECORD-1), comparing BSC plus everolimus with BSC plus placebo and a de novo economic model. The RCT indicated a marked statistically significant effect on progression-free survival. The base-case incremental cost-effectiveness ratio (ICER) estimate was 52,000 pounds per quality-adjusted life-year (this included a reduction in drug cost associated with an approved patient access scheme). The ERG undertook a critical appraisal of the submission. The ERG was generally in agreement with the submitting manufacturer concerning its estimates of effectiveness; however, there was greater concern surrounding the estimates of cost-effectiveness. The ERG judged that if potential errors in the model were corrected, the ICERs offered by the submitting manufacturer would overstate the cost-effectiveness of everolimus for the second-line treatment of metastatic RCC (that this ICER would be a higher value). Concerning the estimates of cost-effectiveness in RCC, the observations in the ERG report provide strong further support for research collecting rigorous estimates of utilities associated with the main health states likely to be experienced by patients with renal cell cancer. At the time of writing, NICE was yet to issue the Appraisal Consultation Document for this appraisal.

  18. Ramucirumab as Second-Line Treatment in Patients With Advanced Hepatocellular Carcinoma: Analysis of REACH Trial Results by Child-Pugh Score.

    PubMed

    Zhu, Andrew X; Baron, Ari David; Malfertheiner, Peter; Kudo, Masatoshi; Kawazoe, Seiji; Pezet, Denis; Weissinger, Florian; Brandi, Giovanni; Barone, Carlo A; Okusaka, Takuji; Wada, Yoshiyuki; Park, Joon Oh; Ryoo, Baek-Yeol; Cho, Jae Yong; Chung, Hyun Cheol; Li, Chung-Pin; Yen, Chia-Jui; Lee, Kuan-Der; Chang, Shao-Chun; Yang, Ling; Abada, Paolo B; Chau, Ian

    2016-09-22

    REACH is the first phase 3 trial to provide information on hepatocellular cancer (HCC) in the second-line (postsorafenib) setting categorized by Child-Pugh score, a scoring system used to measure the severity of chronic liver disease. This exploratory analysis demonstrates the relationship between a potential ramucirumab survival benefit, severity of liver disease, and baseline α-fetoprotein (αFP). To assess treatment effects and tolerability of ramucirumab by Child-Pugh score in patients with HCC enrolled in the REACH trial. Randomized, double-blind, phase 3 trial of ramucirumab and best supportive care vs placebo and best supportive care as second-line treatment in patients with HCC enrolled between November 4, 2010 and April 18, 2013, from 154 global sites. Overall, 643 patients were randomized and included in this analysis; 565 patients considered Child-Pugh class A (Child-Pugh scores 5 and 6) and 78 patients considered class B (Child-Pugh scores 7 and 8). Ramucirumab (8 mg/kg) or placebo intravenously plus best supportive care every 2 weeks. Overall survival (OS), defined as time from randomization to death from any cause. In the randomized population of 643 patients (mean [SD] age, 62.8 [11.1] years) in this analysis, a potential ramucirumab OS benefit was observed for patients with a Child-Pugh score of 5 (hazard ratio [HR], 0.80; 95% CI, 0.63-1.02; P = .06) but no apparent benefit for patients with Child-Pugh scores of 6 or 7 and 8. In patients with baseline αFP levels of 400 ng/mL (to convert ng/mL to μg/L, multiply by 1.0) or more, a ramucirumab OS benefit was significant for a score of Child-Pugh 5 (HR, 0.61; 95% CI, 0.43-0.87; P = .01) and Child-Pugh 6 (HR, 0.64; 95% CI, 0.42-0.98; P = .04), but was not significant for Child-Pugh 7 and 8. The overall safety profile of ramucirumab, regardless of Child-Pugh score, was considered manageable. Regardless of treatment arm, patients with Child-Pugh scores of 7 and 8 experienced a higher

  19. Treatment Outcomes of Patients With Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis According to Drug Susceptibility Testing to First- and Second-line Drugs: An Individual Patient Data Meta-analysis

    PubMed Central

    Bastos, Mayara L.; Hussain, Hamidah; Weyer, Karin; Garcia-Garcia, Lourdes; Leimane, Vaira; Leung, Chi Chiu; Narita, Masahiro; Penã, Jose M.; Ponce-de-Leon, Alfredo; Seung, Kwonjune J.; Shean, Karen; Sifuentes-Osornio, José; Van der Walt, Martie; Van der Werf, Tjip S.; Yew, Wing Wai; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E.D.; Chiang, C.Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W.C.M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K.; Flood, J.; Gandhi, N.; Garcia-Garcia, L.; Granich, R.M.; Hollm-Delgado, M.G.; Holtz, T.H.; Hopewell, P.; Iseman, M.; Jarlsberg, L.G.; Keshavjee, S.; Kim, H.R.; Koh, W.J.; Lancaster, J.; Lange, C.; Leimane, V.; Leung, C.C.; Li, J.; Menzies, D.; Migliori, G.B.; Mitnick, C.M.; Narita, M.; Nathanson, E.; Odendaal, R.; O'Riordan, P.; Pai, M.; Palmero, D.; Park, S.K.; Pasvol, G.; Pena, J.; Pérez-Guzmán, C.; Ponce-de-Leon, A.; Quelapio, M.I.D.; Quy, H.T.; Riekstina, V.; Robert, J.; Royce, S.; Salim, M.; Schaaf, H.S.; Seung, K.J.; Shah, L.; Shean, K.; Shim, T.S.; Shin, S.S.; Shiraishi, Y.; Sifuentes-Osornio, J.; Sotgiu, G.; Strand, M.J.; Sung, S.W.; Tabarsi, P.; Tupasi, T.E.; Vargas, M.H.; van Altena, R.; van der Walt, M.; van der Werf, T.S.; Viiklepp, P.; Westenhouse, J.; Yew, W.W.; Yim, J.J.

    2014-01-01

    Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis. PMID:25097082

  20. Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

    PubMed Central

    Isaakidis, Petros; Varghese, Bhanumati; Mansoor, Homa; Cox, Helen S.; Ladomirska, Joanna; Saranchuk, Peter; Da Silva, Esdras; Khan, Samsuddin; Paryani, Roma; Udwadia, Zarir; Migliori, Giovanni Battista; Sotgiu, Giovanni; Reid, Tony

    2012-01-01

    in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment. PMID:22792406

  1. Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT.

    PubMed

    Murata, M; Ikegame, K; Morishita, Y; Ogawa, H; Kaida, K; Nakamae, H; Ikeda, T; Nishida, T; Inoue, M; Eto, T; Kubo, K; Sakura, T; Mori, T; Uchida, N; Ashida, T; Matsuhashi, Y; Miyazaki, Y; Ichinohe, T; Atsuta, Y; Teshima, T

    2017-02-01

    A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5-18.5 mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (<2.0, 2.0-3.9 and ⩾4.0 mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (⩾50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34-4.85; P=0.004 for 2.0-3.9 mg/kg group and 1.79; 0.91-3.55; P=0.093 for ⩾4.0 mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and <2.0 mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.

  2. Low-dose weekly paclitaxel as second-line treatment for advanced non-small cell lung cancer: a phase II study.

    PubMed

    Juan, Oscar; Albert, Ana; Ordoño, Fermín; Casany, Rosa; Carañana, Vicente; Campos, Juan M; Alberola, Vicente

    2002-11-01

    To assess the activity and toxicity of low-dose weekly paclitaxel in patients with non-resectable or metastatic non-small cell lung cancer (NSCLC) and who had disease recurrence or failure with previous chemotherapy. Forty patients with NSCLC previously treated with platinum-based chemotherapy received weekly paclitaxel 80 mg/m(2) as a 1 h infusion. The median age was 63 years (range 42-77 years); 25 patients had Eastern Cooperative Oncology Group performance status (PS) 1 and 15 had PS 2. Thirty-one patients had stage IV disease and nine stage III (eight stage IIIB and one stage IIIA). A total of 364 weeks of treatment were administered (median 8 weeks, range 2-17 weeks). There were no episodes of grade 3 or 4 haematological toxicities. Severe non-haematological toxicity was uncommon: grade 1-2 asthenia in 50%; grade 1-2 motor neuropathy in 45% and grade 3 in 10%; grade 1-2 sensory neuropathy in 62% of patients. Alopecia was mild. The overall response rate was 37.5% (95% CI, 23.9-55): 2 CR, 13 PR, 15 SD, 8 PD, 2 NE. Median overall survival was 9.7 months (95% CI, 6.5-12.8). Median time to progression was 5.4 months (95% CI, 1.8-8.9). A low-dose weekly paclitaxel regimen had good clinical efficacy with low toxicity in this group of patients with poor prognosis. This regimen increases the therapeutic options available for second-line therapy in NSCLC patients.

  3. Analysis of KRAS/NRAS Mutations in a Phase III Study of Panitumumab with FOLFIRI Compared with FOLFIRI Alone as Second-line Treatment for Metastatic Colorectal Cancer.

    PubMed

    Peeters, Marc; Oliner, Kelly S; Price, Timothy J; Cervantes, Andrés; Sobrero, Alberto F; Ducreux, Michel; Hotko, Yevhen; André, Thierry; Chan, Emily; Lordick, Florian; Punt, Cornelis J A; Strickland, Andrew H; Wilson, Gregory; Ciuleanu, Tudor E; Roman, Laslo; Van Cutsem, Eric; He, Pei; Yu, Hua; Koukakis, Reija; Terwey, Jan-Henrik; Jung, Andre S; Sidhu, Roger; Patterson, Scott D

    2015-12-15

    We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective-retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) were coprimary endpoints. The RAS ascertainment rate was 85%; 18% of wild-type KRAS exon 2 tumors harbored other RAS mutations. For PFS and OS, the hazard ratio (HR) for panitumumab plus FOLFIRI versus FOLFIRI alone more strongly favored panitumumab in the wild-type RAS population than in the wild-type KRAS exon 2 population [PFS HR, 0.70 (95% confidence interval [CI], 0.54-0.91); P = 0.007 vs. 0.73 (95% CI, 0.59-0.90); P = 0.004; OS HR, 0.81 (95% CI, 0.63-1.03); P = 0.08 vs. 0.85 (95% CI, 0.70-1.04); P = 0.12]. Patients with RAS mutations were unlikely to benefit from panitumumab. Among RAS wild-type patients, the objective response rate was 41% in the panitumumab-FOLFIRI group versus 10% in the FOLFIRI group. Patients with RAS mutations were unlikely to benefit from panitumumab-FOLFIRI and the benefit-risk of panitumumab-FOLFIRI was improved in the wild-type RAS population compared with the wild-type KRAS exon 2 population. These findings support RAS testing for patients with mCRC. Clin Cancer Res; 21(24); 5469-79. ©2015 AACR.See related commentary by Salazar and Ciardiello, p. 5415. ©2015 American Association for Cancer Research.

  4. Salvage Treatment Improved Survival of Patients With Relapsed Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type

    SciTech Connect

    Zhang Xinxing; Xie Conghua; Xu Yong; Deng Di; Zhao Yanhai; Zou Bingwen; Zhou Lin; Li Mei; Wang Jin; Liu Weiping; Huang Meijuan

    2009-07-01

    Purpose: To evaluate the clinical outcome of salvage treatment for patients with relapsed natural killer (NK)/T-cell lymphoma, nasal type. Methods and Materials: Forty-four patients who had achieved complete response during initial treatment and experienced histologically proven relapse were reviewed. Twenty-nine of them received salvage treatment with radiotherapy (RT) alone (n = 7), chemotherapy (CT) alone (n = 10), or both RT and CT (n = 12); the other 15 patients received best supportive care alone. Results: The estimated 5-year overall survival (OS) rate for patients with or without salvage treatment was 37.8% vs. 0 (p < 0.0001), respectively. Salvage CT did not improve survival of relapsed Stage IE and IIE patients. Among relapsed Stage IIIE and IVE patients who received salvage treatment, RT developed significantly better survival when compared with that of non-RT (1-year OS, 62.5% vs. 0, p = 0.006). Relapsed Ann Arbor stage and receiving salvage treatment were found to be significant factors influencing OS at both univariate and multivariate levels. Conclusions: Salvage treatment improved survival in patients with relapsed NK/T-cell lymphoma, nasal type. Salvage RT may play an important role in salvage treatment of relapsed extranodal NK/T-cell lymphoma.

  5. Topotecan, pegylated liposomal doxorubicin hydrochloride and paclitaxel for second-line or subsequent treatment of advanced ovarian cancer: a systematic review and economic evaluation.

    PubMed

    Main, C; Bojke, L; Griffin, S; Norman, G; Barbieri, M; Mather, L; Stark, D; Palmer, S; Riemsma, R

    2006-03-01

    To examine the clinical effectiveness and cost-effectiveness of intravenous formulations of topotecan monotherapy, pegylated liposomal doxorubicin hydorocholoride (PLDH) monotherapy and paclitaxel used alone or in combination with a platinum-based compound for the second-line or subsequent treatment of advanced ovarian cancer. Electronic databases covering publication years 2000-4. Company submissions. Seventeen databases were searched for randomised controlled trials (RCTs) and systematic reviews for the clinical effectiveness of PLDH, topotecan and paclitaxel and economic evaluations of the cost-effectiveness of PLDH, topotecan and paclitaxel. Selected studies were quality assessed and data extracted, as were the three company submissions. A new model was developed to assess the costs of the alternative treatments, the differential mean survival duration and the impact of health-related quality of life. Monte-Carlo simulation was used to reflect uncertainty in the cost-effectiveness results. Nine RCTs were identified. In five of these trials, both the comparators were used within their licensed indications. Of these five, three included participants with both platinum-resistant and platinum-sensitive advanced ovarian cancer, and a further two only included participants with platinum-sensitive disease. The comparators that were assessed in the three trials that included both subtypes of participants were PLDH versus topotecan, topotecan versus paclitaxel and PLDH versus paclitaxel. In the further two trials that included participants with the subtype of platinum-sensitive disease, the comparators that were assessed were single-agent paclitaxel versus a combination of cyclophosphamide, doxorubicin and cisplatin (CAP) and paclitaxel plus platinum-based chemotherapy versus conventional platinum-based therapy alone. A further four trials were identified and included in the review in which one of the comparators in the trial was used outside its licensed indication

  6. Second line of defense program

    SciTech Connect

    Cantut, L; Thomas, L L

    1999-07-15

    Since the collapse of the Soviet Union, the prospect of nuclear materials entering the world market has become an ever-increasing threat. The Second Line of Defense (SLD) program was developed by the U.S. Department of Energy's (DOE) Nuclear Transfer and Supplier Policy Division (NN-43) to assist the Russian Federation State Customs Committee (RFSCC) in strengthening its capability to prevent illicit trafficking of nuclear materials across Russia's borders. The SLD program is a natural complement to the Material Protection Control and Accounting (MPC and A) program, which represents a first line of defense against the theft and diversion of nuclear materials. The SLD program is the first U.S.-Russian cooperative program to combat the illicit trafficking of nuclear and nuclear-related materials to would-be proliferators across Russia's borders.

  7. Second-line treatment of stage III/IV non-small-cell lung cancer (NSCLC) with pemetrexed in routine clinical practice: evaluation of performance status and health-related quality of life.

    PubMed

    Schuette, Wolfgang; Tesch, Hans; Büttner, Hartwig; Krause, Thomas; Soldatenkova, Victoria; Stoffregen, Clemens

    2012-01-13

    Second-line treatment of advanced non-small-cell lung cancer (NSCLC) improves overall survival. There is a lack of data regarding the impact on patients' overall health condition. This prospective, non-interventional study evaluated performance status (PS) and health-related quality of life (HR-QoL) during second-line pemetrexed treatment in routine clinical practice. Stage III/IV NSCLC patients who initiated second-line pemetrexed (standard vitamin and dexamethasone supplementation) were observed for a maximum of 9 treatment cycles. The primary objective was to evaluate the proportion of patients achieving improvement of Karnofsky Index (KI) of ≥ 10% (absolute) or maintaining KI ≥ 80% after the second treatment cycle ("KI benefit response"). HR-QoL was self-rated using the EuroQoL-5D questionnaire (EQ-5D). Factors potentially associated with KI benefit response were evaluated using logistic regression models. Of 521 eligible patients (73.5% Stage IV, median age 66.3 yrs, 36.1% ≥ 70 yrs, 62.0% with KI ≥ 80%), 471 (90.4%) completed at least 2 treatment cycles. 58.0% (95%CI 53.6%;62.2%) achieved KI benefit response after the second cycle. Patients with baseline KI ≥ 80%, no Grade 3/4 toxicities during the first 2 cycles, or combination regimen as prior first-line therapy were more likely to achieve a KI benefit response. EQ-5D scores improved over time. Grade 3/4 toxicities were reported in 23.8% of patients (mainly fatigue/asthenia 15.9%, neutropenia 8.7%). In this large prospective, non-interventional study of second-line pemetrexed treatment in patients with advanced NSCLC, including 36% elderly patients ( ≥ 70 years), physician-rated PS and self-rated HR-QoL were maintained or improved in the majority of patients. Registered on ClinicalTrials.gov (NCT00540241) on October 4, 2007.

  8. Salvage therapy for multidrug-resistant tuberculosis.

    PubMed

    Seung, K J; Becerra, M C; Atwood, S S; Alcántara, F; Bonilla, C A; Mitnick, C D

    2014-05-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis resistant to both isoniazid and rifampicin, is challenging under the best of circumstances, and particularly in resource-limited settings. For patients who remain persistently sputum-culture-positive despite therapy with second-line TB drugs, treatment options are limited, especially if disease is too advanced for resective surgery. Salvage therapy refers to the design of a regimen combining new and previously used drugs in a final effort to attain sputum conversion before declaring treatment to have failed. We retrospectively evaluated the outcomes of salvage therapy in 213 Peruvian patients. Salvage regimens included a median of two new drugs (range 1-6) and nine (range 5-13) total (new plus previously used) drugs. The most frequently used new drug was moxifloxacin, followed by capreomycin, amoxicillin-clavulanate, kanamycin and clarithromycin. Culture conversion occurred in 65 (30.5%) patients. Salvage regimens that included moxifloxacin were significantly more likely to be followed by culture conversion (OR 2.2; p 0.02). Later-generation fluoroquinolones such as moxifloxacin should be used in salvage therapy but also in the initial treatment of MDR-TB, if the best clinical strategy is to use the most effective drugs when the patient has the best chance for cure. New TB drugs are most likely to be initially used in salvage patients, in conditions similar to those described here. Close bacteriological monitoring of these patients will be essential, as useful information about the best way to use these new drugs can be gained from analysis of salvage therapy cohorts.

  9. Increased prevalence of poor sulphoxidation in patients with rheumatoid arthritis: effect of changes in the acute phase response and second line drug treatment.

    PubMed Central

    Emery, P; Bradley, H; Gough, A; Arthur, V; Jubb, R; Waring, R

    1992-01-01

    A minority of normal subjects have an impaired ability to oxidise sulphur, which is associated with an increased risk of side effects when they receive sulphur containing drugs. In 114 patients with rheumatoid arthritis a greatly increased prevalence of poor sulphoxidation was found in 82 (72%) patients compared with 70/200 (35%) healthy controls, 45/121 (37%) controls matched for age, and 4/35 (11%) of the normal aged general population. In a longitudinal study of 37 patients there was no significant alteration in sulphoxidation status after the introduction of a second line drug or with marked changes in the acute phase response. It seems, therefore, that the poor sulphoxidation status in patients with RA is not an epiphenomenon and may be an important factor in determining the clinical features of rheumatoid disease. PMID:1575574

  10. Intratympanic steroids as a salvage treatment for sudden sensorineural hearing loss? A meta-analysis.

    PubMed

    Ng, Jia Hui; Ho, Roger Chun Man; Cheong, Crystal Shuk Jin; Ng, Adele; Yuen, Heng Wai; Ngo, Raymond Yeow Seng

    2015-10-01

    Sudden sensorineural hearing loss is typically treated with systemic steroids. The aim of this meta-analysis was to evaluate the efficacy of salvage intratympanic steroid treatment in patients who have initial treatment failure with systemic steroids. A MEDLINE literature search was performed, supported by searches of Web of Science, Biosis, and Science Direct. Articles of all languages were included. Selection of relevant publications was conducted independently by three authors. Only randomized controlled trials were considered. In one arm of the studies, the patients received salvage intratympanic steroids. In the other arm, patients did not receive further treatment. The standard difference in mean (SDM) amount of improvement in hearing threshold between patients who did and did not receive salvage intratympanic steroids was calculated. From an initial 184 studies found via the search strategy, 5 studies met inclusion criteria and were included. There was a statistically significant greater reduction in hearing threshold on pure-tone audiometry in patients who received salvage intratympanic steroids than in those who did not (SDM = -0.401, p = 0.005). Subgroup analysis showed that administration by intratympanic injection (SDM = -0.375, p = 0.013) rather than a round window catheter (SDM = -0.629, p = 0.160) yielded significant improvement in outcome. The usage of dexamethasone yielded better outcomes (SDM = -0.379, p = 0.039) than the use of methylprednisolone (SDM = -0.459, p = 0.187). No serious side effect of treatment was reported. In patients who have failed initial treatment with systemic steroids, additional treatment with salvage intratympanic dexamethasone injections demonstrate a statistically significant reduction in the hearing thresholds as compared to controls.

  11. Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease

    PubMed Central

    Ngoma, T; Adde, M; Durosinmi, M; Githang’a, J; Aken’Ova, Y; Kaijage, J; Adeodou, O; Rajab, J; Brown, BJ; Leoncini, L; Naresh, K; Raphael, M; Hurwitz, N; Scanlan, P; Rohatiner, A; Venzon, D; Magrath, I

    2012-01-01

    Prior to the introduction of the International Network for Cancer Treatment and Research (INCTR) protocol INCTR 03-06, survival of patients with Burkitt lymphoma at 4 tertiary care centres in equatorial Africa was probably no more than 10–20%. The results reported here for 356 patients have demonstrated marked improvement in survival through the use of a uniform treatment protocol consisting of cyclophosphamide, methotrexate, vincristine, and intrathecal therapy, and the introduction of non-cross resistant second-line (salvage) therapy, consisting of ifosfamide, mesna, etoposide and cytarabine, when patients failed to achieve a complete response to first-line therapy or relapsed early. Overall survival rates of 67% and 62% were observed at 1 and 2 years (relapse is rare after one year). Of interest was the small impact of cerebrospinal fluid (CSF) and bone marrow involvement on outcome. However, the presence or absence of abdominal involvement clearly defined two prognostic groups. An additional finding was the association between CSF pleocytosis and orbital tumours, suggesting that spread of tumour cells to the central nervous system may occur via direct involvement of cranial nerves in the orbit. Survival rates may be increased in patients with abdominal involvement by combining first- and second-line therapy, but verification will require a further clinical study. PMID:22844968

  12. High rate of virological failure and low rate of switching to second-line treatment among adolescents and adults living with HIV on first-line ART in Myanmar, 2005-2015

    PubMed Central

    Harries, Anthony D.; Kumar, Ajay M. V.; Oo, Myo Minn; Kyaw, Khine Wut Yee; Win, Than; Aung, Thet Ko; Min, Aung Chan; Oo, Htun Nyunt

    2017-01-01

    Background The number of people living with HIV on antiretroviral treatment (ART) in Myanmar has been increasing rapidly in recent years. This study aimed to estimate rates of virological failure on first-line ART and switching to second-line ART due to treatment failure at the Integrated HIV Care program (IHC). Methods Routinely collected data of all adolescent and adult patients living with HIV who were initiated on first-line ART at IHC between 2005 and 2015 were retrospectively analyzed. The cumulative hazard of virological failure on first-line ART and switching to second-line ART were estimated. Crude and adjusted hazard ratios were calculated using the Cox regression model to identify risk factors associated with the two outcomes. Results Of 23,248 adults and adolescents, 7,888 (34%) were tested for HIV viral load. The incidence rate of virological failure among those tested was 3.2 per 100 person-years follow-up and the rate of switching to second-line ART among all patients was 1.4 per 100 person-years follow-up. Factors associated with virological failure included: being adolescent; being lost to follow-up at least once; having WHO stage 3 and 4 at ART initiation; and having taken first-line ART elsewhere before coming to IHC. Of the 1032 patients who met virological failure criteria, 762 (74%) switched to second-line ART. Conclusions We found high rates of virological failure among one third of patients in the cohort who were tested for viral load. Of those failing virologically on first-line ART, about one quarter were not switched to second-line ART. Routine viral load monitoring, especially for those identified as having a higher risk of treatment failure, should be considered in this setting to detect all patients failing on first-line ART. Strategies also need to be put in place to prevent treatment failure and to treat more of those patients who are actually failing. PMID:28182786

  13. High rate of virological failure and low rate of switching to second-line treatment among adolescents and adults living with HIV on first-line ART in Myanmar, 2005-2015.

    PubMed

    Kyaw, Nang Thu Thu; Harries, Anthony D; Kumar, Ajay M V; Oo, Myo Minn; Kyaw, Khine Wut Yee; Win, Than; Aung, Thet Ko; Min, Aung Chan; Oo, Htun Nyunt

    2017-01-01

    The number of people living with HIV on antiretroviral treatment (ART) in Myanmar has been increasing rapidly in recent years. This study aimed to estimate rates of virological failure on first-line ART and switching to second-line ART due to treatment failure at the Integrated HIV Care program (IHC). Routinely collected data of all adolescent and adult patients living with HIV who were initiated on first-line ART at IHC between 2005 and 2015 were retrospectively analyzed. The cumulative hazard of virological failure on first-line ART and switching to second-line ART were estimated. Crude and adjusted hazard ratios were calculated using the Cox regression model to identify risk factors associated with the two outcomes. Of 23,248 adults and adolescents, 7,888 (34%) were tested for HIV viral load. The incidence rate of virological failure among those tested was 3.2 per 100 person-years follow-up and the rate of switching to second-line ART among all patients was 1.4 per 100 person-years follow-up. Factors associated with virological failure included: being adolescent; being lost to follow-up at least once; having WHO stage 3 and 4 at ART initiation; and having taken first-line ART elsewhere before coming to IHC. Of the 1032 patients who met virological failure criteria, 762 (74%) switched to second-line ART. We found high rates of virological failure among one third of patients in the cohort who were tested for viral load. Of those failing virologically on first-line ART, about one quarter were not switched to second-line ART. Routine viral load monitoring, especially for those identified as having a higher risk of treatment failure, should be considered in this setting to detect all patients failing on first-line ART. Strategies also need to be put in place to prevent treatment failure and to treat more of those patients who are actually failing.

  14. [Effect of treatment and HIV drug resistance of 81 cases of HCV/HIV co-infected individuals who had received AIDS second-line antiretroviral treatment in Henan province].

    PubMed

    Sun, Dingyong; Liu, Jia; Wang, Qi; Yang, Wenjie; Yue, Yanchao; Guo, Zhiyong; Yang, Shimei; Zhu, Qian; Wang, Zhe

    2015-06-01

    To understand the one-year effect of HCV/HIV co-infected patients who had received AIDS second-line antiretroviral treatment after failure virologically, on the first-line therapy. HCV and HIV antibody positive patients who had experienced virological failure but received at least one-year AIDS first-line treatment, were recruited from May to October 2012 in Xincai, Queshan and Weishi of Henan province. 6-months and 12-months follow-up programs were carried out after the regimen had been changed to AIDS second-line antiretroviral treatment, CD4⁺ T lymphocyte count, HIV-1 virus load and HIV-1 drug resistance were performed. Eighty-one cases of eligible patients were selected and followed by an amelioration of CD4 median at 6-month and 12-month follow-up period. Data showed that the baseline, 6-months and 12-months CD4 medians were 266 cells/µl, 275 cells/µl and 299 cells/µl (χ² = 8.214, P = 0.009). The ratio of HIV virus load suppression patients at 6-months and 12-months follow-up increased to 46.84% and 50.00%, respectively. Frequencies of HIV drug resistance also decreased at the baseline, 6-months and 12-months, with ratios as 66.67%, 26.58% and 27.63% (χ² = 29.362, P = 0.000), respectively. Ratios of patients that holding NRTI and NNRTI drug resistance appeared coinstantaneous decrease at the baseline, 6-months and 12-months, as 51.85%, 18.99% and 17.11% (χ² = 14.230, P = 0.005). At the baseline, the ratios of patients resisted to 3TC, ABC and FTC were all more than 50%, with AZT, D4T and DDI between 41%-44% while TDF appeared as 33.33%, then all of them declined to 12%-18% at the 6-month and 12-month follow-up periods. 65.43% of the patients resisted to both NVP and EFV but declined to 24%-27% at 6 months and 12 months. HCV/HIV co-infected patients experienced virological failure of AIDS first-line therapy were ameliorated after changing to use second-line antiretroviral treatment for 6-months, but did not show constant positive effect at the 12

  15. Live cumulative network meta-analysis: protocol for second-line treatments in advanced non-small-cell lung cancer with wild-type or unknown status for epidermal growth factor receptor

    PubMed Central

    Créquit, Perrine; Trinquart, Ludovic; Ravaud, Philippe

    2016-01-01

    Introduction Many second-line treatments for advanced non-small-cell lung cancer (NSCLC) have been assessed in randomised controlled trials, but which treatments work the best remains unclear. Novel treatments are being rapidly developed. We need a comprehensive up-to-date evidence synthesis of all these treatments. We present the protocol for a live cumulative network meta-analysis (NMA) to address this need. Methods and analysis We will consider trials of second-line treatments in patients with advanced NSCLC with wild-type or unknown epidermal growth factor receptor status. We will consider any single agent of cytotoxic chemotherapy, targeted therapy, combination of cytotoxic chemotherapy and targeted therapy and any combination of targeted therapies. The primary outcomes will be overall survival and progression-free survival. The live cumulative NMA will be initiated with a NMA and then iterations will be repeated at regular intervals to keep the NMA up-to-date over time. We have defined the update frequency as 4 months, based on an assessment of the pace of evidence production on this topic. Each iteration will consist of six methodological steps: adaptive search for treatments and trials, screening of reports and selection of trials, data extraction, assessment of risk of bias, update of the network of trials and synthesis, and dissemination. We will set up a research community in lung cancer, with different groups of contributors of different skills. We will distribute tasks through online crowdsourcing. This proof-of-concept study in second-line treatments of advanced NSCLC will allow one for assessing the feasibility of live cumulative NMA and opening the path for this new form of synthesis. Ethics and dissemination Ethical approval is not required because our study will not include confidential participant data and interventions. The description of all the steps and the results of this live cumulative NMA will be available online. Trial registration

  16. Virological Outcomes of Second-line Protease Inhibitor–Based Treatment for Human Immunodeficiency Virus Type 1 in a High-Prevalence Rural South African Setting: A Competing-Risks Prospective Cohort Analysis

    PubMed Central

    Collier, Dami; Iwuji, Collins; Derache, Anne; de Oliveira, Tulio; Okesola, Nonhlanhla; Calmy, Alexandra; Dabis, Francois; Pillay, Deenan

    2017-01-01

    Abstract Background. Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. Methods. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up. Results. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8–16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92–33.74]; P < .001). Conclusions. Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI

  17. Exposure-response relationship of ramucirumab in East Asian patients from RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer.

    PubMed

    Kim, Tae You; Yen, Chia-Jui; Al-Batran, Salah-Eddin; Ferry, David; Gao, Ling; Hsu, Yanzhi; Cheng, Rebecca; Orlando, Mauro; Ohtsu, Atsushi

    2017-06-20

    Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8 mg/kg or placebo in combination with 80 mg/m(2) paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure-response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial. Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (C min,ss) using a nonlinear mixed-effect modeling approach. Kaplan-Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (C min,ss) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively. Two hundred and twenty-two East Asian patients were included in this exposure-response analysis. Higher ramucirumab C min,ss was associated with longer overall survival (p = 0.0115) and progression-free survival (p = 0.0179) in this patient cohort. Patients with higher ramucirumab C min,ss (≥56.87 ng/ml median) had higher incidences of grade ≥3 leukopenia and neutropenia, but not febrile neutropenia or hypertension. This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure-response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer.

  18. Differential prognosis of metastatic colorectal cancer patients post-progression to first-line triplet chemotherapy plus bevacizumab, FIr-B/FOx, according to second-line treatment and KRAS genotype

    PubMed Central

    BRUERA, GEMMA; CANNITA, KATIA; GIORDANO, ALDO VICTOR; VICENTINI, ROBERTO; FICORELLA, CORRADO; RICEVUTO, ENRICO

    2014-01-01

    Clinical outcome post-progression to first-line triplet chemotherapy (CT) plus bevacizumab (FIr-B/FOx) was evaluated in metastatic colorectal cancer (MCRC) patients (pts). Second-line treatment was selected according to fitness, KRAS genotype, previous efficacy and safety. Efficacy was evaluated and compared according to treatment or KRAS genotype, using log-rank analysis. Among 54 pts, median overall survival (OS) post-progression was 12 months, significantly better in 40 (74.1%) treated compared to 14 (25.9%) who died without further treatment. Second-line surgical treatment, 4 pts (7.4%), medical treatment, 36 pts (66.7%): triplet CT plus targeted agent, 10 (18.5%); triplet regimens, 19 (35.2%); doublet/monotherapy, 7 (13%). At follow-up of 14 months, objective response rate (ORR) was 38%, metastasectomies 12.5%, progression-free survival (PFS) 10 months, OS 14 months. According to treatment, ORR, metastasectomies, PFS and OS were significantly favourable in triplet CT plus targeted agent compared to triplet, respectively: 80%, 40%, 13 months, not reached; 28%, 6%, 8 months, 11 months. PFS and OS were significantly worse in c.35 G>A mutant compared to wild-type and/or other mutant patients. Prognosis after progression to first-line FIr-B/FOx may be significantly favourable in MCRC pts re-challenged with intensive regimens, and unfavourable in c.35 G>A KRAS mutant patients. PMID:24247407

  19. A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer

    PubMed Central

    Kroeber, Vinzenz; Nagel, Sylke; Schuette, Wolfgang; Blankenburg, Thomas

    2014-01-01

    Introduction Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. Methods Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200–300 mg/m2 followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m2. Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. Results The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. Conclusions We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered. PMID:25126073

  20. A Prospective Phase I/II Study: Combination Chemotherapy with Docetaxel and Pemetrexed as Second-Line Treatment in Patients with Stage IIIB/IV Non-Small Cell Lung Cancer.

    PubMed

    Kroeber, Vinzenz; Nagel, Sylke; Schuette, Wolfgang; Blankenburg, Thomas

    2014-05-01

    Two standard single-agent chemotherapy treatments (docetaxel and pemetrexed) were combined in this trial and administered as second-line treatment in patients with non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and feasibility of combining docetaxel with pemetrexed. Six patients were enrolled between August 2007 and March 2009 with stage IIIB/IV NSCLC. The dose-escalation model included a pemetrexed infusion on day 1 of 200-300 mg/m(2) followed by infusion of docetaxel on days 1, 8 and 15 at doses from 20 to 30 mg/m(2). Primary study endpoints included efficacy and safety variables, also progression-free, overall and 1-year survival and time to progression. The study was abandoned due to adverse effects defined in the protocol. The major toxicities were all of grade 3 and included fatigue, stomatitis/mucositis, diarrhea and in one case, an episode of febrile neutropenia. Two patients died during the study, but not as a direct result of the treatment. We recommend that docetaxel or pemetrexed monotherapies should continue to be considered the standard second-line chemotherapy treatment against NSCLC. The results of this study warrant no further investigation into this particular combination treatment due to the severe toxicity effects encountered.

  1. Randomised, multicentre trial of micafungin vs. an institutional standard regimen for salvage treatment of invasive aspergillosis.

    PubMed

    Cornely, Oliver A; Meems, Lambertus; Herbrecht, Raoul; Viscoli, Claudio; van Amsterdam, Ronald G M; Ruhnke, Markus

    2015-01-01

    Invasive aspergillosis remains associated with significant morbidity and mortality, necessitating new options for salvage therapy. The objective of this study was to evaluate the efficacy and safety of micafungin as salvage monotherapy in patients with invasive aspergillosis. Patients with proven or probable invasive aspergillosis, who were refractory or intolerant to previous systemic antifungal therapy, were randomised 2 : 1 to receive 300 mg day(-1) intravenous micafungin monotherapy or an intravenous control monotherapy [lipid amphotericin B (5 mg kg(-1) day(-1)), voriconazole (8 mg kg(-1) day(-1)) or caspofungin (50 mg day(-1))] for 3-12 weeks. Patients underwent final assessment 12 weeks after treatment start. Seventeen patients with invasive aspergillosis (proven, n = 2; probable, n = 14; not recorded, n = 1) participated in the study (micafungin arm, n = 12; control arm, n = 5). Three patients each in the micafungin (25.0%; 95% CI: 5.5-57.2) and control arm (60.0%; 95% CI: 14.7-94.7) had successful therapy at end of treatment as assessed by an Independent Data Review Board. Eleven patients died; six due to invasive aspergillosis. No deaths were considered related to study treatment. During this study it became increasingly common to use combination treatment for salvage therapy. Consequently, enrolment was low and the study was discontinued early. No clear trends in efficacy and safety can be concluded.

  2. Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer.

    PubMed

    Carrato, A; Gómez, A; Escudero, P; Chaves, M; Rivera, F; Marcuello, E; González, E; Grávalos, C; Constenla, M; Manzano, J Luis; Losa, F; Maurel, J; Dueñas, R; Massuti, B; Gallego, J; Aparicio, J; Antón, A; Aranda, E

    2013-09-01

    To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.

  3. Salvage endoscopic resection as a treatment for locoregional failure or recurrence following chemoradiotherapy or radiotherapy for esophageal cancer

    PubMed Central

    NAKAMURA, RIEKO; OMORI, TAI; TAKEUCHI, HIROYA; KAWAKUBO, HIROFUMI; TAKAHASHI, TSUNEHIRO; WADA, NORIHITO; SAIKAWA, YOSHIRO; KITAGAWA, YUKO

    2016-01-01

    Radiotherapy (RT) or chemoradiotherapy (CRT) is a potentially curative, non-surgical treatment option for esophageal cancer, although the rate of local failure within the esophagus remains relatively high. Salvage esophagectomy is not regarded as a common treatment for esophageal cancer, since it is a high-risk surgery with a relatively high surgical mortality rate. Salvage endoscopic resection (ER) for local failure is used for treatment when esophageal cancer is localized and superficial. To evaluate to usefulness of salvage ER, the present study reviewed the clinicopathological records and follow-up data of 37 patients that underwent salvage ER for esophageal cancer, following initial treatment with RT or CRT. Salvage ER was conducted on a total of 78 lesions observed in the 37 patients. Since a thick epithelium and lack of normal vessels on the surface of the mucosa are characteristics of esophageal mucosa following RT or CRT, almost all the lesions were detected using iodine dyeing, and not by narrow band imaging. The growth rate of the detected lesions was relatively high, and early treatment was required. No particular complications occurred during the endoscopic treatment. A total of 11 patients survived for >5 years subsequent to initial endoscopic treatment. Only 4 patients succumbed to esophageal cancer. In conclusion, the present study demonstrated that salvage ER following CRT or RT for esophageal cancer is a minimally invasive, safe, adaptive and curative method for superficial lesions without distant metastases in patients with esophageal cancer with local failure following CRT or RT. PMID:27284365

  4. Impact of Recurrence and Salvage Surgery on Survival After Multidisciplinary Treatment of Rectal Cancer.

    PubMed

    Ikoma, Naruhiko; You, Y Nancy; Bednarski, Brian K; Rodriguez-Bigas, Miguel A; Eng, Cathy; Das, Prajnan; Kopetz, Scott; Messick, Craig; Skibber, John M; Chang, George J

    2017-08-10

    Purpose After preoperative chemoradiotherapy followed by total mesorectal excision for locally advanced rectal cancer, patients who experience local or systemic relapse of disease may be eligible for curative salvage surgery, but the benefit of this surgery has not been fully investigated. The purpose of this study was to characterize recurrence patterns and investigate the impact of salvage surgery on survival in patients with rectal cancer after receiving multidisciplinary treatment. Patients and Methods Patients with locally advanced (cT3-4 or cN+) rectal cancer who were treated with preoperative chemoradiotherapy followed by total mesorectal excision at our institution during 1993 to 2008 were identified. We examined patterns of recurrence location, time to recurrence, treatment factors, and survival. Results A total of 735 patients were included. Tumors were mostly midrectal to lower rectal cancer, with a median distance from the anal verge of 5.0 cm. The most common recurrence site was the lung followed by the liver. Median time to recurrence was shorter in liver-only recurrence (11.2 months) than in lung-only recurrence (18.2 months) or locoregional-only recurrence (24.7 months; P = .001). Salvage surgery was performed in 57% of patients with single-site recurrence and was associated with longer survival after recurrence in patients with lung-only and liver-only recurrence ( P < .001) but not in those with locoregional-only recurrence ( P = .353). Conclusion We found a predilection for lung recurrence in patients with rectal cancer after multidisciplinary treatment. Salvage surgery was associated with prolonged survival in patients with lung-only and liver-only recurrence, but not in those with locoregional recurrence, which demonstrates a need for careful consideration of the indications for resection.

  5. Real-world treatment patterns for patients receiving second-line and third-line treatment for advanced non-small cell lung cancer: A systematic review of recently published studies.

    PubMed

    Davies, Jessica; Patel, Manali; Gridelli, Cesare; de Marinis, Filippo; Waterkamp, Daniel; McCusker, Margaret E

    2017-01-01

    Most patients with advanced non-small cell lung cancer (NSCLC) have a poor prognosis and receive limited benefit from conventional treatments, especially in later lines of therapy. In recent years, several novel therapies have been approved for second- and third-line treatment of advanced NSCLC. In light of these approvals, it is valuable to understand the uptake of these new treatments in routine clinical practice and their impact on patient care. A systematic literature search was conducted in multiple scientific databases to identify observational cohort studies published between January 2010 and March 2017 that described second- or third-line treatment patterns and clinical outcomes in patients with advanced NSCLC. A qualitative data synthesis was performed because a meta-analysis was not possible due to the heterogeneity of the study populations. A total of 12 different study cohorts in 15 articles were identified. In these cohorts, single-agent chemotherapy was the most commonly administered treatment in both the second- and third-line settings. In the 5 studies that described survival from the time of second-line treatment initiation, median overall survival ranged from 4.6 months (95% CI, 3.8-5.7) to 12.8 months (95% CI, 10.7-14.5). There was limited information on the use of biomarker-directed therapy in these patient populations. This systematic literature review offers insights into the adoption of novel therapies into routine clinical practice for second- and third-line treatment of patients with advanced NSCLC. This information provides a valuable real-world context for the impact of recently approved treatments for advanced NSCLC.

  6. Survival outcome of salvage hepatectomy in patients with local, recurrent hepatocellular carcinoma who underwent radiofrequency ablation as their first treatment.

    PubMed

    Ueno, Masaki; Nakai, Takuya; Hayashi, Michihiro; Hirokawa, Fumitoshi; Nagano, Hiroaki; Wada, Hiroshi; Kaibori, Masaki; Matsui, Kosuke; Tanaka, Shogo; Yamaue, Hiroki; Kubo, Shoji

    2016-09-01

    Local recurrence is a specific problem after radiofrequency ablation of small hepatocellular carcinoma, and additional treatment is an important issue. We aimed to investigate the outcome of salvage hepatectomy in patients who develop local, recurrent hepatocellular carcinoma after treatment with radiofrequency ablation. From 2001-2013, we reviewed 58 patients from 6 university hospitals with local, recurrent hepatocellular carcinoma who underwent salvage hepatectomy after their initial radiofrequency ablation treatment. Pathologic characteristics and prognostic factors influencing overall survival were analyzed. Noncurative resection, des-gamma carboxy prothrombin levels >40 mAU/mL, and multiple preceding treatments before salvage hepatectomy were negative prognostic factors for overall survival. The 5-year survivals for the prognostic factors were 0%, 24%, and 30%, respectively, after salvage hepatectomy, and 0%, 54%, and 54% after initial radiofrequency ablation treatment, respectively. As for the pathologic finding of local, recurrent hepatocellular carcinoma after radiofrequency ablation, vascular invasion was observed frequently in patients with increases in des-gamma carboxy prothrombin levels and with multiple preceding treatments before salvage hepatectomy with a frequency of 59% and 53%, respectively (P < .01 and .05). Noncurative resection, increases in serum des-gamma carboxy prothrombin, and multiple preceding treatments were prognostic factors for subsequent salvage hepatectomy; nevertheless, survival outcomes were still acceptable when a curative salvage hepatectomy was performed. Increases in serum des-gamma carboxy prothrombin and multiple preceding treatments were positive predictors for pathologic vascular invasion. These factors should be taken into consideration when selecting treatment modalities for locally recurrent hepatocellular carcinoma following radiofrequency ablation. Repetition of unsuccessful, loco-regional treatment would appear

  7. High-dose chemotherapy as salvage treatment in germ-cell cancer: when, in whom and how.

    PubMed

    Lorch, Anja; Beyer, Jörg

    2016-09-27

    Over the past two decades, the use of well-validated, guideline-based strategies resulted in high cure rates in patients with germ-cell cancer (GCC) often despite widespread metastatic disease at initial presentation. Yet, about 30 % of patients diagnosed with metastatic disease corresponding to about 5-10 % of GCC patients overall will experience disease progression or recurrence at some time point of their disease with the need for salvage treatment. Salvage treatment is more complex and less well validated than first-line treatment: Its rare patient cohorts are more heterogeneous and prognostic factors impact more compared to other treatment scenarios. In patients with metastatic GCC, there are several scenarios in which first-line treatment strategies can fail (Fig. 1). Prior to initiation of any salvage treatment, several considerations have to be made, which will be addressed in this review: verification that first-line treatment has indeed failed, estimation of the adequacy and the effectiveness of first-line treatment, search for metastatic sites and extent of disease recurrence, assessment of known prognostic factors and finally the choice of the optimal salvage strategy taking into account the aforementioned variables. High-dose chemotherapy will be a rational choice for many patients in need of salvage treatment, but careful patient selection will be required to avoid overtreatment and unnecessary long-term toxicity.

  8. Nintedanib in combination with docetaxel for second-line treatment of advanced non-small-cell lung cancer; GENESIS-SEFH drug evaluation report.

    PubMed

    Espinosa Bosch, María; Asensi Diez, Rocío; García Agudo, Sara; Clopes Estela, Ana

    2016-06-01

    Nintedanib is a triple angiokinase inhibitor that has been approved by the European Agency Medicines (EMA) in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non small cell lung cancer (NSCLC) of adenocarcinoma tumour histology, after first-line chemotherapy. In LUME-Lung 1 clinical trial, the combination of nintedanib plus docetaxel vs. placebo plus docetaxel improved progression free survival (PFS) in NSCLC patients, and improved overall survival in the population of adenocarcinoma patients, particularly in those with progression within 9 months after first line treatment initiation, median 10.9 months ( [95% CI 8.5-12.6] vs. 7.9 months [6.7-9.1]; HR 0.75 [95% CI 0.60-0.92], p=0.0073). The toxicity profile of the combination included a higher incidence of neutropenia, gastro-intestinal (GI) disorders, and liver enzyme elevations; however, this did not cause a detrimental effect on patient quality of life. According to data from the clinical trial mentioned, the addition of nintedanib to docetaxel would lead to an estimated incremental cost-effectiveness ratio (ICER) per year of life with PFS in the overall population of 134,274.47 € (notified price). In the adenocarcinoma population per each life of year gained (LYG), the ICER of adding nintedanib to docetaxel would be 40,886.14 €; while by implementing a sensitivity analysis with a 25% discount in the drug price, the cost per LYG would be 32,364.05 €, and would place it close to the threshold of cost-effectiveness usually considered acceptable in our setting. In view of efficacy and safety results the proposed positioning is to recommend its inclusion in the Hospital Formulary only for adult patients with metastatic or locally recurrent NSCLC with adenocarcinoma histology after first line chemotherapy, with progression < 9 months from the initiation of first line treatment, taking into account the inclusion and exclusion criteria in the

  9. Efficacy of tacrolimus 0.03% ointment as second-line treatment for children with moderate-to-severe atopic dermatitis: evidence from a randomized, double-blind non-inferiority trial vs. fluticasone 0.005% ointment.

    PubMed

    Doss, N; Kamoun, M-R; Dubertret, L; Cambazard, F; Remitz, A; Lahfa, M; de Prost, Y

    2010-03-01

    Tacrolimus 0.03% ointment is licensed for second-line treatment of children with atopic dermatitis (AD). Although data are available from clinical trials, no study has enrolled only second-line patients. This double-blind, non-inferiority study compared tacrolimus 0.03% and fluticasone 0.005% ointments in children with moderate-to-severe AD, who had responded insufficiently to conventional therapies. Children (aged 2-15 yr) were randomized to tacrolimus ointment (n = 240) or fluticasone ointment (n = 239), twice daily until clearance or for a maximum of 3 wk and, if lesions remained, once daily for up to 3 wk further. Primary end-point was week 3 response rate (improvement of >or=60% in modified Eczema Area and Severity Index and not withdrawn for lack of efficacy). Secondary end-points included pruritus and sleep quality, global assessment of clinical response, incidence of new flares and safety. Response rates were 86.3% with tacrolimus ointment and 91.5% with fluticasone. Lower limit of the 95% confidence interval was -11.8%, exceeding the non-inferiority limit of -15% and meeting the primary end-point. Moderate or better improvement on the physicians' global assessment occurred in 93.6% and 92.4% of patients in the tacrolimus ointment and fluticasone arms, respectively, while median pruritus scores improved by 84.0% and 91.5%. Sleep quality improved by approximately 92% in both treatment arms. After day 21, new flare-up occurred in 5.5% and 11.3% of patients receiving tacrolimus ointment and fluticasone, respectively; mean times to new flares were 6.5 +/- 5.0 and 8.6 +/- 5.2 days. Adverse events were similar between the two arms, with the exception of application-site skin burning sensation in the tacrolimus ointment group. In conclusion, efficacy of tacrolimus 0.03% ointment as second-line treatment was not inferior to that of fluticasone 0.005% ointment, with similar benefits on global disease improvement and quality of sleep.

  10. Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer.

    PubMed

    Tabernero, Josep; Ohtsu, Atsushi; Muro, Kei; Van Cutsem, Eric; Oh, Sang Cheul; Bodoky, György; Shimada, Yasuhiro; Hironaka, Shuichi; Ajani, Jaffer A; Tomasek, Jiri; Safran, Howard; Chandrawansa, Kumari; Hsu, Yanzhi; Heathman, Michael; Khan, Azhar; Ni, Lan; Melemed, Allen S; Gao, Ling; Ferry, David; Fuchs, Charles S

    2017-10-01

    Ramucirumab is an IgG1 monoclonal antibody specific for the vascular endothelial growth factor receptor-2. Ramucirumab, 8 mg/kg every 2 weeks, administered as monotherapy (REGARD) or in combination with paclitaxel (RAINBOW), was safe and effective in patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer. We evaluated exposure-efficacy and exposure-safety relationships of ramucirumab from two randomized, placebo-controlled phase III trials. Sparse pharmacokinetic samples were collected, and a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (Cmin,ss). Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the ramucirumab exposure (Cmin,ss)-efficacy relationship to overall survival (OS) and progression-free survival (PFS). Logistic regression analyses were used to evaluate exposure-safety relationships. Analyses included 321 ramucirumab + paclitaxel and 335 placebo + paclitaxel patients from RAINBOW and 72 ramucirumab and 35 placebo patients from REGARD. Exposure-efficacy analysis showed ramucirumab Cmin,ss was a significant predictor of OS and PFS in both trials. Higher ramucirumab exposure was associated with longer OS and PFS. In RAINBOW, grade ≥3 hypertension, leukopenia, and neutropenia, but not febrile neutropenia, significantly correlated with Cmin,ss, with increased exposure leading to increased incidence. Exploratory exposure-response analyses suggest a positive relationship between efficacy and ramucirumab exposure with manageable toxicities at exposures generated from a dose of 8 mg/kg ramucirumab given every 2 weeks for patients with advanced gastric/GEJ cancer. These findings suggest an opportunity to further optimize benefit versus risk profiles of ramucirumab treatment in patients with gastric/GEJ cancer. Mol Cancer Ther; 16(10); 2215-22. ©2017 AACR. ©2017 American Association for Cancer Research.

  11. Early outcomes and the virologic impact of delayed treatment switching on second-line therapy in an antiretroviral roll-out program in South Africa

    PubMed Central

    Levison, Julie H.; Orrell, Catherine; Losina, Elena; Lu, Zhigang; Freedberg, Kenneth A.; Wood, Robin

    2011-01-01

    Background More patients in resource-limited settings are starting 2nd-line ART following 1st-line ART failure. We aimed to describe predictors of lack of virologic suppression in HIV-infected patients on 2nd-line ART in a roll-out program in South Africa. Methods Retrospective analysis was performed on an adult HIV treatment cohort who started 2nd-line ART (lopinavir/ritonavir, didanosine, and zidovudine) after virologic failure of 1st-line ART (2 consecutive HIV RNA >1000 copies/ml). Predictors of week-24 lack of suppression (HIV RNA > 400 copies/ml) on 2nd-line ART were determined by bivariate analysis where missing equals failure. A multivariable model adjusted for gender, age, and time to ART switch. We tested these findings in sensitivity analyses defining lack of suppression at week-24 as HIV RNA > 1000 and > 5000 copies/ml. Results Of 6,339 patients on ART, 202 started 2nd-line ART. At week-24 an estimated 41% (95% CI 34–47%) did not achieve virologic suppression. Female sex (adjusted OR=2.25; 95% CI, 1.03–4.88) and time to ART switch, (adjusted OR=1.07; 95% CI, 1.01–1.14 for each additional month) increased the risk of lack of virologic suppression. Age, CD4 count, and HIV RNA at 2nd-line ART initiation did not predict this outcome. In multivariate models, these findings were insensitive to the definition of lack of virologic suppression. Conclusions A substantial number of HIV-infected patients do not achieve virologic suppression by week-24 of 2nd-line ART. Women and patients with delayed start of 2nd-line ART after 1st-line ART failure were at an increased risk of lack of virologic suppression. PMID:21900717

  12. Randomized phase II study of axitinib versus placebo plus best supportive care in second-line treatment of advanced hepatocellular carcinoma.

    PubMed

    Kang, Y-K; Yau, T; Park, J-W; Lim, H Y; Lee, T-Y; Obi, S; Chan, S L; Qin, Sk; Kim, R D; Casey, M; Chen, C; Bhattacharyya, H; Williams, J A; Valota, O; Chakrabarti, D; Kudo, M

    2015-12-01

    The efficacy and safety of axitinib, a potent and selective vascular endothelial growth factor receptors 1-3 inhibitor, combined with best supportive care (BSC) was evaluated in a global, randomized, placebo-controlled phase II trial in patients with locally advanced or metastatic hepatocellular carcinoma (HCC). Patients with HCC and Child-Pugh Class A who progressed on or were intolerant to one prior antiangiogenic therapy were stratified by tumour invasion (presence/absence of extrahepatic spread and/or vascular invasion) and region (Asian/non-Asian) and randomized (2:1) to axitinib/BSC (starting dose 5 mg twice-daily) or placebo/BSC. The primary end point was overall survival (OS). The estimated hazard ratio for OS was 0.907 [95% confidence interval (CI) 0.646-1.274; one-sided stratified P = 0.287] for axitinib/BSC (n = 134) versus placebo/BSC (n = 68), with the median (95% CI) of 12.7 (10.2-14.9) versus 9.7 (5.9-11.8) months, respectively. Results of prespecified subgroup analyses in Asian versus non-Asian patients or presence versus absence of tumour invasion were consistent with the overall population. Improvements favouring axitinib/BSC (P < 0.01) were observed in secondary efficacy end point analyses [progression-free survival (PFS), time to tumour progression (TTP), and clinical benefit rate (CBR)], and were retained among Asian patients in the prespecified subgroup analyses. Overall response rate did not differ significantly between treatments and patient-reported outcomes favoured placebo/BSC. Most common all-causality adverse events with axitinib/BSC were diarrhoea (54%), hypertension (54%), and decreased appetite (47%). Baseline serum analyses identified potential new prognostic (interleukin-6, E-selectin, interleukin-8, angiopoietin-2, migration inhibitory factor, and c-MET) or predictive (E-selectin and stromal-derived factor-1) factors for survival. Axitinib/BSC did not improve OS over placebo/BSC in the overall population or in stratification

  13. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer

    PubMed Central

    Heymach, J. V.; Lockwood, S. J.; Herbst, R. S.; Johnson, B. E.; Ryan, A. J.

    2014-01-01

    Background ZODIAC was a randomized phase III study of second-line treatment in patients with advanced non-small cell lung cancer (NSCLC) that evaluated the addition of vandetanib to docetaxel. The study showed a statistically significant improvement in progression-free survival and objective response rate, but not in overall survival for unselected patients. This study evaluated epidermal growth factor receptor (EGFR) gene mutation, copy number gain, and protein expression, and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers predicting benefit from vandetanib as second-line treatment of NSCLC. Patients and methods After progression following first-line chemotherapy, 1391 patients with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1 to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m2 every 21 days) or placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were collected from consenting patients (n = 958) for predefined, prospective biomarker analyses. Results Of evaluable samples, 14% were EGFR mutation positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive, and 13% were KRAS mutation positive. Compared with the overall study population, in which progression-free survival (PFS) [hazard ratio (HR) = 0.79] but not OS (HR = 0.91) were significantly improved with vandetanib, there was greater relative clinical benefit for patients with EGFR mutation-positive tumors [PFS HR 0.51, confidence interval (CI) 0.25–1.06 and OS HR 0.46, CI 0.14–1.57] and EGFR FISH-positive tumors (PFS HR 0.61, CI 0.39–0.94 and OS HR 0.48, CI 0.28–0.84). Similarly, patients with EGFR mutation or FISH-positive tumor samples who received vandetanib had an increased chance of objective tumor response (odds ratios 3.34, CI 0.8–13.89, and 3.90, CI 1.02–14.82, respectively). There did not appear to be benefit for vandetanib in patients with KRAS mutation-positive tumors. Conclusions

  14. EGFR biomarkers predict benefit from vandetanib in combination with docetaxel in a randomized phase III study of second-line treatment of patients with advanced non-small cell lung cancer.

    PubMed

    Heymach, J V; Lockwood, S J; Herbst, R S; Johnson, B E; Ryan, A J

    2014-10-01

    ZODIAC was a randomized phase III study of second-line treatment in patients with advanced non-small cell lung cancer (NSCLC) that evaluated the addition of vandetanib to docetaxel. The study showed a statistically significant improvement in progression-free survival and objective response rate, but not in overall survival for unselected patients. This study evaluated epidermal growth factor receptor (EGFR) gene mutation, copy number gain, and protein expression, and KRAS gene mutation, in pretreatment tumor samples as potential biomarkers predicting benefit from vandetanib as second-line treatment of NSCLC. After progression following first-line chemotherapy, 1391 patients with locally advanced or metastatic (stage IIIB/IV) NSCLC were randomized 1 : 1 to receive vandetanib (100 mg/day) plus docetaxel (75 mg/m(2) every 21 days) or placebo plus docetaxel in the ZODIAC study. Archival tumor samples (n = 570) were collected from consenting patients (n = 958) for predefined, prospective biomarker analyses. Of evaluable samples, 14% were EGFR mutation positive, 35% were EGFR FISH positive, 88% were EGFR protein expression positive, and 13% were KRAS mutation positive. Compared with the overall study population, in which progression-free survival (PFS) [hazard ratio (HR) = 0.79] but not OS (HR = 0.91) were significantly improved with vandetanib, there was greater relative clinical benefit for patients with EGFR mutation-positive tumors [PFS HR 0.51, confidence interval (CI) 0.25-1.06 and OS HR 0.46, CI 0.14-1.57] and EGFR FISH-positive tumors (PFS HR 0.61, CI 0.39-0.94 and OS HR 0.48, CI 0.28-0.84). Similarly, patients with EGFR mutation or FISH-positive tumor samples who received vandetanib had an increased chance of objective tumor response (odds ratios 3.34, CI 0.8-13.89, and 3.90, CI 1.02-14.82, respectively). There did not appear to be benefit for vandetanib in patients with KRAS mutation-positive tumors. High EGFR gene copy number or activating EGFR mutations may

  15. Salvage prostatectomy for post-radiation adenocarcinoma with treatment effect: Pathological and oncological outcomes.

    PubMed

    Metcalfe, Michael J; Troncoso, Patricia; Guo, Charles C; Chen, Hsiang-Chun; Bozkurt, Yasar; Ward, John F; Pisters, Louis L

    2017-07-01

    Prostate biopsies following localized radiation therapy for prostate cancer often demonstrate residual prostatic carcinoma with treatment effect (CTE). The final oncological outcome of prostatic CTE is currently uncertain. We studied the pathological and oncological outcomes for a large cohort of patients who had CTE on post-radiation therapy biopsy and subsequently underwent salvage radical prostatectomy (SRP). A single-centre retrospective review of all SRPs performed from 1995-2014 was performed. Cases were selected for this analysis if they had had a post-radiation "for-cause" biopsy. Biopsy results were compared to final pathology results following SRP. Pathological and clinical outcomes were compared by extent of treatment effect seen on the post-radiation biopsy. A total of 70 patients who had salvage prostatectomy at MD Anderson Cancer Centre from 2007-2015 met study criteria. CTE was found on biopsy in the absence of other adenocarcinoma in 16 patients. Among them, one (7%) patient had no evidence of carcinoma at the time of salvage prostatectomy, four (27%) had CTE, three (20%) had adenocarcinoma with minimal or partial treatment effect (PTE), and seven (47%) had adenocarcinoma with no treatment effect (NTE). For those with CTE on biopsy, 69% had biochemical recurrence at a median time of 0.4 years (interquartile range [IQR] 0.22-1.52) vs. 52% for all patients (median 0.44 years, IQR 0.11-1.70) and 47% for those with no treatment effect (median 0.62 years, IQR 0.05-1.90). Metastasis developed after salvage prostatectomy in 11.8% of the whole cohort (8/68, median time to metastasis was 3.03 years, IQR 2.45-4.47), 26.7% of patients with CTE (median 3.2 years, IQR 1.96-4.44), and 6.7% of patients with NTE (median 2.45 years, IQR 0.98-2.86). Median recurrence-free survival was 2.78 years (95% confidence interval [CI] 0.84-5.43) for all patients, 0.51 years (95% CI 0.22-2.35) for those with CTE, and 4.95 years (95% CI 0.95-7.08) for those with NTE; the

  16. Salvage treatment with apatinib for advanced non-small-cell lung cancer

    PubMed Central

    Song, Zhengbo; Yu, Xinmin; Lou, Guangyuan; Shi, Xun; Zhang, Yiping

    2017-01-01

    Objective No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment. Methods We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method. Results Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%. Conclusion Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment. PMID:28367065

  17. Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

    PubMed Central

    Selle, F.; Gligorov, J.; Richard, S.; Khalil, A.; Alexandre, I.; Avenin, D.; Provent, S.; Soares, D.G.; Lotz, J.P.

    2014-01-01

    Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis. PMID:25493378

  18. Potential health gains for patients with metastatic renal cell carcinoma in daily clinical practice: A real-world cost-effectiveness analysis of sequential first- and second-line treatments.

    PubMed

    De Groot, S; Blommestein, H M; Redekop, W K; Sleijfer, S; Kiemeney, L A L M; Oosterwijk, E; Uyl-de Groot, C A

    2017-01-01

    Randomised controlled trials have shown that targeted therapies like sunitinib are effective in metastatic renal cell carcinoma (mRCC). Little is known about the current use of these therapies, and their associated costs and effects in daily clinical practice. We estimated the real-world cost-effectiveness of different treatment strategies comprising one or more sequentially administered drugs. Analyses were performed using patient-level data from a Dutch population-based registry including patients diagnosed with primary mRCC from January 2008 to December 2010 (i.e., treated between 2008 and 2013). The full disease course of these patients was estimated using a patient-level simulation model based on regression analyses of the registry data. A healthcare sector perspective was adopted; total costs included healthcare costs related to mRCC. Cost-effectiveness was expressed in cost per life-year and cost per quality-adjusted life-year (QALY) gained. Probabilistic sensitivity analysis was conducted to estimate the overall uncertainty surrounding cost-effectiveness. In current daily practice, 54% (336/621) of all patients was treated with targeted therapies. Most patients (84%; 282/336) received sunitinib as first-line therapy. Of the patients receiving first-line therapy, 30% (101/336) also received second-line therapy; the majority was treated with everolimus (40%, 40/101) or sorafenib (28%, 28/101). Current treatment practice (including patients not receiving targeted therapy) led to 0.807 QALYs; mean costs were €58,912. This resulted in an additional €105,011 per QALY gained compared to not using targeted therapy at all. Forty-six percent of all patients received no targeted therapy; of these patients, 24% (69/285) was eligible for sunitinib. If these patients were treated with first-line sunitinib, mean QALYs would improve by 0.062-0.076 (where the range reflects the choice of second-line therapy). This improvement is completely driven by the health gain seen

  19. [Usefulness of endoscopic salvage treatment in a patient with local failure esophageal cancer after CRT].

    PubMed

    Higashino, Koji; Hanafusa, Masao; Ishihara, Ryu

    2011-11-01

    Chemoradiotherapy (CRT) is widely used as non-surgical treatment for esophageal cancer in recent years. CRT is very useful, but it allows about 40% relapse. Salvage surgery after CRT, long-term survival can be expected, but perioperative mortality is high. In contrast, EMR for local failure after definitive CRT has been reported showing a 5-year survival rate of 49. 1%. If it can safely control of local failure, then we thought it's useful for long-term survival. If the depth of invasion was to the submucosal layer of the local failure lesion, we performed an endoscopic resection. If vertical margins are positive pathologically, we have added a photodynamic therapy. In cases of difficult endoscopic resection, PDT alone was performed. We experienced a case of recurrent esophageal cancer after CRT was useful for local treatment with PDT and EMR.

  20. Preliminary Experience in Treatment of Papillary and Macular Retinoblastoma: Evaluation of Local Control and Local Complications After Treatment With Linear Accelerator-Based Stereotactic Radiotherapy With Micromultileaf Collimator as Second-Line or Salvage Treatment After Chemotherapy

    SciTech Connect

    Pica, Alessia; Moeckli, Raphael; Balmer, Aubin; Beck-Popovic, Maja; Chollet-Rivier, Madeleine; Do, Huu-Phuoc; Weber, Damien C.; Munier, Francis L.

    2011-12-01

    Purpose: To determine the local control and complication rates for children with papillary and/or macular retinoblastoma progressing after chemotherapy and undergoing stereotactic radiotherapy (SRT) with a micromultileaf collimator. Methods and Materials: Between 2004 and 2008, 11 children (15 eyes) with macular and/or papillary retinoblastoma were treated with SRT. The mean age was 19 months (range, 2-111). Of the 15 eyes, 7, 6, and 2 were classified as International Classification of Intraocular Retinoblastoma Group B, C, and E, respectively. The delivered dose of SRT was 50.4 Gy in 28 fractions using a dedicated micromultileaf collimator linear accelerator. Results: The median follow-up was 20 months (range, 13-39). Local control was achieved in 13 eyes (87%). The actuarial 1- and 2-year local control rates were both 82%. SRT was well tolerated. Late adverse events were reported in 4 patients. Of the 4 patients, 2 had developed focal microangiopathy 20 months after SRT; 1 had developed a transient recurrence of retinal detachment; and 1 had developed bilateral cataracts. No optic neuropathy was observed. Conclusions: Linear accelerator-based SRT for papillary and/or macular retinoblastoma in children resulted in excellent tumor control rates with acceptable toxicity. Additional research regarding SRT and its intrinsic organ-at-risk sparing capability is justified in the framework of prospective trials.

  1. Treatment patterns, overall survival, healthcare resource use and costs in elderly Medicare beneficiaries with chronic myeloid leukemia using second-generation tyrosine kinase inhibitors as second-line therapy.

    PubMed

    Smith, B Douglas; Liu, Jun; Latremouille-Viau, Dominick; Guerin, Annie; Fernandez, Daniel; Chen, Lei

    2016-05-01

    Objective Though the median age at diagnosis is 64 years, few studies focus on elderly (≥65 years) patients with chronic myeloid leukemia (CML). This study examines healthcare outcomes among elderly Medicare beneficiaries with CML who started nilotinib or dasatinib after imatinib. Research design and methods Patients were identified in the Medicare Research Identifiable Files (2006-2012) and had continuous Medicare Parts A, B, and D coverage. Main outcome measures Treatment patterns, overall survival (OS), monthly healthcare resource utilization and medical costs were measured from the second-line tyrosine kinase inhibitor (TKI) initiation (index date) to end of Medicare coverage. Results Despite similar adherence, dasatinib patients (N = 379) were more likely to start on the recommended dose (74% vs. 53%; p < 0.001), and to have dose reductions (21% vs. 11%, adjusted hazard ratio [HR] = 1.94; p = 0.002) or dose increases (9% vs. 7%; adjusted HR = 1.81; p = 0.048) than nilotinib patients (N = 280). Fewer nilotinib patients discontinued (59% vs. 67%; adjusted HR = 0.80; p = 0.026) or switched to another TKI (21% vs. 29%; adjusted HR = 0.72; p = 0.044) than dasatinib patients. Nilotinib patients had longer median OS (>4.9 years vs. 4.0 years; p = 0.032) and 37% lower mortality risk than dasatinib patients (adjusted HR = 0.63; p = 0.008). Nilotinib patients had 23% fewer inpatient admissions, 30% fewer emergency room visits, 13% fewer outpatient visits (all p < 0.05), and lower monthly medical costs (by $513, p = 0.024) than dasatinib patients. Limitations Lack of clinical assessment (disease phase and response to first-line therapy) and retrospective nature of study (unobservable potential confounding factors, non-randomized treatment choice). Conclusions In the current study of elderly CML patients, initiation of second-line TKIs frequently occurs at doses lower than the recommended starting doses and

  2. Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab)

    PubMed Central

    Tam, Constantine S.; O’Brien, Susan; Plunkett, William; Wierda, William; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim-Anh; Cortes, Jorge; Khouri, Issa; Kantarjian, Hagop; Lerner, Susan

    2014-01-01

    Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care. PMID:25281606

  3. Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab).

    PubMed

    Tam, Constantine S; O'Brien, Susan; Plunkett, William; Wierda, William; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim-Anh; Cortes, Jorge; Khouri, Issa; Kantarjian, Hagop; Lerner, Susan; Keating, Michael J

    2014-11-13

    Although fludarabine, cyclophosphamide, and rituximab (FCR) together are established as a standard first-line treatment of younger patients with chronic lymphocytic leukemia (CLL), there is little information to guide the management of patients with CLL refractory to, or who have relapsed after, receiving frontline FCR treatment. To define optimal salvage strategy and identify patients unsuitable for retreatment with FCR, we examined the survival and treatment outcome of 300 patients enrolled in a phase 2 study of FCR. After a median 142 months of follow-up, 156 patients developed progressive CLL, with a median survival of 51 months after disease progression. The duration of first remission (REM1) was a key determinant of survival after disease progression and first salvage. Patients with a short REM1 (<3 years) had a short survival period, irrespective of salvage therapy received; these patients have high unmet medical needs and are good candidates for investigation of novel therapies. In patients with a long REM1 (≥3 years), salvage treatment with either repeat FCR or lenalidomide-based therapy results in subsequent median survival exceeding 5 years; for these patients, FCR rechallenge represents a reasonable standard of care.

  4. Highly Diverse Efficacy of Salvage Treatment Regimens for Relapsed or Refractory Peripheral T-Cell Lymphoma: A Systematic Review

    PubMed Central

    Yang, Ya-Ting; Tai, Cheng-Jeng; Chen, Chiehfeng; Wu, Hong-Cheng; Mikhaylichenko, Natalia; Chiu, Hsien-Tsai; Chen, Yun-Yi; Hsu, Yi-Hsin Elsa

    2016-01-01

    Background The goal of this study was to perform a systematic review to examine the efficacy and safety of various salvage therapy regimens on patients with relapsed/refractory PTCL. Method The electronic searches were performed using PubMed, Cochrane Library, EMBASE, and Web of Science from inception through June 2015, with search terms related to relapsed/refractory PTCL, salvage chemotherapy regimens, and clinical trials. An eligible study met the following inclusion criteria: (1) Patients had refractory or relapsed PTCL; (2) drug regimens were used for salvage therapy; (3) the study was a clinical trial; (4) the study reported on a series of at least 10 patients of PTCL. Results Of 35 records identified, a total of 14 studies were eligible for systematic reviews, and 12 different salvage regimens were investigated. A total of 618 relapsed/refractory PTCL patients were identified. The ORRs ranged from 22% for those treated with lenalidomide to 86% for those with brentuximab vedotin. By the three most frequent subtypes, the ORRs ranged from 14.2% to 71.5% for patients with the PTCL-NOS subtype, 8% to 54% for AITL subtypes, and 24% to 86% for the ALCL subtype. The medians of DOR, PFS, and OS ranged from 2.5 to 16.6 months, 2.6 to 13.3 months, and 3.6 to 14.5 months, respectively. The most frequently reported grade 3 or 4 adverse events (AEs) were hematological AEs, such as neutropenia and thrombocytopenia. Conclusion The efficacy of salvage therapy regimens is highly diverse for patients with relapsed/refractory PTCL; this heterogeneity in therapeutic effects might be due to the diversity in mechanisms, PTCL subtype distribution, and/or numbers/profiles of prior therapy. Comparative studies with matched pair analysis are warranted for more evidence of the salvage treatment effect on relapsed or heavily pretreated patients with PTCL. PMID:27711130

  5. Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

    PubMed

    Brandes, Alba A; Tosoni, A; Franceschi, E; Blatt, V; Santoro, A; Faedi, M; Amistà, P; Gardiman, M; Labianca, R; Bianchini, C; Ermani, M; Reni, M

    2009-09-01

    Standardized salvage treatment has not yet proved effective in glioblastoma multiforme (GBM) patients who receive prior standard radiotherapy plus concomitant and adjuvant temozolomide. Patients with progressive GBM after radiotherapy plus concomitant and/or adjuvant temozolomide received three-weekly doses (100-75 mg m(2)) of fotemustine followed, after a 5-week rest, by fotemustine (100 mg m(2)) every 3 weeks for < or =1 year. Forty-three patients (29 M, 14 F; median age 51 years, range 34-68; median KPS 90) were enrolled. Progression-free survival at 6 months (PFS-6) was 20.9% (95% CI: 9-33%); three patients (7.1%) had partial response (PR); 15 (34.9%), disease stabilization (SD). The median survival was 6 months (95% CI: 5-7). MGMT promoter status was methylated in 8 (18.6%) and unmethylated in 26 (60.5%) and not assessable in 9 (20.9%) patients, respectively. Disease control was 75% versus 34.6% in methylated and unmethylated MGMT patients (P = 0.044); no significant difference was found between groups for PFS-6 and survival. Grade 3 and 4 thrombocytopenia and neutropenia were observed in 20.9 and 16.3% of patients, during the induction phase, and in 0 and 9.5% patients during the maintenance phase, respectively. The findings of the present trial, that evaluate fotemustine in a homogeneous population, may represent a new benchmark for nitrosourea activity. Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide.

  6. Prognostic impact of salvage treatment on hearing recovery in patients with sudden sensorineural hearing loss refractory to systemic corticosteroids: A retrospective observational study.

    PubMed

    Nakagawa, Takayuki; Yamamoto, Michio; Kumakawa, Kozo; Usami, Shin-Ichi; Hato, Naohito; Tabuchi, Keiji; Takahashi, Mariko; Fujiwara, Keizo; Sasaki, Akira; Komune, Shizuo; Yamamoto, Norio; Hiraumi, Harukazu; Sakamoto, Tatsunori; Shimizu, Akira; Ito, Juichi

    2016-10-01

    To determine the prognostic factors for hearing recovery in patients with sudden sensorineural hearing loss (SSHL) refractory to systemic corticosteroids following salvage treatment. This is a retrospective observational study at nine tertiary referral hospitals. A total of 120 patients with sudden deafness refractory to systemic corticosteroids were enrolled. The patients were randomly assigned to receive topical application of recombinant human IGF-1 or intratympanic injection of dexamethasone as salvage treatment. Multiple regression analysis was performed to identify determinants of hearing recovery using pure tone audiometry results at 8 weeks after treatment. Clinical predictors that were evaluated included age, sex, pretreatment hearing level, presence of vertiginous symptoms, days to study entry from symptom onset and salvage treatment assignment (IGF-1 vs. dexamethasone). The linear regression model identified age (P=0.001), pretreatment hearing level (P<0.001), days to study entry from symptom onset (P=0.011) and treatment assignment (P=0.033) at 8 weeks after treatment as significant variables influencing the recovery of pure tone audiometry average thresholds. Younger age (<60 years), early initiation of salvage treatment and treatment with topical IGF-1 therapy had significant effects on hearing recovery. The results indicate that early initiation and choice of treatment modalities for salvage treatment may be important for the prognosis of patients with refractory SSHL. The positive effect of topical IGF-1 therapy on hearing recovery indicates its utility as salvage treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Second Line of Defense Spares Program Assessment

    SciTech Connect

    Henderson, Dale L.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.

    2012-11-20

    The Office of the Second Line of Defense (SLD) is part of the Department of Energy‘s (DOE) National Nuclear Security Administration (NNSA). The SLD Program accomplishes its critical global security mission by forming cooperative relationships with partner countries to install passive radiation detection systems that augment traditional inspection and law enforcement measures by alerting border officials to the presence of special nuclear or other radiological materials in cross-border traffic. An important tenet of the program is to work collaboratively with these countries to establish the necessary processes, procedures, infrastructure and conditions that will enable them to fully assume the financial and technical responsibilities for operating the equipment. As the number of operational deployments grows, the SLD Program faces an increasingly complex logistics process to promote the timely and efficient supply of spare parts.

  8. Extracorporeal membrane oxygenation (ECMO) as salvage treatment for pulmonary Echinococcus granulosus infection with acute cyst rupture.

    PubMed

    Becker, Sören L; Fähndrich, Sebastian; Trudzinski, Franziska C; Gärtner, Barbara; Langer, Frank; Becker, Torben K; Bals, Robert; Lepper, Philipp M; Lensch, Christian

    2017-09-08

    Extracorporeal membrane oxygenation (ECMO) has been successfully used for the treatment of patients with respiratory failure due to severe infections. Though rare, parasites can also cause severe pulmonary disease. Tapeworms of the genus Echinococcus give rise to the development of cystic structures in the liver, lungs and other organs. Acute cyst rupture leads to potentially life-threatening infection, and affected patients may deteriorate rapidly. We describe the case of a young woman from Bulgaria who was admitted to hospital with severe dyspnoea, progressive chest pain and haemoptysis. Computed tomography of the chest was pathognomonic of cystic echinococcosis with acute cyst rupture. Following deterioration on mechanical ventilation, she was cannulated for veno-venous ECMO. The patient's condition improved considerably, and she could successfully be weaned from ECMO and mechanical ventilation. Following lobectomy of the affected left lower lobe, she was discharged home in good condition. This is the first report on the successful use of ECMO as salvage treatment for a severe manifestation of a helminthic disease. Due to recent migration to Western Europe, the number of patients presenting with respiratory failure due to pulmonary echinococcosis with cyst rupture is likely to increase. Copyright © 2017. Published by Elsevier Ltd.

  9. Metronomic chemotherapy and radiotherapy as salvage treatment in refractory or relapsed pediatric solid tumours

    PubMed Central

    Ali, A.M.; El-Sayed, M.I.

    2016-01-01

    Background Metronomic chemotherapy (mctx) combined with radiation therapy (rt) is an emerging anticancer strategy. The aim of the present study was to assess the efficacy of mctx combined with rt as salvage treatment in children with refractory or relapsed solid malignancies. Methods This prospective study enrolled patients with refractory or relapsed pediatric solid tumours from January 2013 to January 2015. Treatment consisted of 3–12 courses of mctx in all patients, followed by rt in patients who experienced local recurrence, distant metastases, or both. Each course of mctx consisted of oral celecoxib 100–400 mg twice daily (days 1–42), intravenous vinblastine 3 mg/m2 weekly (weeks 1–6), oral cyclophosphamide 2.5 mg/m2 daily (days 1–21), and oral methotrexate 15 mg/m2 twice weekly (days 21–42). Statistical methods used were the log-rank test and binary logistic regression. Results A favourable disease response (partial response or stable disease) was seen in 49 of 64 patients (76.6%), with mild acute toxicity occurring in 41 (64%). After a median follow-up of 14 months, 1-year overall survival was 62%. Pattern of disease relapse (p < 0.0001), time from initial treatment to relapse (p = 0.0002), and response to treatment (p < 0.0001) significantly affected survival. Age was the only factor that significantly correlated with treatment toxicity (p = 0.002; hazard ratio: 3.37; 95% confidence interval: 1.53 to 7.35) Conclusions Combining mctx with rt resulted in a favourable response rate, minimal toxicity, and 62% 1-year overall survival in patients with heavily pretreated recurrent disease. Patients with localized late recurrence or disease progression are the most likely to benefit from this regimen. PMID:27330362

  10. Salvage Treatment With Hypofractionated Radiotherapy in Patients With Recurrent Small Hepatocellular Carcinoma

    SciTech Connect

    Bae, Sun Hyun; Park, Hee Chul; Lim, Do Hoon; Lee, Jung Ae; Gwak, Geum Yeon; Choi, Moon Seok; Lee, Joon Hyoek; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2012-03-15

    Purpose: To investigate the rates of tumor response and local control in patients with recurrent small hepatocellular carcinoma (HCC) treated with hypofractionated radiotherapy (RT) as a salvage treatment and to evaluate treatment-related toxicities. Methods and Materials: Between 2006 and 2009, a total of 20 patients with recurrent small HCC were treated with hypofractionated RT after the failure of previous treatment. The eligibility criteria for hypofractionated RT were as follows: 1) HCC less than 5 cm, 2) HCC not adjacent to critical organs, 3) HCC without portal vein tumor thrombosis, and 4) less than 15% of normal liver volume that would be irradiated with 50% of prescribed dose. The RT dose was 50 Gy in 10 fractions. The tumor response was determined by CT scans performed 3 months after the end of RT. Results: The median follow-up period after RT was 22 months. The overall survival rates at 1 and 2 years were 100% and 87.9%, respectively. Complete response (CR) was achieved in seven of 20 lesions (35%) evaluated by CT scans performed 3 months after the end of RT. In-field local control was achieved in 85% of patients. Fourteen patients (70%) developed intra-hepatic metastases. Six patients developed grade 1 nausea or anorexia during RT, and two patients had progression of ascites after RT. There was no grade 3 or greater treatment-related toxicities. Conclusions: The current study showed a favorable outcome with respect to hypofractionated RT for small HCC. Partial liver irradiation with 50 Gy in 10 fractions is considered tolerable without severe complications.

  11. Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection.

    PubMed

    Kim, Jong Hun; Benefield, Russell J; Ditolla, Kali

    2016-11-01

    Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed-released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL(-1) ) compared to posaconazole SUS (median 1.0 μg mL(-1) ). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.

  12. Association of First-Line and Second-Line Antiretroviral Therapy Adherence

    PubMed Central

    Ramadhani, Habib O.; Bartlett, John A.; Thielman, Nathan M.; Pence, Brian W.; Kimani, Stephen M.; Maro, Venance P.; Mwako, Mtumwa S.; Masaki, Lazaro J.; Mmbando, Calvin E.; Minja, Mary G.; Lirhunde, Eileen S.; Miller, William C.

    2014-01-01

    Background  Adherence to first-line antiretroviral therapy (ART) may be an important indicator of adherence to second-line ART. Evaluating this relationship may be critical to identify patients at high risk for second-line failure, thereby exhausting their treatment options, and to intervene and improve patient outcomes. Methods  Adolescents and adults (n = 436) receiving second-line ART were administered standardized questionnaires that captured demographic characteristics and assessed adherence. Optimal and suboptimal cumulative adherence were defined as percentage adherence of ≥90% and <90%, respectively. Bivariable and multivariable binomial regression models were used to assess the prevalence of suboptimal adherence percentage by preswitch adherence status. Results  A total of 134 of 436 (30.7%) participants reported suboptimal adherence to second-line ART. Among 322 participants who had suboptimal adherence to first-line ART, 117 (36.3%) had suboptimal adherence to second-line ART compared with 17 of 114 (14.9%) who had optimal adherence to first-line ART. Participants who had suboptimal adherence to first-line ART were more likely to have suboptimal adherence to second-line ART (adjusted prevalence ratio, 2.4; 95% confidence interval, 1.5–3.9). Conclusions  Adherence to first-line ART is an important predictor of adherence to second-line ART. Targeted interventions should be evaluated in patients with suboptimal adherence before switching into second-line therapy to improve their outcomes. PMID:25734147

  13. Association of first-line and second-line antiretroviral therapy adherence.

    PubMed

    Ramadhani, Habib O; Bartlett, John A; Thielman, Nathan M; Pence, Brian W; Kimani, Stephen M; Maro, Venance P; Mwako, Mtumwa S; Masaki, Lazaro J; Mmbando, Calvin E; Minja, Mary G; Lirhunde, Eileen S; Miller, William C

    2014-09-01

    Adherence to first-line antiretroviral therapy (ART) may be an important indicator of adherence to second-line ART. Evaluating this relationship may be critical to identify patients at high risk for second-line failure, thereby exhausting their treatment options, and to intervene and improve patient outcomes. Adolescents and adults (n = 436) receiving second-line ART were administered standardized questionnaires that captured demographic characteristics and assessed adherence. Optimal and suboptimal cumulative adherence were defined as percentage adherence of ≥90% and <90%, respectively. Bivariable and multivariable binomial regression models were used to assess the prevalence of suboptimal adherence percentage by preswitch adherence status. A total of 134 of 436 (30.7%) participants reported suboptimal adherence to second-line ART. Among 322 participants who had suboptimal adherence to first-line ART, 117 (36.3%) had suboptimal adherence to second-line ART compared with 17 of 114 (14.9%) who had optimal adherence to first-line ART. Participants who had suboptimal adherence to first-line ART were more likely to have suboptimal adherence to second-line ART (adjusted prevalence ratio, 2.4; 95% confidence interval, 1.5-3.9). Adherence to first-line ART is an important predictor of adherence to second-line ART. Targeted interventions should be evaluated in patients with suboptimal adherence before switching into second-line therapy to improve their outcomes.

  14. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.

    PubMed

    Feng, Fei-Er; Feng, Ru; Wang, Min; Zhang, Jia-Min; Jiang, Hao; Jiang, Qian; Lu, Jin; Liu, Hui; Peng, Jun; Hou, Ming; Shen, Jian-Liang; Wang, Jing-Wen; Xu, Lan-Ping; Liu, Kai-Yan; Huang, Xiao-Jun; Zhang, Xiao-Hui

    2017-10-01

    Primary immune thrombocytopenia is a severe bleeding disorder. About 50-85% of patients achieve initial remission from first-line therapies, but optimal second-line treatment remains a challenge. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haemopoiesis, making it a possible treatment option. We aimed to evaluate the efficacy and safety of ATRA plus danazol versus danazol in non-splenectomised patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia. We did a multicentre, randomised, open-label, phase 2 study of adult patients (≥18 years) with primary immune thrombocytopenia from five different tertiary medical centres in China. Those eligible were non-splenectomised, resistant to corticosteroid treatment or relapsed, and had a platelet count less than 30 × 10(9) per L. Masked statisticians used simple randomisation to assign patients (1:1) to receive oral ATRA (10 mg twice daily) plus oral danazol (200 mg twice daily) or oral danazol monotherapy (200 mg twice daily) for 16 weeks. Neither clinicians nor patients were masked to group assignments. All patients were assessed every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. The primary endpoint was 12-month sustained response defined as platelet count of 30 × 10(9) per L or more and at least a doubling of baseline platelet count (partial response), or a platelet count of 100 × 10(9) per L or more (complete response) and the absence of bleeding without rescue medication at the 12-month follow-up. All randomly allocated patients, except for those who withdrew consent, were included in the modified intention-to-treat population and efficacy assessment, and all patients who received at least one dose of the study agents were included in the safety analysis. Study enrolment was stopped early because the trial results crossed the interim analysis efficacy boundary for sustained response. This trial is registered with Clinical

  15. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial.

    PubMed

    Soria, Jean-Charles; Felip, Enriqueta; Cobo, Manuel; Lu, Shun; Syrigos, Konstantinos; Lee, Ki Hyeong; Göker, Erdem; Georgoulias, Vassilis; Li, Wei; Isla, Dolores; Guclu, Salih Z; Morabito, Alessandro; Min, Young J; Ardizzoni, Andrea; Gadgeel, Shirish M; Wang, Bushi; Chand, Vikram K; Goss, Glenwood D

    2015-08-01

    There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1-10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9-2·9] vs 1·9 months [1·9-2·2]; hazard ratio [HR] 0·82 [95% CI 0·68-1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8-22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2-8·7] vs 6·8 months [5·9-7·8]; HR 0·81 [95% CI 0·69-0·95], p=0·0077), as were progression

  16. Second Line of Defense Spares Program

    SciTech Connect

    Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.

    2012-11-20

    During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.

  17. Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial.

    PubMed

    Zhu, Andrew X; Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Poon, Ronnie; Pastorelli, Davide; Blanc, Jean-Frederic; Chung, Hyun Cheol; Baron, Ari D; Pfiffer, Tulio Eduardo Flesch; Okusaka, Takuji; Kubackova, Katerina; Trojan, Jorg; Sastre, Javier; Chau, Ian; Chang, Shao-Chun; Abada, Paolo B; Yang, Ling; Schwartz, Jonathan D; Kudo, Masatoshi

    2015-07-01

    with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable. Eli Lilly and Co. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. How to find the Ariadne's thread in the labyrinth of salvage treatment options for metastatic colorectal cancer?

    PubMed

    Bronte, Giuseppe; Rolfo, Christian; Peeters, Marc; Russo, Antonio

    2014-06-01

    Since a chance for cure was found out in metastatic colorectal cancer (mCRC) patients undergoing a resection of liver and lung metastases, high tumor shrinkage by chemotherapy regimens and their combination with targeted agents have been addressed in potentially resectable mCRC. However, most mCRC patients cannot reach this opportunity because of tumor burden or metastatic sites. For these patients a salvage systemic therapy could be offered to prolong survival. To date, a huge number of clinical trials provided some evidences for the achievement of this goal. A lot of chemotherapeutic regimens in combination with biological therapies are now available. We tried to propose a simple way to choose the best options and to plan an optimal sequence of treatments. This tool could help the oncologists worldwide to better and easily manage mCRC patients who need salvage systemic therapy.

  19. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial.

    PubMed

    Machiels, Jean-Pascal H; Haddad, Robert I; Fayette, Jérôme; Licitra, Lisa F; Tahara, Makoto; Vermorken, Jan B; Clement, Paul M; Gauler, Thomas; Cupissol, Didier; Grau, Juan José; Guigay, Joël; Caponigro, Francesco; de Castro, Gilberto; de Souza Viana, Luciano; Keilholz, Ulrich; Del Campo, Joseph M; Cong, Xiuyu Julie; Ehrnrooth, Eva; Cohen, Ezra E W

    2015-05-01

    Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2:1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682. Between Jan 10, 2012, and

  20. Effectiveness of tipranavir versus darunavir as a salvage therapy in HIV-1 treatment-experienced patients.

    PubMed

    Domínguez-Hermosillo, Juan Carlos; Mata-Marin, José Antonio; Herrera-González, Norma Estela; Chávez-García, Marcelino; Huerta-García, Gloria; Nuñez-Rodríguez, Nohemí; García-Gámez, José Gerardo; Jiménez-Romero, Anai; Gaytán-Martínez, Jesús Enrique

    2016-09-30

    Although both tipranavir (TPV) and darunavir (DRV) represent important options for the management of patients with multi-protease inhibitor (PI)-resistant human immunodeficiency virus (HIV), currently there are no studies comparing the effectiveness and safety of these two drugs in the Mexican population. The aim of this study was to compare the effectiveness of TPV versus DRV as a salvage therapy in HIV-1 treatment-experienced patients. This was a comparative, prospective, cohort study. Patients with HIV and triple-class drug resistance evaluated at the Hospital de Infectología "La Raza", National Medical Center, were included. All patients had the protease and retrotranscriptase genotype; resistance mutation interpretation was done using the Stanford database. A total of 35 HIV-1 triple-class drug-resistant patients were analyzed. All of them received tenofovir and raltegravir, 22 received darunavir/ritonavir (DRV/r), and 13 received tipranavir/ritonavir (TPV/r) therapies. The median baseline RNA HIV-1 viral load and CD4+ cell count were 4.34 log (interquartile range [IQR], 4.15-4.72) and 267 cells/mm3 (IQR, 177-320) for the DRV/r group, and 4.14 log (IQR, 3.51-4.85) and 445 cells/mm3 (IQR, 252-558) for the TPV/r group. At week 24 of treatment, 91% of patients receiving DRV/r and 100% of patients receiving TPV/r had an RNA HIV-1 viral load < 50 copies/mL and a CD4+ cell count of 339 cells/mm3 (IQR, 252-447) and 556 cells/mm3 (IQR, 364-659), respectively. No significant difference was observed between DRV/r and TPV/r in terms of virological suppression in HIV-1 patients who were highly experienced in antiretroviral therapy.

  1. Temozolomide as salvage treatment for recurrent intracranial ependymomas of the adult: a retrospective study.

    PubMed

    Rudà, Roberta; Bosa, Chiara; Magistrello, Michela; Franchino, Federica; Pellerino, Alessia; Fiano, Valentina; Trevisan, Morena; Cassoni, Paola; Soffietti, Riccardo

    2016-02-01

    Few data are available on temozolomide (TMZ) in ependymomas.We investigated the response, survival, and correlation with MGMT promoter methylation in a cohort of patients with adult intracranial ependymoma receiving TMZ as salvage therapy after failure of surgery and radiotherapy. We retrieved clinical information from the institutional database and follow-up visits, and response to TMZ on MRI was evaluated according to the MacDonald criteria. Eighteen patients (median age, 42 y), with either WHO grade III (10) or grade II (8) ependymoma were evaluable. Tumor location at diagnosis was supratentorial in 11 patients and infratentorial in 7. Progression before TMZ was local in 11 patients, local and spinal in 6 patients, and spinal only in one patient. A median of 8 cycles of TMZ (1-24) was administered. Response to TMZ consisted of complete response (CR) in one (5%) patient, partial response (PR) in 3 (17%) patients, stable disease (SD) in 7 (39%) patients, and progressive disease (PD) in 7 (39%) patients. Maximum response occurred after 3, 10, 14, and 15 cycles, respectively, with neurological improvement in 2 patients. All 4 responding patients were chemotherapy naïve. Both anaplastic (2) and grade II (2) tumors responded. Median progression-free survival and overall survival were 9.69 months (95% CI, 3.22-30.98) and 30.55 months (95% CI, 12.85-52.17), respectively. MGMT methylation was available in 11 patients and was not correlated with response or outcome. TMZ has a role in recurrent chemo-naïve adult patients with intracranial ependymoma, regardless of tumor grade and MGMT methylation. We suggest that, after failure of surgery and radiotherapy, TMZ should be considered as a possible first-line treatment for recurrent ependymoma. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Temozolomide as salvage treatment for recurrent intracranial ependymomas of the adult: a retrospective study

    PubMed Central

    Rudà, Roberta; Bosa, Chiara; Magistrello, Michela; Franchino, Federica; Pellerino, Alessia; Fiano, Valentina; Trevisan, Morena; Cassoni, Paola; Soffietti, Riccardo

    2016-01-01

    Background Few data are available on temozolomide (TMZ) in ependymomas. We investigated the response, survival, and correlation with MGMT promoter methylation in a cohort of patients with adult intracranial ependymoma receiving TMZ as salvage therapy after failure of surgery and radiotherapy. Patients and Methods We retrieved clinical information from the institutional database and follow-up visits, and response to TMZ on MRI was evaluated according to the MacDonald criteria. Results Eighteen patients (median age, 42 y), with either WHO grade III (10) or grade II (8) ependymoma were evaluable. Tumor location at diagnosis was supratentorial in 11 patients and infratentorial in 7. Progression before TMZ was local in 11 patients, local and spinal in 6 patients, and spinal only in one patient. A median of 8 cycles of TMZ (1–24) was administered. Response to TMZ consisted of complete response (CR) in one (5%) patient, partial response (PR) in 3 (17%) patients, stable disease (SD) in 7 (39%) patients, and progressive disease (PD) in 7 (39%) patients. Maximum response occurred after 3, 10, 14, and 15 cycles, respectively, with neurological improvement in 2 patients. All 4 responding patients were chemotherapy naïve. Both anaplastic (2) and grade II (2) tumors responded. Median progression-free survival and overall survival were 9.69 months (95% CI, 3.22–30.98) and 30.55 months (95% CI, 12.85–52.17), respectively. MGMT methylation was available in 11 patients and was not correlated with response or outcome. Conclusion TMZ has a role in recurrent chemo-naïve adult patients with intracranial ependymoma, regardless of tumor grade and MGMT methylation. We suggest that, after failure of surgery and radiotherapy, TMZ should be considered as a possible first-line treatment for recurrent ependymoma. PMID:26323606

  3. Effect of post-fire salvage logging treatments on micobiological properties of two different soils in the Povince of Alicante.

    NASA Astrophysics Data System (ADS)

    Arcenegui, Victoria

    2017-04-01

    It is well known that the natural wildfire regime in Mediterranean forests is greatly disturbed by human activities. Fire can induce temporal or permanent changes in the soil (see Certini, 2005) and can retard or compromise the recovery of the ecosystem afterwards. Changes in soil properties and the impact on soil functions depend mainly on the severity of the fires (Neary et al., 1999) and type of soil and weather during and after burning (Robichaud & Hungerford, 2000). Post-fire management can have an additional impact on the ecosystem; in some cases, even more severe than the fire. Post-fire salvage logging treatments are very frequently but its ecological impact is uncertain. Mainly because there are so many variables at play. A research has been done in "Sierra de Mariola Natural Park" in Alcoi (M) and ''Cabo de San Antonio'' in Javea (J), both in the Province of Alicante (E Spain). A big forest fire (>500 has) occurred in July 2012 and in September 2014 respectively. After fire, salvage logging (SL) treatment were done. In the first area (M), with a soil classified as Typic Xerorthent, extraction of the burned wood using heavy machinery was applied. In contrast, in the second area (J), a Rhodoxeralf soil, not heavy machinery was used. Plots for monitoring this effect were installed in both areas and in a similar nearby area where no treatment was done, and then used as control (C) for comparison. Soil samplings were done immediately after treatment and 4 years and two years in M site and J site respectively. We examined the effect of salvage logging on basal soil respiration (BSR), and microbial biomass carbon (Cmic). Our results showed that in site M four years after the treatment, the plots without treatment showed a much better improvement for the properties monitored. And not differences were found in site J after two years of monitoring. The impact of salvage logging was different depending on the soil type and the way to do the treatment.

  4. CT-Guided 125I Seed Interstitial Brachytherapy as a Salvage Treatment for Recurrent Spinal Metastases after External Beam Radiotherapy

    PubMed Central

    Yao, Lihong; Cao, Qianqian; Yang, Jiwen; Meng, Na; Guo, Fuxin; Jiang, Yuliang; Tian, Suqing; Sun, Haitao

    2016-01-01

    The aim of this study is to evaluate the feasibility, safety, and clinical efficacy of CT-guided 125I seed interstitial brachytherapy in patients with recurrent spinal metastases after external beam radiotherapy (EBRT). Between August 2003 and September 2015, 26 spinal metastatic lesions (24 patients) were reirradiated by this salvage therapy modality. Treatment for all patients was preplanned using a three-dimensional treatment planning system 3–5 days before 125I seed interstitial brachytherapy; dosimetry verification was performed immediately after seed implantation. Median actual D90 was 99 Gy (range, 90–176), and spinal cord median Dmax was 39 Gy (range, 6–110). Median local control (LC) was 12 months (95% CI: 7.0–17.0). The 6- and 12-month LC rates were 52% and 40%, respectively. Median overall survival (OS) was 11 months (95% CI: 7.7–14.3); 6-month and 1-, 2-, and 3-year OS rates were 65%, 37%, 14%, and 9%, respectively. Pain-free survival ranged from 2 to 42 months (median, 6; 95% CI: 4.6–7.4). Treatment was well-tolerated, with no radiation-induced vertebral compression fractures or myelopathy reported. Reirradiation with CT-guided 125I seed interstitial brachytherapy appears to be feasible, safe, and effective as pain relief or salvage treatment for patients with recurrent spinal metastases after EBRT. PMID:28105434

  5. Predictive Factors for Second-Line Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Analysis

    PubMed Central

    Ivanyi, Philipp; Hornig, Mareike; Grünwald, Viktor

    2017-01-01

    Currently, about 50% of patients with metastatic renal cell carcinoma (mRCC) receive a second-line therapy. Therefore, the choice at each subsequent treatment line remains an important issue. In this retrospective study, we sought to identify pretreatment clinical parameters that could predict the likelihood of a patient receiving a second-line therapy. One hundred and sixty-one mRCC patients who received targeted therapy were evaluated. Descriptive statistics, Kaplan–Meier overall survival (OS), Cox regression, and binary logistic regression models were used for data analysis. Second-line therapy was given to 105 patients (65%). Patients with grade 1 tumor received second-line therapy more frequently than those with grade 2/3 tumors (P = 0.03). Only tumor grade was significantly different between patients receiving, or not receiving, second-line treatment. Median OS was significantly superior in patients receiving second-line therapy (32 versus 14 months; P = 0.007; hazard ratio [HR], 1.75; P = 0.008), patients with grade 1 tumors (130 versus 29 months in G2/3 tumors; HR, 3.85; P = 0.009), and in patients without early tumor progression (41 versus 11 months; HR, 5.04; 95% confidence interval [CI], 3.06–8.31; P < 0.001). In binary logistic regression, we identified early progression to be significantly associated with a higher probability of not receiving a second-line therapy (HR, 2.50; 95% CI, 1.01–6.21; P = 0.048). This study hypothesizes that pretreatment grade and early progression are predictive parameters for the selection of patients for second-line therapy. PMID:28405544

  6. Salvage esophagectomy

    PubMed Central

    2014-01-01

    Patients with locally advanced esophageal cancer are treated with definitive chemoradiation (dCXRT) for a number of reasons. Some patients are never referred to a surgeon for a con-versation about surgery, others decline surgery, and some are not candidates for surgery due to a sag in performance status secondary to therapy. Regardless of method of arrival at dCXRT, the risk of local/regional recurrence during follow-up is significant. Many of these patients are faced with limited options for therapy once dCXRT has failed. Salvage esoph-agectomy has historically been considered a morbid procedure and poor choice for lo-cal/regional recurrence. This chapter reviews the recent literature arguing the relevance of salvage resection. We recommend that any patient suffering from persistent or recurrent lo-cal/regional only disease after dCXRT should be referred to an experienced esophageal center to consider surgical options. PMID:24876940

  7. Salvage treatment of laparoscopic cholecystectomy-associated bile duct stenosis combining laparoscopic and endoscopic procedures: a case report.

    PubMed

    Iimuro, Yuji; Okada, Toshihiro; Ohashi, Koichiro; Uda, Yugo; Suzumura, Kazuhiro; Fujimoto, Jiro

    2013-11-01

    The incidence of laparoscopic cholecystectomy (LC)-associated bile duct injury has reached a steady state despite learning curve effect. Herein we report the case of a 74-year-old Japanese man who suffered from bile duct stenosis and stones after LC. The stenosis was due to stricture caused by surgical clips used inappropriately during LC. We planned a salvage treatment combining laparoscopic and endoscopic approaches. At laparoscopic observation, the clips had already invaded the right side of the bile duct; minimal absorbable suture was performed after all the clips were removed. The bile duct stenosis was then endoscopically dilated and the biliary stones were successfully removed. For the recurrent biliary stenosis after discharge, endoscopic balloon dilation was performed and multiple plastic stent tubes were placed. The stent tubes were removed 4 months later, and the patient has had no symptoms for 1 year. A combined laparoscopic and endoscopic approach was useful for the salvage treatment of LC-associated bile duct stenosis. © 2013 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Wiley Publishing Asia Pty Ltd.

  8. Clinical Outcomes of Castration-resistant Prostate Cancer Treatments Administered as Third or Fourth Line Following Failure of Docetaxel and Other Second-line Treatment: Results of an Italian Multicentre Study.

    PubMed

    Caffo, Orazio; De Giorgi, Ugo; Fratino, Lucia; Alesini, Daniele; Zagonel, Vittorina; Facchini, Gaetano; Gasparro, Donatello; Ortega, Cinzia; Tucci, Marcello; Verderame, Francesco; Campadelli, Enrico; Lo Re, Giovanni; Procopio, Giuseppe; Sabbatini, Roberto; Donini, Maddalena; Morelli, Franco; Sartori, Donata; Zucali, Paolo; Carrozza, Francesco; D'Angelo, Alessandro; Vicario, Giovanni; Massari, Francesco; Santini, Daniele; Sava, Teodoro; Messina, Caterina; Fornarini, Giuseppe; La Torre, Leonardo; Ricotta, Riccardo; Aieta, Michele; Mucciarini, Claudia; Zustovich, Fable; Macrini, Sveva; Burgio, Salvatore Luca; Santarossa, Sandra; D'Aniello, Carmine; Basso, Umberto; Tarasconi, Sara; Cortesi, Enrico; Buttigliero, Consuelo; Ruatta, Fiorella; Veccia, Antonello; Conteduca, Vincenza; Maines, Francesca; Galligioni, Enzo

    2015-07-01

    The availability of new agents (NAs) active in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel treatment (abiraterone acetate, cabazitaxel, and enzalutamide) has led to the possibility of using them sequentially to obtain a cumulative survival benefit. To provide clinical outcome data relating to a large cohort of mCRPC patients who received a third-line NA after the failure of docetaxel and another NA. We retrospectively reviewed the clinical records of patients who had received at least two successive NAs after the failure of docetaxel. The independent prognostic value of a series of pretreatment covariates on the primary outcome measure of overall survival was assessed using Cox regression analysis. We assessed 260 patients who received one third-line NA between January 2012 and December 2013, including 38 who received a further NA as fourth-line therapy. The median progression-free and overall survival from the start of third-line therapy was, respectively, 4 mo and 11 mo, with no significant differences between the NAs. Performance status, and haemoglobin and alkaline phosphatase levels were the only independent prognostic factors. The limitations of the study are mainly due its retrospective nature and the small number of patients treated with some of the sequences. We were unable to demonstrate a difference in the clinical outcomes of third-line NAs regardless of previous NA therapy. It is debated which sequence of treatments to adopt after docetaxel. Our data do not support the superiority of any of the three new agents in third-line treatment, regardless of the previously administered new agent. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  9. Rill erosion in burned and salvage logged western montane forests: Effects of logging equipment type, traffic level, and slash treatment

    NASA Astrophysics Data System (ADS)

    Wagenbrenner, J. W.; Robichaud, P. R.; Brown, R. E.

    2016-10-01

    Following wildfires, forest managers often consider salvage logging burned trees to recover monetary value of timber, reduce fuel loads, or to meet other objectives. Relatively little is known about the cumulative hydrologic effects of wildfire and subsequent timber harvest using logging equipment. We used controlled rill experiments in logged and unlogged (control) forests burned at high severity in northern Montana, eastern Washington, and southern British Columbia to quantify rill overland flow and sediment production rates (fluxes) after ground-based salvage logging. We tested different types of logging equipment-feller-bunchers, tracked and wheeled skidders, and wheeled forwarders-as well as traffic levels and the addition of slash to skid trails as a best management practice. Rill experiments were done at each location in the first year after the fire and repeated in subsequent years. Logging was completed in the first or second post-fire year. We found that ground-based logging using heavy equipment compacted soil, reduced soil water repellency, and reduced vegetation cover. Vegetation recovery rates were slower in most logged areas than the controls. Runoff rates were higher in the skidder and forwarder plots than their respective controls in the Montana and Washington sites in the year that logging occurred, and the difference in runoff between the skidder and control plots at the British Columbia site was nearly significant (p = 0.089). Most of the significant increases in runoff in the logged plots persisted for subsequent years. The type of skidder, the addition of slash, and the amount of forwarder traffic did not significantly affect the runoff rates. Across the three sites, rill sediment fluxes were 5-1900% greater in logged plots than the controls in the year of logging, and the increases were significant for all logging treatments except the low use forwarder trails. There was no difference in the first-year sediment fluxes between the feller

  10. Salvage treatment for childhood ependymoma after surgery only: Pitfalls of omitting 'at once' adjuvant treatment

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Giangaspero, Felice; Garre, Maria Luisa; Genitori, Lorenzo; Perilongo, Giorgio; Collini, Paola; Riva, Daria; Valentini, Laura; Scarzello, Giovanni; Poggi, Geraldina; Spreafico, Filippo; Peretta, Paola; Mascarin, Maurizio; Modena, Piergiorgio; Sozzi, Gabriella; Bedini, Nice; Biassoni, Veronica; Urgesi, Alessandro; Balestrini, Maria Rosa; Finocchiaro, Gaetano; Sandri, Alessandro; Gandola, Lorenza

    2006-08-01

    Purpose: To discuss the results obtained by giving adjuvant treatment for childhood ependymoma (EPD) at relapse after complete surgery only. Methods and Materials: Between 1993 and 2002, 63 children older than 3 years old entered the first Italian Association for Pediatric Hematology and Oncology protocol for EPD (group A), and another 14 patients were referred after relapsing after more tumor excisions only (group B). Prognostic factors were homogeneously matched in the two groups. We report on the outcome of group B. Results: Mean time to first local progression in group B had been 14 months. Tumors originated in the posterior fossa (PF) in 10 children and were supratentorial (ST) in 4; 11 had first been completely excised (NED) and 3 had residual disease (ED). Diagnoses were classic EPD in 9 patients, anaplastic in 5. Eight children were referred NED and 6 ED after two or more operations, 5 had cranial nerve palsy, 1 had recurrent meningitis, and 2 had persistent hydrocephalus. All received radiotherapy (RT) to tumor bed and 5 also had pre-RT chemotherapy. Six of 14 patients (6/10 with PF tumors) had a further relapse a mean 6 months after the last surgery; 4 of 6 died: progression-free survival and overall survival at 4 years after referral were 54.4% and 77%, respectively. Considering only PF tumors and setting time 0 as at the last surgery for group B, progression-free survival and overall survival were 32% and 50% for group B and 52% (p < 0.20)/70% (p < 0.29) for the 46 patients in group A with PF tumors. Local control was 32% in group B and 70.5% in group A (p = 0.02). Conclusions: Relapsers after surgery only, especially if with PF-EPD, do worse than those treated after first diagnosis; subsequent surgery for tumor relapse has severe neurologic sequelae.

  11. Second-line chemotherapy in relapsing or refractory patients with non-small cell lung cancer.

    PubMed

    Georgoulias, Vassilis A

    2002-12-01

    A comprehensive review of the literature on the efficacy of antitumor agents either alone or in combination as second-line chemotherapy in advanced non-small cell lung cancer (NSCLC) cancer was undertaken. An increasing number of patients with advanced NSCLC who progress or fail to respond to front-line chemotherapy are young and in good performance status, requiring further treatment. Since advanced NSCLC is an incurable and fatal disease, the aims of second-line chemotherapy should be the palliation of the symptoms and, probably, the improvement of survival. Docetaxel, gemcitabine, irinotecan and paclitaxel have shown a promising activity as second-line treatment in patients with NSCLC, and several phase II studies of regimens associating either these drugs or these drugs with CDDP and ifosfamide have shown objective responses ranging from 15 to 25% and a median survival ranging from 4 to 8 months. Two randomized trials have clearly demonstrated that single agent docetaxel in the second line setting confers a survival benefit and an improvement of both the quality of life and the control of tumor-related symptoms establishing, thus, the role of docetaxel as standard treatment for relapsing or refractory patients with NSCLC. Increasing evidence from both phase II and III studies seems to indicate that second-line chemotherapy may confer a survival benefit in a selected group of patients with advanced NSCLC. Copyright 2002 Elsevier Science Ireland Ltd.

  12. A Randomized Phase II Study to Assess the Efficacy of Pemetrexed or Sunitinib or Pemetrexed Plus Sunitinib in the Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer

    PubMed Central

    Heist, Rebecca S.; Wang, Xiaofei; Hodgson, Lydia; Otterson, Gregory A.; Stinchcombe, Thomas E.; Gandhi, Leena; Villalona-Calero, Miguel A.; Watson, Peter; Vokes, Everett E.; Socinski, Mark A.

    2014-01-01

    Background Second-line chemotherapy for advanced non-small cell lung cancer (NSCLC) improves survival modestly but new strategies are needed. This trial was designed to evaluate an antivascular endothelial growth factor strategy with or without standard chemotherapy in previously treated NSCLC. Methods Patients with stage IIIB/IV NSCLC with performance status 0 to 1 progressive after first-line chemotherapy were eligible for randomization to pemetrexed, sunitinib, or the combination. Patients were stratified by performance status, stage, and sex. Primary objective was 18-week progression-free survival (PFS) rate; secondary objectives included response, overall survival (OS), and toxicity. Target accrual was 225. The study was terminated early because of decreasing accrual rates. Results Between April 2008 and September 2011, 130 patients were registered and randomized; of this, 125 patients were treated. Baseline characteristics in the three arms were well balanced. Toxicity was higher in the sunitinib-containing arms. The 18-week PFS rate in the pemetrexed, sunitinib, and combination arms was 54% (95% confidence interval [CI], 40–71), 37% (95% CI, 25–54), and 48% (95% CI, 35–66), respectively (p= 0.25). Median PFS in the pemetrexed, sunitinib, and combination arms in months was 4.9 (2.1–8.8), 3.3 (2.3–4.2), and 3.7 (2.5–5.8), respectively (p= 0.18). There was an overall statistically significant difference in OS between the three arms: median OS in months was 10.5 (8.3–20.2) for pemetrexed, 8.0 (6.8–13.5) for sunitinib, and 6.7 (4.1–10.1) for the combination (p= 0.03). Conclusion Pemetrexed had a superior toxicity profile to either sunitinib or the combination of pemetrexed and sunitinib. The 18-week PFS rate was not significantly different between the arms. OS was significantly better with pemetrexed alone compared with the two sunitinib-containing arms, with the doublet performing worst for OS. PMID:24419419

  13. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection.

    PubMed

    Locke, J E; Magro, C M; Singer, A L; Segev, D L; Haas, M; Hillel, A T; King, K E; Kraus, E; Lees, L M; Melancon, J K; Stewart, Z A; Warren, D S; Zachary, A A; Montgomery, R A

    2009-01-01

    Desensitized patients are at high risk of developing acute antibody-mediated rejection (AMR). In most cases, the rejection episodes are mild and respond to a short course of plasmapheresis (PP) / low-dose IVIg treatment. However, a subset of patients experience severe AMR associated with sudden onset oliguria. We previously described the utility of emergent splenectomy in rescuing allografts in patients with this type of severe AMR. However, not all patients are good candidates for splenectomy. Here we present a single case in which eculizumab, a complement protein C5 antibody that inhibits the formation of the membrane attack complex (MAC), was used combined with PP/IVIg to salvage a kidney undergoing severe AMR. We show a marked decrease in C5b-C9 (MAC) complex deposition in the kidney after the administration of eculizumab.

  14. Bevacizumab plus chemotherapy versus chemotherapy alone as second-line treatment for patients with HER2-negative locally recurrent or metastatic breast cancer after first-line treatment with bevacizumab plus chemotherapy (TANIA): an open-label, randomised phase 3 trial.

    PubMed

    von Minckwitz, Gunter; Puglisi, Fabio; Cortes, Javier; Vrdoljak, Eduard; Marschner, Norbert; Zielinski, Christoph; Villanueva, Cristian; Romieu, Gilles; Lang, István; Ciruelos, Eva; De Laurentiis, Michele; Veyret, Corinne; de Ducla, Sabine; Freudensprung, Ulrich; Srock, Stefanie; Gligorov, Joseph

    2014-10-01

    Combining bevacizumab with first-line or second-line chemotherapy improves progression-free survival in HER2-negative locally recurrent or metastatic breast cancer. We assessed the efficacy and safety of further bevacizumab therapy in patients with locally recurrent or metastatic breast cancer whose disease had progressed after treatment with bevacizumab plus chemotherapy. In this open-label, randomised, phase 3 trial, we recruited patients who had HER2-negative locally recurrent or metastatic breast cancer that had progressed after receiving 12 weeks or more of first-line bevacizumab plus chemotherapy from 118 centres in 12 countries. Patients were randomly assigned (1:1) by use of a central interactive voice response system using a block randomisation schedule (block size four) stratified by hormone receptor status, first-line progression-free survival, selected chemotherapy, and lactate dehydrogenase concentration, to receive second-line single-agent chemotherapy either alone or with bevacizumab (15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks). Second-line therapy was continued until disease progression, unacceptable toxicity, or consent withdrawal. At progression, patients randomly assigned to chemotherapy alone received third-line chemotherapy without bevacizumab; those randomly assigned to bevacizumab continued bevacizumab with third-line chemotherapy. The primary endpoint was progression-free survival from randomisation to second-line progression or death in the intention-to-treat population. This trial is ongoing, and registered with ClinicalTrials.gov, number NCT01250379. Between Feb 17, 2011, and April 3, 2013, 494 patients were randomly assigned to treatment (247 in each group). The median duration of follow-up at the time of this prespecified primary progression-free survival analysis was 15·9 months (IQR 9·1-21·7) in the chemotherapy-alone group and 16·1 months (10·6-22·7) in the combination group. Progression-free survival was significantly

  15. Tenofovir or zidovudine in second-line antiretroviral therapy after stavudine failure in southern Africa.

    PubMed

    Wandeler, Gilles; Gerber, Florian; Rohr, Julia; Chi, Benjamin H; Orrell, Catherine; Chimbetete, Cleophas; Prozesky, Hans; Boulle, Andrew; Hoffmann, Christopher J; Gsponer, Thomas; Fox, Matthew P; Zwahlen, Marcel; Egger, Matthias

    2014-01-01

    There is debate over using tenofovir or zidovudine alongside lamivudine in second-line antiretroviral therapy (ART) following stavudine failure. We analysed outcomes in cohorts from South Africa, Zambia and Zimbabwe Patients aged ≥16 years who switched from a first-line regimen including stavudine to a ritonavir-boosted lopinavir-based second-line regimen with lamivudine or emtricitabine and zidovudine or tenofovir in seven ART programmes in southern Africa were included. We estimated the causal effect of receiving tenofovir or zidovudine on mortality and virological failure using Cox proportional hazards marginal structural models. Its parameters were estimated using inverse probability of treatment weights. Baseline characteristics were age, sex, calendar year and country. CD4(+) T-cell count, creatinine and haemoglobin levels were included as time-dependent confounders. A total of 1,256 patients on second-line ART, including 958 on tenofovir, were analysed. Patients on tenofovir were more likely to have switched to second-line ART in recent years, spent more time on first-line ART (33 versus 24 months) and had lower CD4(+) T-cell counts (172 versus 341 cells/μl) at initiation of second-line ART. The adjusted hazard ratio comparing tenofovir with zidovudine was 1.00 (95% CI 0.59, 1.68) for virological failure and 1.40 (0.57, 3.41) for death. We did not find any difference in treatment outcomes between patients on tenofovir or zidovudine; however, the precision of our estimates was limited. There is an urgent need for randomized trials to inform second-line ART strategies in resource-limited settings.

  16. Re-Evaluating Progression in an Era of Progress: A Review of First- and Second-Line Treatment Options in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer

    PubMed Central

    Castellanos, Emily H.

    2016-01-01

    The advent of crizotinib, the first small molecule inhibitor against anaplastic lymphoma kinase (ALK), has led to impressive advances in the care of patients with advanced ALK-rearranged non-small cell lung cancer. The development of second-generation ALK inhibitors, starting with the recent U.S. Food and Drug Administration approval of ceritinib, promises to expand the therapeutic landscape for this cohort of patients. With increasing use of molecularly targeted therapy options, it has been observed that disease progression in patients receiving targeted agents has a heterogeneous biology, manifesting as either oligoprogressive or widely progressive disease, which may require development of innovative treatment strategies. This review discusses the first- and second-generation ALK inhibitors approved or in clinical development, as well as the novel challenges and approaches to disease progression in patients on targeted agents. Implications for Practice: The identification of driver mutations in non-small cell lung cancer (NSCLC), most prominently epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), has expanded treatment options for a significant cohort of patients. However, the success of targeted agents has brought new challenges, particularly regarding management of progression. Progression manifests heterogeneously, and management of oligoprogression may differ from diffusely progressive disease. Multiple options for treatment at progression exist, and it is becoming evident that selecting the best avenue of care requires understanding the biology and potential drivers of disease progression. This review discusses the array of treatment options available for patients with ALK-positive NSCLC, as well as evaluation and treatment of progressive disease. PMID:27053502

  17. Salvage Treatment for Recurrent Intracranial Germinoma After Reduced-Volume Radiotherapy: A Single-Institution Experience and Review of the Literature

    SciTech Connect

    Hu, Yu-Wen; Huang, Pin-I; Wong, Tai-Tong; Ho, Donald Ming-Tak; Chang, Kai-Ping; Guo, Wan-Yuo; Chang, Feng-Chi; Shiau, Cheng-Yin; Liang, Muh-Lii; Lee, Yi-Yen; and others

    2012-11-01

    Purpose: Intracranial germinomas (IGs) are highly curable with radiotherapy (RT). However, recurrence still occurs, especially when limited-field RT is applied, and the optimal salvage therapy remains controversial. Methods and Materials: Between January 1989 and December 2010, 14 patients with clinically or pathologically diagnosed recurrent IGs after RT were reviewed at our institution. Of these, 11 received focal-field RT, and the other 3 received whole-brain irradiation, whole-ventricle irradiation, and Gamma Knife radiosurgery as the respective first course of RT. In addition, we identified from the literature 88 patients with recurrent IGs after reduced-volume RT, in whom the details of salvage therapy were recorded. Results: The median time to recurrence was 30.3 months (range, 3.8-134.9 months). One patient did not receive further treatment and was lost during follow-up. Of the patients, 7 underwent salvage with craniospinal irradiation (CSI) plus chemotherapy (CT), 4 with CSI alone, 1 with whole-brain irradiation plus CT, and 1 with Gamma Knife radiosurgery. The median follow-up time was 105.1 months (range, 24.2-180.9 months). Three patients died without evidence of disease progression: two from second malignancies and one from unknown cause. The others remained disease free. The 3-year survival rate after recurrence was 83.3%. A total of 102 patients from our study and the literature review were analyzed to determine the factors affecting prognosis and outcomes. After recurrence, the 5-year survival rates were 71% and 92.9% for all patients and for those receiving salvage CSI, respectively. Univariate analysis showed that initial RT volume, initial RT dose, initial CT, and salvage RT type were significant prognostic predictors of survival. On multivariable analysis, salvage CSI was the most significant factor (p = 0.03). Conclusions: Protracted follow-up is recommended because late recurrence is not uncommon. CSI with or without CT is an effective

  18. Glufosfamide administered by 1-hour infusion as a second-line treatment for advanced non-small cell lung cancer; a phase II trial of the EORTC-New Drug Development Group.

    PubMed

    Giaccone, G; Smit, E F; de Jonge, M; Dansin, E; Briasoulis, E; Ardizzoni, A; Douillard, J-Y; Spaeth, D; Lacombe, D; Baron, B; Bachmann, P; Fumoleau, P

    2004-03-01

    The activity of glufosfamide (beta-D-glucosylisophosphoramide mustard) was tested in a multicentre phase II clinical trial in patients with advanced non-small cell lung cancer (NSCLC) who had received one prior line of platinum-based chemotherapy. Patients were treated with 5000 mg/m(2) glufosfamide by a 1-h intravenous (i.v.) infusion every 3 weeks following registration at the European Organisation for Research and Treatment of Cancer (EORTC) Data Center. Patients were randomised between hydration and no hydration to evaluate the nephroprotective effects of forced diuresis. Patients experiencing >/= 35 micromol/l increase of serum creatinine compared with baseline values were taken off the treatment. The Response evaluation criteria in solid tumours (RECIST) criteria were applied for the response assessment. Blood sampling was performed for a pharmacokinetic analysis. 39 patients from seven institutions were registered and a median of three cycles was given (range 0-6) cycles; 20 patients were randomised to the hydration arm. Haematological toxicity was mild, but treatment-related metabolic and electrolytic abnormalities and increases of serum creatinine occurred in several patients. Hydration did not have any significant influence on the plasma pharmacokinetics of glufosfamide and did not show any nephroprotective effect. Only one confirmed partial remission was observed (response rate 3%; 95% (Confidence Interval (CI) 0-14) and 18 cases with stable disease (49%) were recorded as assessed by an independent panel. Median survival of all patients treated was 5.8 months (95% CI 4.2-7.9). In conclusion, glufosfamide administered by a 1-h infusion every 3 weeks has modest activity in advanced NSCLC patients after one prior platinum-based chemotherapy.

  19. Effectiveness and tolerability of second-line treatment with vildagliptin versus other oral drugs for type 2 diabetes in a real-world setting in the Middle East: results from the EDGE study

    PubMed Central

    Saab, Charles; Al-Saber, Feryal A; Haddad, Jihad; Jallo, Mahir Khalil; Steitieh, Habib; Bader, Giovanni; Ibrahim, Mohamed

    2015-01-01

    Background Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that requires treatment intensification with antihyperglycemic agents due to progressive deterioration of β-cell function. A large observational study of 45,868 patients with T2DM across 27 countries (EDGE) assessed the effectiveness and safety of vildagliptin as add-on to other oral antidiabetic drugs (OADs) versus other comparator OAD combinations. Here, we present results from the Middle East countries (Bahrain, Jordan, Kuwait, Lebanon, Oman, Palestine, and the United Arab Emirates). Methods Patients inadequately controlled with OAD monotherapy were eligible after the add-on treatment was chosen by the physician based on clinical judgment and patient need. Patients were assigned to either vildagliptin or comparator OADs (sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, or metformin, except incretin-based therapies) based on the add-on therapy. The primary endpoint was the proportion of patients achieving a glycated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event, or weight gain ≥5%. One of the secondary endpoints was the proportion of patients achieving HbA1c <7% without hypoglycemia or weight gain. Change in HbA1c from baseline to study endpoint and safety were also assessed. Results Of the 4,780 patients enrolled in the Middle East, 2,513 received vildagliptin and 2,267 received other OADs. Overall, the mean (± standard deviation) age at baseline was 52.1±10.2 years, mean HbA1c was 8.5%±1.3%, and mean T2DM duration was 4.2±4.0 years. The proportion of patients achieving the primary (76.1% versus 61.6%, P<0.0001) and secondary (54.8% versus 29.9%, P<0.0001) endpoints was higher with vildagliptin than with the comparator OADs. The unadjusted odds ratios for the primary and secondary endpoints were 1.98 (95% confidence interval 1.75–2.25) and 2.8 (95% confidence interval 2.5–3

  20. Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib: Patient-focused outcome results from the randomised phase III REACH study.

    PubMed

    Chau, Ian; Peck-Radosavljevic, Markus; Borg, Christophe; Malfertheiner, Peter; Seitz, Jean Francois; Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Kudo, Masatoshi; Poon, Ronnie; Pastorelli, Davide; Blanc, Jean-Frederic; Chung, Hyun Cheol; Baron, Ari D; Okusaka, Takuji; Bowman, L; Cui, Zhanglin Lin; Girvan, Allicia C; Abada, Paolo B; Yang, Ling; Zhu, Andrew X

    2017-08-01

    To report patient-focused outcomes as measured by quality of life (QoL) and performance status (PS) in REACH, a phase III placebo-controlled randomised study, assessing ramucirumab in advanced hepatocellular carcinoma (HCC) patients who received prior sorafenib. Eligible patients had advanced HCC, Child-Pugh A, PS 0 or 1 and prior sorafenib. Patients received ramucirumab (8 mg/kg) or placebo (1:1) on day 1 of a 2-week cycle. QoL was assessed by FACT Hepatobiliary Symptom Index (FHSI)-8 and EuroQoL (EQ-5D) at baseline; cycles 4, 10, and 16; and end of treatment. PS was assessed at baseline, each cycle, and end of treatment. Deterioration in FHSI-8 was defined as a ≥3-point decrease from baseline and PS deterioration was defined as a change of ≥2. Both intention-to-treat and pre-specified subgroup of patients with baseline serum alpha-fetoprotein (AFP) ≥400 ng/mL were assessed. There were 565 patients randomised to ramucirumab and placebo. Compliance with FHSI and EQ-5D was high and similar between groups. In the ITT population, deterioration in FHSI-8, EQ-5D, and PS was similar between ramucirumab and placebo. In patients with baseline AFP ≥400 ng/mL, ramucirumab significantly reduced deterioration in FHSI-8 at the end of treatment compared with placebo (P = 0.0381), and there was a trend towards a delay in the deterioration of symptoms in FHSI-8 (HR 0.690; P = 0.054) and PS (HR 0.642; P = 0.057) in favour of ramucirumab. We report one of the most comprehensive data sets of QoL and symptom burden in patients undergoing systemic therapy for advanced HCC. Ramucirumab was associated with no worsening of QoL. In patients with baseline AFP ≥400 ng/mL, the significant survival benefit observed in patients treated with ramucirumab was coupled with a trend in patient-focused outcome benefits. NCT01140347. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. NNSA B-Roll: Second Line of Defense

    SciTech Connect

    2010-05-21

    The NNSA Office of Second Line of Defense (SLD) works to prevent illicit trafficking in nuclear and radiological materials by securing international land borders, seaports and airports that may be used as smuggling routes for materials needed for a nuclear device or a radiological dispersal device.

  2. Exeresis and Brachytherapy as Salvage Treatment for Local Recurrence After Conservative Treatment for Breast Cancer: Results of a Ten-Year Pilot Study

    SciTech Connect

    Guix, Benjamin; Lejarcegui, Jose Antonio; Tello, Jose Ignacio; Zanon, Gabriel; Henriquez, Ivan; Finestres, Fernando; Martinez, Antonio; Fernandez-Ibiza, Jaume; Quinzanos, Luis; Palombo, Pau; Encinas, Xavier; Guix, Ines

    2010-11-01

    Purpose: To analyze the long-term results of a pilot study assessing excision and brachytherapy as salvage treatment for local recurrence after conservative treatment of breast cancer. Methods and Materials: Between December 1990 and March 2001, 36 patients with breast-only recurrence less than 3 cm in diameter after conservative treatment for Stage I or II breast carcinoma were treated with local excision followed by high-dose rate brachytherapy implants (30 Gy in 12 fractions over a period of 5 days). No patient was lost to follow-up. Special attention was paid to local, regional, or distant recurrences; survival; cosmesis; and early and late side effects. Results: All patients completed treatment. During follow-up (range, 1-13 years), 8 patients presented metastases (2 regional and 6 distant) as their first site of failure, 1 had a differed local recurrence, and 1 died of the disease. Actuarial results at 10 years were as follows: local control, 89.4%; disease-free survival, 64.4%; and survival, 96.7%. Cosmetic results were satisfactory in 90.4%. No patient had Grade 3 or 4 early or late complications. Of the 11 patients followed up for at least 10 years, all but 1 still had their breast in place at the 10-year stage. Conclusions: High-dose rate brachytherapy is a safe, effective treatment for small-size, low-risk local recurrence after local excision in conservatively treated patients. The dose of 30 Gy of high-dose rate brachytherapy (12 fractions over a period of 5 days twice daily) was well tolerated. The excellent results support the use of breast preservation as salvage treatment in selected patients with local recurrence after conservative treatment for breast cancer.

  3. Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer

    PubMed Central

    2013-01-01

    Introduction This Phase I study evaluated the safety, tolerability and efficacy of olaparib, a potent oral poly(ADP-ribose) polymerase (PARP) inhibitor, in combination with paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). Methods Eligible patients who had received ≤1 prior cytotoxic regimen for mTNBC were treated with olaparib 200 mg bid continuously plus weekly paclitaxel 90 mg/m2 for three weeks per four-week cycle. Dose modifications in a large proportion of patients due to neutropenia resulted in enrollment of a second cohort of patients who, if they experienced grade ≥2 neutropenia in cycle 1, received granulocyte-colony stimulating factor, which was continued prophylactically in subsequent cycles. All patients had measurable disease; tumor responses were evaluated according to RECIST (version 1.0). Results Nineteen patients (cohort 1, n = 9; cohort 2, n = 10) received treatment; 15 had received prior taxane chemotherapy. The most frequent adverse events were diarrhea (n = 12, 63%), nausea (n = 11, 58%) and neutropenia (n = 11, 58%). Seven neutropenia events were reported in cohort 1 (four grade ≥3) and four in cohort 2 (two grade ≥3, including one event of febrile neutropenia). The median (range) dose intensity of paclitaxel was 57% (26 to 100%) in cohort 1 and 73% (29 to 100%) in cohort 2. Seven patients (37%) had a confirmed partial response; one patient remains on olaparib monotherapy without progression. Conclusions The combination of olaparib and weekly paclitaxel was complicated by a significant clinical interaction, with higher-than-expected rates of neutropenia despite secondary prophylaxis. Given the encouraging response rate, alternative scheduling and dosing strategies should be considered (funded by AstraZeneca; ClinicalTrials.gov, NCT00707707). PMID:24063698

  4. Serum anti-Mullerian hormone levels after ovarian drilling for the second-line treatment of polycystic ovary syndrome: a pilot-randomized study comparing laparoscopy and transvaginal hydrolaparoscopy.

    PubMed

    Giampaolino, Pierluigi; Morra, Ilaria; Della Corte, Luigi; Sparice, Stefania; Di Carlo, Costantino; Nappi, Carmine; Bifulco, Giuseppe

    2017-01-01

    Aim of the study was to asses and compare serum anti-Mullerian harmone (AMH) levels after laparoscopic ovarian drilling (LOD) and transvaginal hydrolaparoscopy (THL) ovarian drilling in clomifene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients; secondary outcome was to evaluate postoperative pain to estimate the acceptability of procedures. A total of 246 patients with CC-resistant PCOS were randomized into two groups: 123 underwent LOD and 123 underwent THL ovarian drilling. AMH serum levels were evaluated before and after the procedure; moreover, women were asked to rate pain on a visual analog scale (VAS) from 0 (no pain, perfectly acceptable) to 10 (unbearable pain, completely unacceptable). In both groups, postoperative serum AMH levels were significantly reduced compared to preoperative levels (6.06 ± 1.18 and 5.84 ± 1.16 versus 5.00 ± 1.29 and 4.83 ± 1.10; p < 0.0001). Comparing postoperative serum AMH levels, no statistically significant difference was observed between the two surgical technique. After the procedure, mean pain VAS score was significantly higher for women who underwent LOD ovarian drilling in comparison to THL (3.26 ± 1.1 versus 1.11 ± 0.5; p < 0.0001). In conclusion, THL ovarian drilling is comparable to the LOD in terms of reduction in AMH, but it is preferred by patients in terms of acceptability. These results could support to use of THL ovarian drilling in the treatment of patients with CC- resistant PCOS.

  5. Clinical outcomes of gamma knife radiosurgery in the salvage treatment of patients with recurrent high-grade glioma.

    PubMed

    Elaimy, Ameer L; Mackay, Alexander R; Lamoreaux, Wayne T; Demakas, John J; Fairbanks, Robert K; Cooke, Barton S; Lamm, Andrew F; Lee, Christopher M

    2013-12-01

    Previously published randomized evidence did not report a survival advantage for patients diagnosed with grade IV glioma who were treated with stereotactic radiosurgery followed by external beam radiation therapy and chemotherapy when compared to patients treated with external beam radiation therapy and chemotherapy alone. In recent years, gamma knife radiosurgery has become increasingly popular as a salvage treatment modality for patients diagnosed with recurrent high-grade glioma. The purpose of this article is to review the efficacy of gamma knife radiosurgery for patients who suffer from this malignancy. Retrospective, prospective, and randomized clinical studies published between the years 2000 and 2012 analyzing gamma knife radiosurgery for patients with high-grade glioma were reviewed. After assessing patient age, Karnofsky performance status, tumor histology, and extent of resection, gamma knife radiosurgery is a viable, minimally invasive treatment option for patients diagnosed with recurrent high-grade glioma. The available prospective and retrospective evidence suggests that gamma knife radiosurgery provides patients with a high local tumor control rate and a median survival after tumor recurrence ranging from 13 to 26 months. Gamma knife radiosurgery followed by chemotherapy for recurrent high-grade glioma may provide select patients with increased levels of survival. However, further investigation into this matter is needed due to the limited number of published reports. Additional clinical research is also needed to analyze the efficacy and radiation-related toxicities of fractionated gamma knife radiosurgery due to its potential to limit treatment-associated morbidity. Gamma knife radiosurgery is a safe and effective treatment option for select patients diagnosed with recurrent high-grade glioma. Although treatment outcomes have improved, further evidence in the form of phase III randomized trials is needed to assess the durability of treating

  6. Second-Line Chemotherapy of Advanced Colorectal Cancer: Predictive and Prognostic Factors.

    PubMed

    Forgacz, Krzysztof; Agrawal, Anil K; Sawicki, Tomasz; Marek, Grzegorz W

    2016-01-01

    Colorectal cancer progression presents a significant clinical problem. After its dissemination, the foundation of its treatment comprises of palliative chemotherapy. The aim of this study was to assess the predictive and prognostic value of clinical response to second line treatment (with capecitabine or with a two-drug regimen including irinotecan) and to analyze its relation to selected clinical and pathological variables with respect to time to disease progression. The retrospective analysis of 164 patients with advanced colorectal cancer treated in 2001- -2008 included chosen clinical, pathological and follow-up data. Response to second-line chemotherapy was observed in 34 out of 164 patients: In 18/82 in the irinotecan group (22%) and in 16/82 in the capecitabine group (19.5%). The mean survival time to progression following the second line of treatment amounted to 5.85 and 6.2 months respectively. Statistically, a higher number of patients in good condition of 0 to 1 was documented in the group responding to treatment. Significant correlation was documented between primary stage of the disease and time to progression in patients treated with capecitabine (p = 0.0258). The recurrence of the disease was observed in 44/45 patients following operation with radical intention but with an insufficient number of excised lymph nodes. A significantly longer time to progression was observed in women treated with capecitabine. In logistic regression, lack of treatment response was found to be an independent factor affecting the time to disease progression. Patients who did not respond to the second line of treatment demonstrated a significantly shorter time to disease progression than patients who responded to it and they showed a significantly higher number of patients with leucopenia during treatment. Clinical response to treatment in both treated groups is of significant importance for the probability of local recurrence of the disease, preservation of a good patient

  7. Second-line failure and first experience with third-line antiretroviral therapy in Mumbai, India

    PubMed Central

    Khan, Samsuddin; Das, Mrinalini; Andries, Aristomo; Deshpande, Alaka; Mansoor, Homa; Saranchuk, Peter; Isaakidis, Petros

    2014-01-01

    Background There are limited data on the failure of second-line antiretroviral therapy (ART) and the use of third-line ART in people living with HIV in resource-limited settings. Since 2011, the Médecins Sans Frontières (MSF) HIV/tuberculosis programme in Mumbai, India, has been providing third-line ART to patients in care. Objective To describe the experiences and programmatic challenges during management of suspected second-line ART failure and third-line ART therapy for patients living with HIV, including the use of HIV viral load (VL) testing. Design This was a retrospective, observational cohort study of patients with suspected second-line ART treatment failure, who were followed for at least 12 months between January 2011 and March 2014. Results A total of 47 patients with suspected second-line failure met the inclusion criteria during the study period. Twenty-nine of them (62%) responded to enhanced adherence support, had a subsequent undetectable VL after a median duration of 3 months and remained on second-line ART. The other 18 patients had to be initiated on a third-line ART regimen, which consisted of darunavir–ritonavir, raltegravir, and one or more appropriate nucleoside or nucleotide reverse transcriptase inhibitors, based on the results of HIV genotype testing. Of the 13 patients for whom follow-up VL results were available, 11 achieved virological suppression after a median duration of 3 months on third-line ART (interquartile range: 2.5–3.0). No serious treatment-related adverse events were recorded. Conclusions With intensive counselling and adherence support in those suspected of failing second-line ART, unnecessary switching to more expensive third-line ART can be averted in the majority of cases. However, there is an increasing need for access to third-line ART medications such as darunavir and raltegravir, for which national ART programmes should be prepared. The cost of such medications and inadequate access to VL monitoring and HIV

  8. Timber salvage economics

    Treesearch

    Jeffrey P. Prestemon; Thomas P. Holmes

    2008-01-01

    Timber salvage is commonly done following natural disturbances, to recover some value from damaged forests. Decision making about salvage, however, is affected by ownership objectives, the nature of the damage agent, site factors, and the strength of the local timber market. For profit-maximizing landowners, salvage decisions must balance the cost of harvesting...

  9. Effect of combined treatment with salvage radiotherapy plus androgen suppression on quality of life in patients with recurrent prostate cancer after radical prostatectomy

    SciTech Connect

    Pearce, Andrew; Choo, Richard . E-mail: choo.c@mayo.edu; Danjoux, Cyril; Morton, Gerard; Loblaw, D. Andrew; Szumacher, Ewa; Cheung, Patrick; Deboer, Gerrit; Chander, Sarat

    2006-05-01

    Purpose: To examine the effect of salvage radiotherapy (RT) plus 2-year androgen suppression (AS) on quality of life (QOL). Methods and Materials: A total of 74 patients with biopsy-proven local recurrence or PSA relapse after radical prostatectomy were treated with salvage RT plus 2-year AS, as per a phase II study. Quality of life was prospectively assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-Item Version 3.0 with the added prostate cancer-specific module at baseline and predefined follow-up visits. Results: Patients experienced a significant increase in bowel dysfunction (23%) by the end of RT (p < 0.0001). This bowel dysfunction improved after RT but remained slightly elevated (5-10%) throughout the 2-year AS period. This extent of residual bowel dysfunction would be considered of minimal clinical importance. A similar, but less pronounced, pattern of change did occur for urinary dysfunction. Erectile function showed no change during RT, but had an abrupt decline (10%) with initiation of AS that was of moderate clinical significance (p < 0.01). None of the other QOL domains demonstrated a persistent, significant change from baseline that would be considered of major clinical significance. Conclusion: The combined treatment with salvage RT plus 2-year AS had relatively minor long-term effects on QOL.

  10. Historical Evolution of Second-Line Therapy in Non-Small Cell Lung Cancer

    PubMed Central

    Lazzari, Chiara; Bulotta, Alessandra; Ducceschi, Monika; Viganò, Maria Grazia; Brioschi, Elena; Corti, Francesca; Gianni, Luca; Gregorc, Vanesa

    2017-01-01

    Innovative therapeutic agents have significantly improved outcome with an acceptable safety profile in a substantial proportion of non-small cell lung cancer (NSCLC) patients, who depend on oncogenic molecular alterations for their malignant phenotype. Despite the survival improvement achieved with first-line chemotherapy, about 30% of patients do not obtain a tumor response. Moreover, those patients, initially sensitive to treatment, acquire resistance and develop tumor progression after a median of about 5 months. Approximately 60% of the patients progressing from first-line chemotherapy receive further systemic treatment in the second-line setting. Moreover, new options have emerged in the second-line armamentarium for the treatment of patients with NSCLC, including immune checkpoint inhibitors and antiangiogenic agents. The current review provides an overview on the clinical studies that gained the approval of chemotherapy agents (docetaxel and pemetrexed) and epidermal growth factor receptor gene–tyrosine kinase inhibitors as second-line treatment options for NSCLC patients, not carrying molecular alterations. PMID:28168189

  11. Vaginal Recurrence More than 17 Years after Hysterectomy and Adjuvant Treatment for Uterine Carcinoma with Successful Salvage Brachytherapy: A Case Report

    PubMed Central

    Yechieli, Raphael; Robbins, Jared R.; Schultz, Daniel; Munkarah, Adnan; Elshaikh, Mohamed A.

    2011-01-01

    Purpose Although the majority of recurrences occur within the first 3 years of hysterectomy for endometrioid carcinoma, we report herein a successful salvage vaginal brachytherapy in a patient with endometrioid uterine carcinoma which recurred more than 17 years after initial treatment. Materials and Methods A 61-year-old female was diagnosed with endometrioid adenocarcinoma of the uterus and treated with TAH-BSO, followed by adjuvant external beam radiation therapy (EBRT) to the whole pelvis. After remaining free of any recurrent or metastatic disease for more than 17 years, she was diagnosed with isolated vaginal cuff recurrence and successfully treated with a salvage high-dose-rate intracavitary vaginal brachytherapy. Results The patient remained disease free until her death from unrelated causes 7 years later. Conclusion To the best of our knowledge, this case represents the longest time to recurrence of endometrial cancer in someone who had been treated with TAH-BSO and adjuvant pelvic EBRT. This case highlights that even with adjuvant therapy, late recurrences may occur, and successful salvage brachytherapy is very effective. PMID:21589885

  12. Vaginal recurrence more than 17 years after hysterectomy and adjuvant treatment for uterine carcinoma with successful salvage brachytherapy: a case report.

    PubMed

    Yechieli, Raphael; Robbins, Jared R; Schultz, Daniel; Munkarah, Adnan; Elshaikh, Mohamed A

    2011-04-18

    Although the majority of recurrences occur within the first 3 years of hysterectomy for endometrioid carcinoma, we report herein a successful salvage vaginal brachytherapy in a patient with endometrioid uterine carcinoma which recurred more than 17 years after initial treatment. A 61-year-old female was diagnosed with endometrioid adenocarcinoma of the uterus and treated with TAH-BSO, followed by adjuvant external beam radiation therapy (EBRT) to the whole pelvis. After remaining free of any recurrent or metastatic disease for more than 17 years, she was diagnosed with isolated vaginal cuff recurrence and successfully treated with a salvage high-dose-rate intracavitary vaginal brachytherapy. The patient remained disease free until her death from unrelated causes 7 years later. To the best of our knowledge, this case represents the longest time to recurrence of endometrial cancer in someone who had been treated with TAH-BSO and adjuvant pelvic EBRT. This case highlights that even with adjuvant therapy, late recurrences may occur, and successful salvage brachytherapy is very effective.

  13. Interstitial high-dose-rate brachytherapy as salvage treatment for locally recurrent prostate cancer after definitive radiation therapy: Toxicity and 5-year outcome.

    PubMed

    Jiang, Ping; van der Horst, Christof; Kimmig, Bernhard; Zinsser, Fabian; Poppe, Bjoern; Luetzen, Ulf; Juenemann, Klaus-Peter; Dunst, Juergen; Siebert, Frank-André

    We report our results with interstitial high-dose-rate brachytherapy (HDR-BT) as a salvage therapy option after external beam therapy with or without BT. Emphasis was put on toxicity and 5-year outcome. From 2003 to 2011, 29 patients with local failure after previous radiotherapy for prostate cancer were treated with salvage interstitial HDR-BT. The diagnosis of local recurrence was made on the basis of choline positron emission tomography. Salvage HDR-BT was given in three fractions with a single dose of 10 Gy per fraction and weekly. The target volume covered the peripheral zone of the prostate and the positron emission tomography-positive area. Acute and late toxicities were documented according to common terminology criteria for adverse events (CTCAE v 4.0). Twenty-two patients with minimum followup of 60 months were analyzed. The 5-year overall survival was 95.5% with a disease-specific survival of 100%. The 5-year biochemical control was 45%. Late grade 2 gastrointestinal toxicities were observed in two patients (9%). No grade 3 or higher gastrointestinal late toxicities were observed. Urinary incontinence found in 2 patients (9%) and grade 2 obstruction of urinary tract occurred in one patient (4%). Interstitial HDR-BT was feasible and effective in the treatment of locally recurrent prostate cancer after definitive radiotherapy. The long-term toxicity was low and acceptable. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Salvage microbiology: opportunities and challenges in the detection of bacterial pathogens following initiation of antimicrobial treatment

    PubMed Central

    Farrell, John J.; Hujer, Andrea M.; Sampath, Rangarajan; Bonomo, Robert A.

    2015-01-01

    Broad-range 16S ribosomal RNA gene PCR coupled with Sanger sequencing was originally employed by soil scientists and was subsequently adapted for clinical applications. PCR coupled with electrospray ionization mass spectrometry has also progressed from initial applications in the detection of organisms from environmental samples into the clinical realm and has demonstrated promise in detection of pathogens in clinical specimens obtained from patients with suspected infection but negative cultures. We review studies of multiplex PCR, 16S ribosomal RNA gene PCR and sequencing and PCR coupled with electrospray ionization mass spectrometry for detection of bacteria in specimens that were obtained from patients during or after administration of antibiotic treatment, and examine the role of each for assisting in antimicrobial treatment and stewardship efforts. Following an exploration of the available data in this field we discuss the opportunities that the preliminary investigations reveal, as well as the challenges faced with implementation of these strategies in clinical practice. PMID:25523281

  15. Epidemiological control of drug resistance and compensatory mutation under resistance testing and second-line therapy.

    PubMed

    Saddler, Clare A; Wu, Yue; Valckenborgh, Frank; Tanaka, Mark M

    2013-12-01

    The fitness cost of antibiotic resistance in the absence of treatment raises the possibility that prudent use of drugs may slow or reverse the rise of resistance. Unfortunately, compensatory mutations that lower this cost may lead to entrenched resistance. Here, we develop a mathematical model of resistance evolution and compensatory mutation to determine whether reversion to sensitivity can occur, and how disease control might be facilitated by a second-line therapy. When only a single antibiotic is available, sensitive bacteria reach fixation only under treatment rates so low that hardly any cases are treated. We model a scenario in which drug sensitivity can be accurately tested so that a second-line therapy is administered to resistant cases. Before the rise of resistance to the second drug, disease eradication is possible if resistance testing and second-line treatment are conducted at a high enough rate. However, if double drug resistance arises, the possibility of disease eradication is greatly reduced and compensated resistance prevails in most of the parameter space. The boundary separating eradication from fixation of compensated resistance is strongly influenced by the underlying basic reproductive number of the pathogen and drug efficacy in sensitive cases, but depends less on the resistance cost and compensation. When double resistance is possible, the boundary is affected by the relative strengths of resistance against the two drugs in the double-resistant-compensated strain. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Microdissection testicular sperm extraction and salvage hormonal treatment in patients with postchemotherapy azoospermia.

    PubMed

    Shiraishi, Koji; Matsuyama, Hideyasu

    2014-01-01

    To investigate the efficacy of microdissection testicular sperm extraction (micro-TESE) in patients with postchemotherapy azoospermia (PCA), we reviewed our results of micro-TESE combined with intracytoplasmic sperm injection, which are the most commonly used fertility treatments. Furthermore, we investigated the efficacy of hormonal therapy for men who failed to recover sperm after micro-TESE. Twenty-six patients with PCA with the mean age of 34.6 years (range, 23-42) were included in this study. The cancer types included testicular cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, neuroblastoma, osteosarcoma, and malignant pheochromocytoma. The mean interval from chemotherapy to micro-TESE was 14.8 years (range, 7-25), and the mean age of the female partners was 34.1 years. Sperm were retrieved in 11 (42%) of the patients. Six patients who did not obtain successful sperm retrieval underwent human chorionic gonadotropin-based hormonal therapy, and sperm were retrieved from 2 patients by a second micro-TESE. In total, 7 (27%) pregnancies and 5 (19%) live birth deliveries were achieved. Patients with PCA after testicular cancer treatment were able to achieve a high rate (75%) of sperm retrieval and that exposure to alkylating agents resulted in lower sperm retrieval rates. Micro-TESE-intracytoplasmic sperm injection is an effective fertility treatment for patients with PCA. Furthermore, patients who could not achieve successful sperm retrieval by micro-TESE might obtain improved outcomes with hormonal therapy, indicating that these treatments might provide the patients with PCA with the opportunity to retrieve sperm and father a child. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients.

    PubMed

    Silvani, Antonio; Lamperti, Elena; Gaviani, Paola; Eoli, Marica; Fiumani, Anna; Salmaggi, Andrea; Falcone, Chiara; Filippini, Graziella; Botturi, Andrea; Boiardi, Amerigo

    2008-04-01

    The purpose of this study was to evaluate safety and efficacy of Procarbazine (PCB) and fotemustine (FTM) combination in the treatment of pre-temozolomide treated, recurrent GBM patients. The primary end-point was progression free survival at 6 months (PFS-6). Secondary end-points were overall survival, response rates (CR + PR) and toxicity. About 54 patients (41 men and 13 women) aged 26-68 years (median age, 53.5 years) with recurrent GBM were treated. PCB was administered as an oral dosage of 450 mg on days 1-2 and a total dose of 300 mg on day 3. FTM was administered on day 3, 3 h after the last PCB intake at a dose of 110 mg/mq/BSA. The treatment was repeated every 5 weeks. Treatment was continued for a maximum of six cycles or until disease progression. After two cycles of chemotherapy: 6 patients (11.2%) experienced a neuroradiographic partial response (PR), 29 patients (53.7%) had stable disease (SD), and 19 patients (35.1%) had progressive disease (PD). For the whole group of patients, the median PFS was 19.3 weeks (95% CI, 14.1-24.4 weeks), and PFS-6 was 26.7% (95% CI, 10.6-42.8%). Overall MST from the beginning of PCB + FTM chemotherapy was 28.7 weeks (95% CI, 24.8-32.7 weeks). At 6 and 12 months, 64.4% (95% CI, 51.5-77.3%) and 23.6% (95% CI, 10.1-37.1%) of patients were alive. The median survival time calculated from the first diagnosis was 20.8 months (95% CI, 16.7-24.8). We concluded that the PCB + FTM combination as done in the current trial for patients with recurrent GBM after treatment with TMZ showed some benefit with regards to increased survival and that a Phase III trial is warranted.

  18. Hyperbaric oxygen therapy as salvage treatment for sudden sensorineural hearing loss: a prospective controlled study.

    PubMed

    Pezzoli, M; Magnano, M; Maffi, L; Pezzoli, L; Marcato, P; Orione, M; Cupi, D; Bongioannini, G

    2015-07-01

    The most commonly used treatment for sensorineural sudden hearing loss (SSHL) in clinical practice is the administration of steroids; however, a favorable result is not always obtained. We studied 58 patients who failed to recover after primary treatment with IV steroids, 44 of these met our inclusion criteria (mean age 50.7, 27 males, range 30-74). We treated 23 patients (mean age 47.3, 16 males, age range 22-74) with hyperbaric oxygen therapy (HBO) (2.5 ATA for 60 min for 15 treatments), while 21 (mean age 54.5, 11 males, age range 22-71) patients refused to be treated and served as a non-randomized control group. Patients treated with HBO had a mean improvement of 15.6 dB (SD ± 15.3), with 1 of them completely healed, 5 with a good recovery, 10 with a fair recovery and 7 unchanged. Patients who were not treated had a spontaneous mean improvement of 5.0 dB (SD ± 11.4) with 3 patients with a good recovery, 1 patient with a fair recovery and 17 patients unchanged. Mean improvement was significantly better in patients treated with HBO compared to controls (p = 0.0133). Patients with worst hearing had the greater degree of improvement whether or not they were treated in the first 10 days after the onset of the hearing loss or between 11 and 30 days. In conclusion, hyperbaric oxygen therapy can lead to significant improvement of pure tone hearing thresholds in patients with SSHL who failed primary corticosteroid treatment and are within 4 weeks of the onset of deafness.

  19. Successful Salvage Treatment of Resistant Acute Antibody-Mediated Kidney Transplant Rejection with Eculizumab.

    PubMed

    Khan, Saif A; Al-Riyami, Dawood; Al-Mula Abed, Yasser W; Mohammed, Saja; Al-Riyami, Marwa; Al-Lawati, Nabil M

    2016-08-01

    Antibody-mediated rejection (ABMR) jeopardises short- and long-term transplant survival and remains a challenge in the field of organ transplantation. We report the first use of the anticomplement agent eculizumab in Oman in the treatment of a 61-year-old female patient with ABMR following a living unrelated kidney transplant. The patient was admitted to the Sultan Qaboos University Hospital in Muscat, Oman, in 2013 on the eighth day post-transplantation with serum creatinine (Cr) levels of 400 µmol/L which continued to rise, necessitating haemodialysis. A biopsy indicated ABMR with acute cellular rejection. No improvement was observed following standard ABMR treatment and she continued to require dialysis. Five doses of eculizumab were administered over six weeks with a subsequent dramatic improvement in renal function. The patient became dialysis-free with serum Cr levels of 119 µmol/L within four months. This case report indicates that eculizumab is a promising agent in the treatment of ABMR.

  20. Rill erosion in burned and salvage logged western montane forests: Effects of logging equipment type, traffic level, and slash treatment

    Treesearch

    J. W. Wagenbrenner; P. R. Robichaud; R. E. Brown

    2016-01-01

    Following wildfires, forest managers often consider salvage logging burned trees to recover monetary value of timber, reduce fuel loads, or to meet other objectives. Relatively little is known about the cumulative hydrologic effects of wildfire and subsequent timber harvest using logging equipment. We used controlled rill experiments in logged and unlogged (control)...

  1. Successful salvage treatment of native valve Enterococcus faecalis infective endocarditis with telavancin: two case reports.

    PubMed

    Thompson, Mickala M; Hassoun, Ali

    2017-07-01

    Infective endocarditis (IE) one-year mortality rates approach 40%. Here, we report two native valve Enterococcus faecalis IE cases in patients successfully treated with telavancin. An 88-year-old with mitral valve endocarditis and a penicillin allergy, initially treated with intravenous vancomycin, was switched to telavancin. A 69-year-old, who previously received amoxicillin and intravenous vancomycin for presumed enterococcal bacteraemia, was diagnosed with dual valve endocarditis for which he received telavancin. Both received six weeks of telavancin. Neither had telavancin-related adverse events, evidence of infection at six months, nor required telavancin dosing adjustments. Documented use of novel treatments for serious enterococcal infections is needed.

  2. Number of infrapopliteal arteries undergoing endovascular treatment is not associated with the limb salvage rate in patients with critical limb ischemia.

    PubMed

    de Athayde Soares, Rafael; Matielo, Marcelo Fernando; Brochado Neto, Francisco Cardoso; Martins Cury, Marcus Vinícius; Marques, Régis Campos; Sacilotto, Roberto

    2016-11-01

    The objective of this study was to determine whether the number of infrapopliteal arteries undergoing endovascular treatment is associated with the limb salvage rate in patients with critical limb ischemia (CLI). This was a retrospective, consecutive cohort study of CLI patients who underwent infrapopliteal angioplasty at the Vascular and Endovascular Surgery Service of the Hospital do Servidor Público Estadual, São Paulo, between January 2009 and January 2013. The primary outcome variable was the limb salvage rate. The secondary outcome variables were patency, survival, plantar arch quality, and operative mortality rate. Overall, 109 infrapopliteal angioplasties were performed in 92 patients, and the initial technical success rate was 95.6%. Based on the analyses of the arteriography of the endovascular procedures, the patients were classified into two groups according to whether they had undergone endovascular treatment of one artery (group 1) or two arteries (group 2). The mean outpatient follow-up time was 430 ± 377.5 days. The analyses were performed at 180 and 360 days. There were 72 angioplasties (66%) in group 1 and 37 (34%) in group 2. Hypertension was more frequent in group 1 (93.1%) than in group 2 (78.4%; P = .03). Other clinical characteristics were similar in both groups. Regarding postoperative complications, the incidence of acute kidney failure was lower in group 1 (0% vs 8.1%, respectively; P = .037). The limb salvage rate at 360 days was similar in groups 1 and 2 (89.4% vs 89.3%, respectively; P = .595). The secondary patency rate at 360 days was also similar in groups 1 and 2 (59.9% vs 60.9%, respectively; P = .571). The perioperative mortality rate was lower in group 1 (4.2% vs 16.2%, respectively; P = .039), but the survival rate at 360 days was similar in both groups (82.1% vs 75.1%, respectively; P = .931). The frequencies of complete, incomplete, and absent plantar arch were similar in both groups. The estimated limb

  3. Valproic acid improves second-line regimen of small cell lung carcinoma in preclinical models

    PubMed Central

    Hubaux, Roland; Vandermeers, Fabian; Cosse, Jean-Philippe; Crisanti, Cecilia; Kapoor, Veena; Albelda, Steven M.; Mascaux, Céline; Delvenne, Philippe; Hubert, Pascale

    2015-01-01

    With 5-year survival rates below 5%, small cell lung carcinoma (SCLC) has very poor prognosis and requires improved therapies. Despite an excellent overall response to first-line therapy, relapses are frequent and further treatments are disappointing. The goal of the study was to improve second-line therapy of SCLC. The effect of chemotherapeutic agents was evaluated in cell lines (apoptosis, reactive oxygen species, and RNA and protein expression) and in mouse models (tumour development). We demonstrate here that valproic acid, a histone deacetylase inhibitor, improves the efficacy of a second-line regimen (vindesine, doxorubicin and cyclophosphamide) in SCLC cells and in mouse models. Transcriptomic profiling integrating microRNA and mRNA data identifies key signalling pathways in the response of SCLC cells to valproic acid, opening new prospects for improved therapies. PMID:27730151

  4. Second-line angiogenesis inhibition in metastatic colorectal cancer patients: Straightforward or overcrowded?

    PubMed

    Giampieri, Riccardo; Caporale, Marta; Pietrantonio, Filippo; De Braud, Filippo; Negri, Francesca V; Giuliani, Francesco; Pusceddu, Valeria; Demurtas, Laura; Restivo, Angelo; Fontanella, Caterina; Aprile, Giuseppe; Cascinu, Stefano; Scartozzi, Mario

    2016-04-01

    Although the number of therapeutic options targeting tumour angiogenesis is becoming increasingly relevant, the question of the optimal choice for second-line anti-angiogenic inhibition in combination with chemotherapy for metastatic colorectal cancer patients remains largely unanswered. In fact the lack of head to head comparison between consolidated options such as bevacizumab and new treatment alternatives such as aflibercept and ramucirumab makes the selection in the clinical practice challenging, particularly when the patient has already received an anti-angiogenic-based combination up-front. In the following pages we described the biological scenario validating second-line angiogenesis inhibition in colorectal cancer along with potential mechanism of resistance. We also critically described the available evidence recommending the use of the bevacizumab, aflibercept and ramucirumab in this setting with the final aim to guide the choice in the clinical practice.

  5. A review of second-line chemotherapy and prognostic models for disseminated germ cell tumors.

    PubMed

    Voss, Martin H; Feldman, Darren R; Bosl, George J; Motzer, Robert J

    2011-06-01

    Despite an excellent prognosis even for patients with disseminated disease, about 20% to 30% of men with advanced germ cell tumors are refractory to first-line chemotherapy or experience disease recurrence after an initial remission with such treatment. Many of these are cured with conventional dose cisplatin/ifosfamide-based regimen or high-dose chemotherapy with stem cell rescue. Controversy exists regarding the optimal choice between these 2 second-line approaches, and available data for each is reviewed here. Clinical factors can help prognosticate patients, and recently an international effort developed a prognostic model for the second-line setting that can be universally applied in future studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. [Endoscopic salvage treatment for optic neuropathy caused by sinonasal fibro-osseous lesions].

    PubMed

    Deng, J; Chen, F H; Lai, Y Y; Shi, J B

    2017-09-07

    Objective: To summarize the surgical techniques, benefits and limitations of transnasal endoscopic resection and optic nerve decompression for patients with optic neuropathy caused by fibro-osseous lesions. Methods: Eight patients with optic neuropathy caused by fibro-osseous lesions who accepted endoscopic surgery of either resection of the lesion or decompression of optic nerve in Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University from 2007 to 2016 were retrospectively reviewed and followed until April, 2017. Analyses were performed on the pathology type, disease extent and disease duration, especially on the visual acuity and visual field changes before and after surgery. Results: Eight patients (5 male and 3 female) were included in this study, with a median age of 12 years old (8-19 years old). The median disease duration was 12 months (1-72 months). The visual acuity (VA) of five patients (40 cm/FC, 0.2, 0.1, 0.2, 10 cm/FC, respectively) improved after surgery (0.1, 0.3, 1.2, 0.1, 0.6, respectively), and one patient had no change of VA after the surgery. Two patients (0.02, hand movement, before surgery) became deprived of light perception (VA=0) immediately after surgery. One patient complicated with intra orbital hemorrhage because of anterior artery injury. No complications of cerebral spinal fluid leak, intra-ocular muscle injury, intra-cranial hemorrhage or brain tissue injury occurred. Conclusion: For the treatment of optic neuropathy caused by fibro-osseous lesions, transnasal endoscopic surgery might have a good outcome.

  7. Impella 5.0 as a Second-Line Mechanical Circulatory Support Strategy After Extracorporeal Life Support.

    PubMed

    Schibilsky, David; Kruger, Tobias; Lausberg, Henning F; Eisenlohr, Christoph; Haller, Christoph; Nemeth, Attila; Schibilsky, Barbara; Haeberle, Helene; Rosenberger, Peter; Walker, Tobias; Schlensak, Christian

    2016-09-01

    The catheter-based Impella 5.0 left ventricular assist device is a powerful and less invasive alternative for patients in cardiogenic shock. The use as second-line therapy in patients with precedent extracorporeal life support (ECLS) has not been described before now. We analyzed our experience of consecutive patients treated with this alternative strategy. From April 2014 to December 2014, eight patients had been implanted as a second-line option after ECLS support. The reason for the change from ECLS to Impella 5.0 was absence of cardiac recovery for primary weaning and complications of ECLS therapy. The mean time of ECLS support prior to Impella implantation was 12 ± 7 days. The implantation of the Impella 5.0/CP was technically successful in all patients, and the ECLS could be explanted in all eight patients who received Impella implantation as a second-line treatment. The second-line Impella 5.0 therapy resulted in two patients who turned into left ventricular assist device (LVAD) candidates, two primary weaning candidates, and four patients who died in the setting of sepsis or absent cardiac recovery and contraindications for durable LVAD therapy. Thereby, the overall hospital discharge survival as well as the 180-day survival was 50% for Impella 5.0 implantations as second-line procedure after ECLS. The latest follow-up survival of this second-line strategy after ECLS was three out of eight, as one patient died after 299 days of LVAD support due to sepsis. The use of Impella 5.0 constitutes a possible second-line therapeutic option for those patients who do not show cardiac recovery during prolonged ECLS support or suffer from complications of ECLS therapy. This treatment allows additional time for decisions regarding cardiac recovery or indication for durable LVAD therapy.

  8. Viral suppression rates in salvage treatment with raltegravir improved with the administration of genotypic partially active or inactive nucleoside/tide reverse transcriptase inhibitors.

    PubMed

    Scherrer, Alexandra U; von Wyl, Viktor; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Bürgisser, Philippe; Garzoni, Christian; Hirschel, Bernard; Cavassini, Matthias; Battegay, Manuel; Vernazza, Pietro L; Bernasconi, Enos; Ledergerber, Bruno; Günthard, Huldrych F

    2011-05-01

    Nucleoside reverse transcriptase inhibitors (NRTIs) are often administered in salvage therapy even if genotypic resistance tests (GRTs) indicate high-level resistance, but little is known about the benefit of these additional NRTIs. The effect of <2 compared with 2 NRTIs on viral suppression (HIV-1 RNA < 50 copies/mL) at week 24 was studied in salvage patients receiving raltegravir. Intent-to-treat and per-protocol analyses were performed; last observation carried forward imputation was used to deal with missing information. Logistic regressions were weighted to create a pseudopopulation in which the probability of receiving <2 and 2 NRTIs was unrelated to baseline factors predicting treatment response. One-hundred thirty patients were included, of whom 58.5% (n = 76) received <2 NRTIs. NRTIs were often replaced by other drug classes. Patients with 2 NRTIs received less additional drug classes compared with patients with <2 NRTIs [median (IQR): 1 (1-2) compared with 2 (1-2), P Wilcoxon < 0.001]. The activity of non-NRTI treatment components was lower in the 2 NRTIs group compared with the <2 NRTIs group [median (IQR) genotypic sensitivity score: 2 (1.5-2.5) compared with 2.5 (2-3), P Wilcoxon < 0.001]. The administration of <2 NRTIs was associated with a worse viral suppression rate at week 24. The odds ratios were 0.34 (95% confidence interval: 0.13 to 0.89, P = 0.027) and 0.19 (95% confidence interval: 0.05 to 0.79, P = 0.023) when performing the last observation carried forward and the per-protocol approach, respectively. Our findings showed that partially active or inactive NRTIs contribute to treatment response, and thus the use of 2 NRTIs in salvage regimens that include raltegravir seems warranted.

  9. Salvage Therapy of Refractory Hemophagocytic Lymphohistiocytosis with Alemtuzumab

    PubMed Central

    Marsh, Rebecca A.; Allen, Carl E.; McClain, Kenneth L.; Weinstein, Joanna L.; Washko, Julie Kanter; Skiles, Jodi; Lee, Nadine D.; Khan, Shakila P.; Lawrence, Julia; Mo, Jun Q.; Bleesing, Jack J.; Filipovich, Alexandra H.; Jordan, Michael B.

    2012-01-01

    Background Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that remains difficult to treat. Even with current standard HLH therapy, only approximately half of patients will experience complete resolution of disease, and early mortality remains a significant problem. Salvage therapies have been described only in limited case reports, and there are no large studies of second-line therapies. Procedure We reviewed the charts of 22 pediatric and adult patients who received alemtuzumab for the treatment of refractory HLH at our center or in consultation with our group. Results Patients had received conventional therapies for a median of 8 weeks (range 2–70) prior to alemtuzumab, and treatment immediately prior to alemtuzumab included dexamethasone (100%), etoposide (77%), cyclosporine (36%), intrathecal hydrocortisone +/− methotrexate (23%), methylprednisolone (9%), and rituximab (14%). Patients received a median dose of 1mg/kg alemtuzumab (range 0.1–8.9mg/kg) divided over a median of 4 days (range 2–10). Fourteen patients experienced an overall partial response, defined as at least a 25% improvement in 2 or more quantifiable symptoms or laboratory markers of HLH 2 weeks following alemtuzumab (64%). Five additional patients had a 25% or greater improvement in a single quantifiable symptom or laboratory marker of HLH (23%). Seventy-seven percent of patients survived to undergo allogeneic hematopoietic cell transplantation. Patients experienced an acceptable spectrum of complications, including CMV and adenovirus viremia. Conclusion Alemtuzumab appears to be an effective salvage agent for refractory HLH, leading to improvement and survival to HCT in many patients. Prospective trials to define optimal dosing levels, schedules, and responses are needed. PMID:22522603

  10. (68) Ga-PSMA-PET for radiation treatment planning in prostate cancer recurrences after surgery: Individualized medicine or new standard in salvage treatment.

    PubMed

    Habl, Gregor; Sauter, Katharina; Schiller, Kilian; Dewes, Sabrina; Maurer, Tobias; Eiber, Matthias; Combs, Stephanie E

    2017-06-01

    (68) Ga-PSMA-PET imaging is a novel promising diagnostic tool to locate early biochemical failure after radical prostatectomy (RP) in prostate cancer (PC) patients. Exact knowledge of the relapse location may result in changes of the therapy concept aside from changes to the TNM stage. To gain data for this approach, we evaluated PC patients receiving (68) Ga-PSMA-PET imaging before salvage radiotherapy (RT). In this study, 100 patients with biochemical failure after RP± prior RT who underwent (68) Ga-PSMA PET/CT or PET/MRI were evaluated undergoing salvage RT in our department. We analyzed TNM staging changes due to (68) Ga-PSMA-PET imaging and its influence on RT planning and treatment. Uptake indicative for tumor recurrence in (68) Ga-PSMA-PET was found in 76% of the patients with biochemical recurrent PC. Median PSA level was 1.0 ng/mL (range 0.12-14.7 ng/mL). Of these, 80% showed no morphological correlate in the corresponding CT or MRI. A 43% of all patients experienced a change in TNM stage due to (68) Ga-PSMA-PET imaging. Patients had changes from Tx to rcT+ (28%), 12% from pN0 to rcN1, 1% from pN0/cM0 to rcM1a, and 8% from cM0 to rcM1b. Due to the additional knowledge of (68) Ga-PSMA-PET imaging, initial planned RT planning was adapted in 59% of all cases. An additional simultaneous integrated boost (SIB) to the prostate bed or lymph nodes was given to 32% and 63%, respectively. Ten patients received stereotactic body RT (SBRT) to single bone metastases. (68) Ga-PSMA-PET imaging showed a high clinical impact on staging and RT management in patients with biochemically recurrent PC, even at low serum PSA levels. With 43% changes in staging and 59% in radiotherapy planning (68) Ga-PSMA-PET could lead to an indispensable tool in guiding radiation treatment in recurrent PC. © 2017 Wiley Periodicals, Inc.

  11. Salvage in the Classroom

    ERIC Educational Resources Information Center

    McCollum, Dannel

    1977-01-01

    Describes the development of a program to establish in-school salvage systems for school-generated and nonschool-generated waste materials. Students from conservation classes became involved in collecting waste from "recycle" boxes in every classroom, in field trips, newspaper drives, and salvage of aluminum cans. (CS)

  12. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: results from the TREAT Asia HIV observational database.

    PubMed

    Boettiger, David C; Nguyen, Van K; Durier, Nicolas; Bui, Huy V; Heng Sim, Benedict L; Azwa, Iskandar; Law, Matthew; Ruxrungtham, Kiat

    2015-02-01

    Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources, it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients.

  13. Prevalence of and risk factors for resistance to second-line drugs in people with multidrug-resistant tuberculosis in eight countries: a prospective cohort study.

    PubMed

    Dalton, Tracy; Cegielski, Peter; Akksilp, Somsak; Asencios, Luis; Campos Caoili, Janice; Cho, Sang-Nae; Erokhin, Vladislav V; Ershova, Julia; Gler, Ma Tarcela; Kazennyy, Boris Y; Kim, Hee Jin; Kliiman, Kai; Kurbatova, Ekaterina; Kvasnovsky, Charlotte; Leimane, Vaira; van der Walt, Martie; Via, Laura E; Volchenkov, Grigory V; Yagui, Martin A; Kang, Hyungseok; Akksilp, Rattanawadee; Sitti, Wanlaya; Wattanaamornkiet, Wanpen; Andreevskaya, Sofia N; Chernousova, Larisa N; Demikhova, Olga V; Larionova, Elena E; Smirnova, Tatyana G; Vasilieva, Irina A; Vorobyeva, Alena V; Barry, Clifton E; Cai, Ying; Shamputa, Isdore C; Bayona, Jaime; Contreras, Carmen; Bonilla, Cesar; Jave, Oswaldo; Brand, Jeannette; Lancaster, Joey; Odendaal, Ronel; Chen, Michael P; Diem, Lois; Metchock, Beverly; Tan, Kathrine; Taylor, Allison; Wolfgang, Melanie; Cho, Eunjin; Eum, Seok Yong; Kwak, Hyun Kyung; Lee, Jiim; Lee, Jongseok; Min, Seonyeong; Degtyareva, Irina; Nemtsova, Evgenia S; Khorosheva, Tatiana; Kyryanova, Elena V; Egos, Grace; Perez, Ma Therese C; Tupasi, Thelma; Hwang, Soo Hee; Kim, Chang-ki; Kim, Su Young; Lee, Hee Jeong; Kuksa, Liga; Norvaisha, Inga; Skenders, Girts; Sture, Ingrida; Kummik, Tiina; Kuznetsova, Tatiana; Somova, Tatiana; Levina, Klavdia; Pariona, Gustavo; Yale, Gloria; Suarez, Carmen; Valencia, Eddy; Viiklepp, Piret

    2012-10-20

    The prevalence of extensively drug-resistant (XDR) tuberculosis is increasing due to the expanded use of second-line drugs in people with multidrug-resistant (MDR) disease. We prospectively assessed resistance to second-line antituberculosis drugs in eight countries. From Jan 1, 2005, to Dec 31, 2008, we enrolled consecutive adults with locally confirmed pulmonary MDR tuberculosis at the start of second-line treatment in Estonia, Latvia, Peru, Philippines, Russia, South Africa, South Korea, and Thailand. Drug-susceptibility testing for study purposes was done centrally at the Centers for Disease Control and Prevention for 11 first-line and second-line drugs. We compared the results with clinical and epidemiological data to identify risk factors for resistance to second-line drugs and XDR tuberculosis. Among 1278 patients, 43·7% showed resistance to at least one second-line drug, 20·0% to at least one second-line injectable drug, and 12·9% to at least one fluoroquinolone. 6·7% of patients had XDR tuberculosis (range across study sites 0·8-15·2%). Previous treatment with second-line drugs was consistently the strongest risk factor for resistance to these drugs, which increased the risk of XDR tuberculosis by more than four times. Fluoroquinolone resistance and XDR tuberculosis were more frequent in women than in men. Unemployment, alcohol abuse, and smoking were associated with resistance to second-line injectable drugs across countries. Other risk factors differed between drugs and countries. Previous treatment with second-line drugs is a strong, consistent risk factor for resistance to these drugs, including XDR tuberculosis. Representative drug-susceptibility results could guide in-country policies for laboratory capacity and diagnostic strategies. US Agency for International Development, Centers for Disease Control and Prevention, National Institutes of Health/National Institute of Allergy and Infectious Diseases, and Korean Ministry of Health and Welfare

  14. Efficacy of second-line antiretroviral therapy among people living with HIV/AIDS in Asia: Results from the TREAT Asia HIV Observational Database

    PubMed Central

    BOETTIGER, David C; NGUYEN, Van Kinh; DURIER, Nicolas; BUI, Huy Vu; SIM, Benedict Lim Heng; AZWA, Iskandar; LAW, Matthew; RUXRUNGTHAM, Kiat

    2014-01-01

    Background Roughly 4% of the 1.25 million patients on antiretroviral therapy (ART) in Asia are using second-line therapy. To maximize patient benefit and regional resources it is important to optimize the timing of second-line ART initiation and use the most effective compounds available. Methods HIV positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated. Results There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells/mm3, and median HIV viral load was 16,224 copies/mL. Patients started second-line ART before 2007 (n=105), 2007-2010 (n=147) and after 2010 (n=50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95%CI 7.1 to 10.9) and 1.1 (95%CI 0.6 to 1.9), respectively. Older age, high baseline viral load and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure. Conclusions Increased access to viral load monitoring to facilitate early detection of first-line ART failure and subsequent treatment switch is important for maximizing the durability of second-line therapy in Asia. Although second-line ART is highly effective in the region, the reported rate of failure emphasizes the need for third-line ART in a small portion of patients. PMID:25590271

  15. Effect of meropenem with or without immunoglobulin as second-line therapy for pediatric febrile neutropenia.

    PubMed

    Kobayashi, Ryoji; Suzuki, Daisuke; Sano, Hirozumi; Kishimoto, Kenji; Yasuda, Kazue; Kobayashi, Kunihiko

    2014-08-01

    Meropenem (MEPM) is widely used for treatment of febrile neutropenia. There have been many reports on MEPM for pediatric febrile neutropenia showing success rates of approximately 50-75%. Although i.v. immunoglobulin (IVIG) is widely used for treatment of infection with antibiotics, there has been no report on the efficacy of IVIG for pediatric febrile neutropenia. This prospective randomized study was therefore carried out to clarify the usefulness of MEPM with or without IVIG as second line-therapy for pediatric febrile neutropenia. A total of 61 pediatric patients with 146 episodes were judged to have failure of first-line therapy (August 2008-April 2010: cefozopran vs cefepime; April 2010-April 2012: cefepime vs piperacillin/tazobactam) for febrile neutropenia, and were randomized to MEPM and MEPM + IVIG groups. MEPM with or without IVIG as second-line therapy was effective in 68.1% of a total of 144 episodes. Success rates in the MEPM and MEPM + IVIG groups were 66.3% and 70.5%, respectively. Furthermore, success rates for patients with IgG <500 mg/dL were 62.5% in the MEPM group and 81.3% in the MEPM + IVIG group. This result, however, was not statistically significant, possibly because of the small sample size. MEPM is effective and safe for second-line treatment of febrile episodes in neutropenic pediatric patients. Moreover, IVIG is effective for patients with low serum IgG. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  16. Free Flap Salvage after Recurrent Venous Thrombosis by Means of Large-Scale Treatment with Medical Leeches

    PubMed Central

    Fujiki, Masahide; Arikawa, Masaki; Kagaya, Yu; Miyamoto, Shimpei

    2016-01-01

    Summary: An anterolateral thigh flap was salvaged using 110 medical leeches in the absence of an available vein for reanastomosis. After surgical construction of the flap for full-thickness thoracic wall reconstruction, the patient developed complete venous occlusion. Specifically, the anastomotic vein developed complete occlusion, and the internal jugular vein had a thrombus. In addition, because the lung was posterior to the flap, the angiogenic area of the flap was very small. When the medical leeches were first applied, the flap showed prominent venous congestion. However, the congestion began to resolve by day 6 of leech use, leading to complete survival of the flap. PMID:28293509

  17. Second-Line HIV Therapy Outcomes and Determinants of Mortality at the Largest HIV Referral Center in Southern Vietnam.

    PubMed

    Thao, Vu Phuong; Quang, Vo Minh; Wolbers, Marcel; Anh, Nguyen Duc; Shikuma, Cecilia; Farrar, Jeremy; Dunstan, Sarah; Chau, Nguyen Van Vinh; Day, Jeremy; Thwaites, Guy; Le, Thuy

    2015-10-01

    The growing numbers of HIV-infected patients requiring second-line antiretroviral therapy (ART) in Vietnam make essential the evaluation of treatment efficacy to guide treatment strategies.We evaluated all patients aged ≥15 years who initiated second-line ART after documented failure of first-line therapy at the Hospital for Tropical Diseases in Ho Chi Minh City. The primary outcome was time from second-line ART initiation to death, or to a new or reoccurrence of a WHO-defined immunological or clinical failure event, whichever occurred first. Risks of treatment failure and death were evaluated using Cox proportional hazards modeling.Data from 326 of 373 patients initiating second-line ART between November 2006 and August 2011 were included in this analysis. The median age was 32 years (IQR: 28-36). Eighty one percent were men. The median CD4 count was 44 cells/μL (IQR: 16-84). During a median follow-up of 29 months (IQR: 15-44), 60 (18.4%) patients experienced treatment failure, including 12 immunological failures, 4 WHO stage IV AIDS events, and 44 deaths (13.5%). Sixty percent of deaths occurred during the first 6-12 months. The Kaplan-Meier estimates of treatment failure after 1, 2, 3, and 4 years were 13.1% (95% CI: 9.2-16.8), 18.6% (95% CI: 14.0-23.1), 20.4% (95% CI: 15.4-25.1), and 22.8% (95% CI: 17.2-28.1), respectively. Older age, history of injection drug use, lower CD4 count, medication adherence <95%, and previous protease inhibitor use independently predicted treatment failure.While treatment efficacy was similar to that reported from other resource-limited settings, mortality was higher. Early deaths may be averted by prioritizing second-line therapy for those with lower CD4 counts and by improving treatment adherence support.

  18. Antihyperglycemic Medications: A Claims-Based Estimate of First-Line Therapy Use Before Initialization of Second-Line Medications.

    PubMed

    Tseng, Yi-Ju; Steinberg, Gregory; Fox, Kathe P; Armstrong, Joanne; Mandl, Kenneth D

    2017-09-13

    The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes. However, nonadherence to antihyperglycemic medication is common, and a clinician could confuse nonadherence with pharmacologic failure, potentially leading to premature prescribing of second-line therapies. We measured metformin use before second-line therapy initialization. This retrospective cross-sectional study used unidentifiable member claims data from individuals covered from 2010 to 2015 by Aetna, a U.S. health benefits company. Beneficiaries with two physician claims or one hospitalization with a type 2 diabetes diagnosis were included. Recommended use of metformin was measured by the proportion of days covered over 60 days. Through sensitivity analysis, we varied estimates of the percentage of beneficiaries who used low-cost generic prescription medication programs. A total of 52,544 individuals with type 2 diabetes were eligible. Of 22,956 patients given second-line treatment, only 1,875 (8.2%) had evidence of recommended use of metformin in the prior 60 days, and 6,441 (28.0%) had no prior claims evidence of having taken metformin. At the top range of sensitivity, only 49.5% patients could have had recommended use. Patients were more likely to be given an additional second-line antihyperglycemic medication or insulin if they were given their initial second-line medication without evidence of recommended use of metformin (P < 0.001). Despite published guidelines, second-line therapy often is initiated without evidence of recommended use of first-line therapy. Apparent treatment failures, which may in fact be attributable to nonadherence to guidelines, are common. Point-of-care and population-level processes are needed to monitor and improve guideline adherence. © 2017 by the American Diabetes Association.

  19. Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

    PubMed

    Lam, Simon W; Wai, Maya; Lau, Jessica E; McNamara, Michael; Earl, Marc; Udeh, Belinda

    2017-01-01

    Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified

  20. Levofloxacin/amoxicillin-based schemes vs quadruple therapy for Helicobacter pylori eradication in second-line

    PubMed Central

    Di Caro, Simona; Fini, Lucia; Daoud, Yayha; Grizzi, Fabio; Gasbarrini, Antonio; De Lorenzo, Antonino; Di Renzo, Laura; McCartney, Sara; Bloom, Stuart

    2012-01-01

    Worldwide prevalence of Helicobacter pylori (H. pylori) infection is approximately 50%, with the highest being in developing countries. We compared cure rates and tolerability (SE) of second-line anti-H. pylori levofloxacin/amoxicillin (LA)-based triple regimens vs standard quadruple therapy (QT). An English language literature search was performed up to October 2010. A meta-analysis was performed including randomized clinical trials comparing 7- or 10-d LA with 7-d QT. In total, 10 articles and four abstracts were identified. Overall eradication rate in LA was 76.5% (95% CI: 64.4%-97.6%). When only 7-d regimens were included, cure rate was 70.6% (95% CI: 40.2%-99.1%), whereas for 10-d combinations, cure rate was significantly higher (88.7%; 95% CI: 56.1%-109.9%; P < 0.05). Main eradication rate for QT was 67.4% (95% CI: 49.7%-67.9%). The 7-d LA and QT showed comparable efficacy [odds ratio (OR): 1.09; 95% CI: 0.63-1.87], whereas the 10-d LA regimen was significantly more effective than QT (OR: 5.05; 95% CI: 2.74-9.31; P < 0.001; I2 = 75%). No differences were reported in QT eradication rates among Asian and European studies, whereas LA regimens were more effective in European populations (78.3% vs 67.7%; P = 0.05). Incidence of SE was lower in LA therapy than QT (OR: 0.39; 95% CI: 0.18-0.85; P = 0.02). A higher rate of side effects was reported in Asian patients who received QT. Our findings support the use of 10-d LA as a simple second-line treatment for H. pylori eradication with an excellent eradication rate and tolerability. The optimal second-line alternative scheme might differ among countries depending on quinolone resistance. PMID:23155306

  1. Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer

    PubMed Central

    Fornaro, L; Cereda, S; Aprile, G; Di Girolamo, S; Santini, D; Silvestris, N; Lonardi, S; Leone, F; Milella, M; Vivaldi, C; Belli, C; Bergamo, F; Lutrino, S E; Filippi, R; Russano, M; Vaccaro, V; Brunetti, A E; Rotella, V; Falcone, A; Barbera, M A; Corbelli, J; Fasola, G; Aglietta, M; Zagonel, V; Reni, M; Vasile, E; Brandi, G

    2014-01-01

    Background: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. Methods: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. Results: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215–0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370–0.891), progression-free survival after first-line CT ⩾6 months (P=0.027; HR, 0.633; 95% CI 0.422–0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392–0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001). Conclusions: Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design. PMID:24714745

  2. Local recurrence risk after previous salvage mastectomy.

    PubMed

    Tanabe, M; Iwase, T; Okumura, Y; Yoshida, A; Masuda, N; Nakatsukasa, K; Shien, T; Tanaka, S; Komoike, Y; Taguchi, T; Arima, N; Nishimura, R; Inaji, H; Ishitobi, M

    2016-07-01

    Breast-conserving surgery is a standard treatment for early breast cancer. For ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery, salvage mastectomy is the current standard surgical procedure. However, it is not rare for patients with IBTR who have received salvage mastectomy to develop local recurrence. In this study, we examined the risk factors of local recurrence after salvage mastectomy for IBTR. A total of 118 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent salvage mastectomy without irradiation for IBTR between 1989 and 2008 were included from eight institutions in Japan. The risk factors of local recurrence were assessed. The median follow-up period from salvage mastectomy for IBTR was 4.6 years. Patients with pN2 or higher on diagnosis of the primary tumor showed significantly poorer local recurrence-free survival than those with pN0 or pN1 at primary tumor (p < 0.001). Multivariate analysis showed that the lymph node status of the primary tumor was a significantly independent predictive factor of local recurrence-free survival (p = 0.02). The lymph node status of the primary tumor might be a predictive factor of local recurrence-free survival after salvage mastectomy for IBTR. Further research and validation studies are needed. (UMIN-CTR number UMIN000008136). Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

    PubMed

    Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Giulio Favalli, Ennio; Becciolini, Andrea; Benucci, Maurizio; Gobbi, Francesca Li; Guiducci, Serena; Foti, Rosario; Mosca, Marta; Goletti, Delia

    2017-03-22

    The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies. Some previously stated variables, including the patients׳ preference, the indication for anti-tumor necrosis factor (TNF) monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. In RA, golimumab as second-line biologic has the highest level of evidence in anti-TNF failure. The switching strategy is preferable for responder patients who experience an adverse event, whereas serious or class-specific side effects should be managed by the choice of a differently targeted drug. Secondary inadequate response to etanercept (ETN) should be treated with a biologic agent other than anti-TNF. After two or more anti-TNF failures, the swapping to a different mode of action is recommended. Among non-anti-TNF targeted biologics, to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing the first anti-TNF, the switch strategy to a second is advisable, taking in account the evidence of adalimumab efficacy in patients with uveitis. The severity of psoriasis, of articular involvement, and the predominance of enthesitis and/or dactylitis may drive the choice toward ustekinumab or secukinumab in PsA, and the latter in AS. Taking in account the paucity of controlled trials

  4. Management of neuroblastoma: a study of first- and second-line chemotherapy responses, a single institution experience

    PubMed Central

    Habib, Emmad E.; El-Kashef, Amr T.; Fahmy, Ezzat S.

    2012-01-01

    Neuroblastoma is a high-grade malignancy of childhood. It is chemo- and radio-sensitive but prone to relapse after initial remission. The aim of the current study was to study the results of the first- and second-line chemotherapy on the short-term response and long-term survival of children, and to further describe the side effects of treatment. Ninety-five children with advanced neuroblastoma were included in the study, divided into two groups according to the treatment strategy: 65 were treated by first-line chemotherapy alone, and 30 children who were not responding or relapsed after first-line chemotherapy were treated by second-line chemotherapy. External beam radiotherapy was given to bone and brain secondary cancers when detected. Staging workup was performed before, during and after management. Response was documented after surgery for the primary tumor. Median follow up was 32 months (range 24–60 months). Chemothe rapy was continued until toxicity or disease progression occurred, indicating interruption of chemotherapy. Patients received a maximum of 8 cycles. Toxicity was mainly myelo-suppression, with grade II-III severity in 60% of the firstline and 70% of the second-line chemotherapy patients. Median total actuarial survival was nearly 51 months for the first-line chemotherapy group and 30 months for the second-line line group, with a statistically significant difference between the two groups (P<0.01). PMID:25992205

  5. Comparison of salvage chemoradiation versus salvage surgery for recurrent esophageal squamous cell carcinoma after definitive radiochemotherapy or radiotherapy alone.

    PubMed

    Chen, Y; Lu, Y; Wang, Y; Yang, H; Xia, Y; Chen, M; Song, H; Li, T; Li, D; Wang, J; Li, S; Wang, J

    2014-01-01

    A consensus treatment strategy for esophageal squamous cell carcinoma (ESCC) patients who recur after definitive radiochemotherapy/radiotherapy has not been established. This study compared the outcomes in ESCC patients who underwent salvage surgery, salvage chemoradiation (CRT) or best supportive care (BSC) for local recurrence. Ninety-five patients with clinical stage I to III ESCC who had completely responded to the initial definitive radiochemotherapy or radiotherapy alone and developed local recurrence were enrolled in this study. Fifty-one of them received salvage esophagectomy, and R0 resection was performed in 41 patients, 36 underwent salvage CRT, and the remaining eight patients received BSC only. The 5-year overall survival was 4.6% for the 87 patients receiving salvage surgery or CRT, while all patients in the BSC group died within 12.0 months, the difference was statistically significant (P = 0.018). The 1-, 3-, 5-year survival rates in the salvage surgery and salvage CRT groups were 45.1%, 20.0%, 6.9% and 51.7%, 12.2%, 3.1%, respectively, there was no difference of overall survival between the two groups (P = 0.697). Patients also presented with lymph node relapse had inferior survival compared to those with isolated local tumor recurrence after salvage therapy. In the salvage surgery group, infections occurred in eight patients, and three developed anastomotic leakage. In the salvage CRT group, grade 2-4 esophagitis and radiation pneumonitis was observed in 19 and 3 patients, respectively. Seven patients (19.4%) developed esophagotracheal fistula or esophageal perforation. This study of salvage CRT versus salvage surgery for recurrent ESCC after definitive radiochemotherapy or radiotherapy alone did not demonstrate a statistically significant survival difference, but the frequency of complications including esophagotracheal fistula and esophageal perforation following salvage CRT was high. © 2012 Copyright the Authors. Journal compilation © 2012

  6. Lung-cancer related chest events detected by periodical follow-up CT after stereotactic body radiotherapy for stage I primary lung cancer: retrospective analysis of incidence of lung-cancer related chest events and outcomes of salvage treatment.

    PubMed

    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro; Nogami, Naoyuki; Sugawara, Yoshifumi; Kozuki, Toshiyuki; Sawada, Shigeki; Suehisa, Hiroshi; Shinohara, Syuichi; Nakajima, Naomi; Shinkai, Tetsu

    2012-10-01

    Follow-up by chest CT is often performed routinely after stereotactic body radiotherapy (SBRT) for primary lung cancer. We investigated how often periodical chest CT detected lung-cancer related chest events (failure in the chest, new primary lung cancer), and how often chest CT follow-ups led to curative intent salvage treatment. Between 2006 and 2009, 90 stage I primary lung cancers in 86 patients received SBRT. In principle, chest CT was scheduled every 2-3 months in the first two years, and every 3-4 months thereafter. Median time to follow-up by chest CT was 26 months (1-61 months). Twenty-seven lung-cancer related chest events were detected by periodical chest CT after SBRT. The three-year lung-cancer related chest event free rate was 62 %. It was possible to apply curative-intent salvage treatment to 56 % of the lung-cancer related chest events. The two-year overall survival rate was 66 % among the 13 patients who received curative-intent salvage treatment (radiotherapy, 11; surgery, 2). Post-SBRT lung-cancer related chest events (as detected by periodical chest CT) were not uncommon (approximately 40 % at 3 years from SBRT), and it was possible to treat more than half of these lesions with curative-intent salvage treatment.

  7. Prognostic and Predictive Factors in Patients with Advanced Penile Cancer Receiving Salvage (2nd or Later Line) Systemic Treatment: A Retrospective, Multi-Center Study

    PubMed Central

    Buonerba, Carlo; Di Lorenzo, Giuseppe; Pond, Gregory; Cartenì, Giacomo; Scagliarini, Sarah; Rozzi, Antonio; Quevedo, Fernando J.; Dorff, Tanya; Nappi, Lucia; Lanzetta, Gaetano; Pagliaro, Lance; Eigl, Bernhard J.; Naik, Gurudatta; Ferro, Matteo; Galdiero, Mariano; De Placido, Sabino; Sonpavde, Guru

    2016-01-01

    Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6–12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data vs. predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment. Materials and methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS) and response rate (RR). OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models. Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI] = 16.6–39.7%) and median OS and PFS were 20 (95% CI = 20–21) and 12 (95% CI = 12, 16) weeks, respectively. Visceral metastasis (VM) and hemoglobin (Hb) ≤ 10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI) of 24 (20–40) weeks and 1-year (95% CI) OS of 13.7% (4.4–42.7%), while the 37 patients with 1 or 2 risk factors had median OS (95% CI) of 20 (16–20) weeks and 1-year (95% CI) OS of 6.7% (1.8–24

  8. Prognostic and Predictive Factors in Patients with Advanced Penile Cancer Receiving Salvage (2nd or Later Line) Systemic Treatment: A Retrospective, Multi-Center Study.

    PubMed

    Buonerba, Carlo; Di Lorenzo, Giuseppe; Pond, Gregory; Cartenì, Giacomo; Scagliarini, Sarah; Rozzi, Antonio; Quevedo, Fernando J; Dorff, Tanya; Nappi, Lucia; Lanzetta, Gaetano; Pagliaro, Lance; Eigl, Bernhard J; Naik, Gurudatta; Ferro, Matteo; Galdiero, Mariano; De Placido, Sabino; Sonpavde, Guru

    2016-01-01

    Introduction and objectives: Metastatic penile squamous cell carcinoma (PSCC) is associated with dismal outcomes with median overall survival (OS) of 6-12 months in the first-line and <6 months in the salvage setting. Given the rarity of this disease, randomized trials are difficult. Prognostic risk models may assist in rational drug development by comparing observed outcomes in nonrandomized phase II studies and retrospective data vs. predicted outcomes based on baseline prognostic factors in the context of historically used agents. In this retrospective study, we constructed a prognostic model in the salvage setting of PSCC patients receiving second or later line systemic treatment, and also explored differences in outcomes based on type of treatment. Materials and methods: We performed a chart review to identify patients with locally advanced unresectable or metastatic PSCC who received second or later line systemic treatment in centers from North America and Europe. The primary outcome was OS from initiation of treatment, with secondary outcomes being progression-free survival (PFS) and response rate (RR). OS was estimated using the Kaplan-Meier method. Cox proportional hazards regression was used to identify prognostic factors for outcomes using univariable and multivariable models. Results: Sixty-five patients were eligible. Seventeen of 63 evaluable patients had a response (27.0%, 95% confidence interval [CI] = 16.6-39.7%) and median OS and PFS were 20 (95% CI = 20-21) and 12 (95% CI = 12, 16) weeks, respectively. Visceral metastasis (VM) and hemoglobin (Hb) ≤ 10 gm/dl were consistently significant poor prognostic factors for both OS and PFS, and Hb was also prognostic for response. The 28 patients with neither risk factor had a median OS (95% CI) of 24 (20-40) weeks and 1-year (95% CI) OS of 13.7% (4.4-42.7%), while the 37 patients with 1 or 2 risk factors had median OS (95% CI) of 20 (16-20) weeks and 1-year (95% CI) OS of 6.7% (1.8-24.9%). Cetuximab

  9. Conservative treatment of a recto-urethral fistula due to salvage HIFU for local recurrence of prostate cancer, 5 years after radical prostatectomy and external beam radiotherapy.

    PubMed

    Topazio, Luca; Perugia, Claudio; Finazzi-Agro, Enrico

    2012-11-09

    Recto-urethral fistula is one of the most serious complications caused by high-intensity-focused ultrasound used as salvage treatment for recurrence of prostate cancer after brachytherapy or external beam radiotherapy (EBRT). We report the case of a recto-urethral fistula in a 68-year-old patient, who previously had undergone radical prostatectomy and EBRT for prostate cancer (pT3 N0 Mx). The fistula was treated conservatively by an indwelling Foley catheter, without the creation of an intestinal diversion. The fistula was assessed initially by a retrograde and a CT scan of the pelvis with contrast medium and reassessed periodically by means of retrograde urethrograms. To date, 24 months after this episode, no evidence of recurrence of the fistula has been found.

  10. Emergence of HIV Drug Resistance During First- and Second-Line Antiretroviral Therapy in Resource-Limited Settings

    PubMed Central

    Hosseinipour, Mina C.; Gupta, Ravindra K; Van Zyl, Gert; Eron, Joseph J.; Nachega, Jean B.

    2013-01-01

    Introduction Antiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings. Results Resistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)–based therapy suggest that 76%–90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%–72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited. Conclusions Resistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance. PMID:23687289

  11. Intensive adherence counselling for HIV-infected individuals failing second-line antiretroviral therapy in Johannesburg, South Africa.

    PubMed

    Fox, Matthew P; Berhanu, Rebecca; Steegen, Kim; Firnhaber, Cindy; Ive, Prudence; Spencer, David; Mashamaite, Sello; Sheik, Sadiyya; Jonker, Ingrid; Howell, Pauline; Long, Lawrence; Evans, Denise

    2016-09-01

    In resource-limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation. This was a single-arm study of patients on second-line protease inhibitor (PI)-based antiretroviral therapy (ART) with a HIV-1 RNA ≥400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013. Patients underwent enhanced adherence counselling. Those with improved adherence and a repeat viral load of >1000 copies/ml underwent HIV-1 drug resistance testing. We describe results using simple proportions and 95% confidence intervals. Of the 400 patients who underwent targeted adherence counselling after an elevated viral load on second-line ART, 388 (97%) underwent repeat viral load testing. Most of these (n = 249; 64%, 95% CI 59-69) resuppressed (<400 copies/ml) on second line. By the end of follow-up (1 March 2014), among the 139 (36%, 95% CI: 31-41%), who did not initially resuppress after being targeted, 106 had a viral load >400 copies/ml, 11 switched to third line, 5 were awaiting third line, 4 had died and 13 were lost to follow-up. Among the unsuppressed, 48 successfully underwent resistance testing with some resistance detected in most (41/48). Most (64%) second-line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second-line outcomes and reducing the need for third-line ART. © 2016 John Wiley & Sons Ltd.

  12. Salvage chemotherapy for adults with relapsed or refractory lymphoma in Malawi.

    PubMed

    Kaimila, Bongani; van der Gronde, Toon; Stanley, Christopher; Kasonkanji, Edwards; Chikasema, Maria; Tewete, Blessings; Fox, Paula; Gopal, Satish

    2017-01-01

    Lymphoma is highly associated with HIV in sub-Saharan Africa (SSA), which contributes to worse outcomes relative to resource-rich settings, and frequent failure of first-line chemotherapy. However, there are no second-line treatment descriptions for adults with relapsed or refractory lymphoma (RRL) in SSA. We describe HIV+ and HIV- patients with RRL receiving salvage chemotherapy in Malawi. Patients were prospectively treated at a national teaching hospital in Lilongwe, with the modified EPIC regimen (etoposide, prednisolone, ifosfamide, cisplatin) between June 2013 and May 2016, after failing prior first-line chemotherapy. Among 21 patients (18 relapsed, 3 refractory), median age was 40 years (range 16-78), 12 (57%) were male. Thirteen patients (62%) were HIV+, of whom 12 (92%) were on antiretroviral therapy (ART) at initiation of salvage chemotherapy, with median CD4 cell count 139 cells/μL (range 12-529) and 11 (85%) with suppressed HIV RNA. Median number of EPIC cycles was 3 (range 1-6), and the commonest toxicity was grade 3/4 neutropenia in 19 patients (90%). Fifteen patients responded (3 complete, 12 partial, overall response rate 71%), but durations were brief. Median overall survival was 4.5 months [95% confidence interval (CI) 2.4-5.6]. However, three patients, all HIV+, experienced sustained remissions. Tolerability, response, and survival did not differ by HIV status. The appropriateness and cost-effectiveness of this approach in severely resource-limited environments is uncertain, and multifaceted efforts to improve first-line lymphoma treatment should be emphasized, to reduce frequency with which patients require salvage chemotherapy. NCT02835911. Registered 19 January 2016.

  13. Mitomycin C and Vinorelbine for second-line chemotherapy in NSCLC – a phase II trial

    PubMed Central

    Babiak, A; Hetzel, J; Godde, F; König, H-H; Pietsch, M; Hetzel, M

    2007-01-01

    Single-agent therapy with Docetaxel or Pemetrexed is the current therapy of choice for second-line treatment in advanced non-small-cell lung cancer (NSCLC). The role of older agents was underattended over the last years. This study presents the combination of Mitomycin C and Vinorelbine in pretreated patients. Forty-two patients (stage IIIB and IV, pretreated with platinum-based chemotherapy) received 8 mg m−2 Mitomycin C on day 1 and 25 mg m−2 Vinorelbine on days 1 and 8 of a 28-day cycle. End points were objective tumour response, survival, and toxicity. Additionally, quality of life (QoL) was assessed. Five patients (11.9 %) achieved partial responses and 13 patients (31.9%) stable disease. Progression-free survival was 16 weeks. The median overall survival was 8.5 month. Eleven patients (26.2 %) suffered from grade 3 or 4 neutropenia and four patients (9.52%) from grade 3 or 4 anaemia. Evaluation of QoL showed that some items ameliorated during therapy. The therapeutic concept including Mitomycin C and Vinorelbine offers an efficacious and well-tolerated regimen, with relatively low toxicity. Objective response and survival data correlate with other second-line studies using different medication. As costs of Mitomycin C and Vinorelbine are lower compared with current drugs of choice, this regimen is likely to be cost-saving. PMID:17353918

  14. Treatment of advanced soft-tissue sarcomas using a combined strategy of high-dose ifosfamide, high-dose doxorubicin and salvage therapies.

    PubMed

    Leyvraz, S; Herrmann, R; Guillou, L; Honegger, H P; Christinat, A; Fey, M F; Sessa, C; Wernli, M; Cerny, T; Dietrich, D; Pestalozzi, B

    2006-11-20

    Having determined in a phase I study the maximum tolerated dose of high-dose ifosfamide combined with high-dose doxorubicin, we now report the long-term results of a phase II trial in advanced soft-tissue sarcomas. Forty-six patients with locally advanced or metastatic soft-tissue sarcomas were included, with age <60 years and all except one in good performance status (0 or 1). The chemotherapy treatment consisted of ifosfamide 10 g m(-2) (continuous infusion for 5 days), doxorubicin 30 mg m(-2) day(-1) x 3 (total dose 90 mg m(-2)), mesna and granulocyte-colony stimulating factor. Cycles were repeated every 21 days. A median of 4 (1-6) cycles per patient was administered. Twenty-two patients responded to therapy, including three complete responders and 19 partial responders for an overall response rate of 48% (95% CI: 33-63%). The response rate was not different between localised and metastatic diseases or between histological types, but was higher in grade 3 tumours. Median overall survival was 19 months. Salvage therapies (surgery and/or radiotherapy) were performed in 43% of patients and found to be the most significant predictor for favourable survival (exploratory multivariate analysis). Haematological toxicity was severe, including grade > or =3 neutropenia in 59%, thrombopenia in 39% and anaemia in 27% of cycles. Three patients experienced grade 3 neurotoxicity and one patient died of septic shock. This high-dose regimen is toxic but nonetheless feasible in multicentre settings in non elderly patients with good performance status. A high response rate was obtained. Prolonged survival was mainly a function of salvage therapies.

  15. Endovascular Techniques in Limb Salvage: Stents

    PubMed Central

    El-Sayed, Hosam F.

    2013-01-01

    In patients with critical limb ischemia, the first-line approach for limb salvage has shifted over the past decade from bypass surgery to endovascular intervention. Stenting for the treatment of lower-extremity arterial occlusive disease is an important tool and continues to evolve, with new stent designs and technologies that have been developed to provide superior patency rates and limb salvage. In this article, we discuss the role of peripheral stenting in the treatment of patients with critical limb ischemia, including a review of the relevant current literature and the future directions of such interventions. PMID:23805339

  16. Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for patients with advanced germ cell tumors.

    PubMed

    Nakamura, Terukazu; Ueda, Takashi; Oishi, Masakatsu; Nakanishi, Hiroyuki; Fujihara, Atsuko; Naya, Yoshio; Hongo, Fumiya; Kamoi, Kazumi; Okihara, Koji; Miki, Tsuneharu

    2015-03-01

    To investigate the efficacy of combined regimen with paclitaxel, ifosfamide and nedaplatin as salvage chemotherapy in patients with cisplatin-refractory or multiple relapsed germ cell tumors. A total of 65 patients refractory to cisplatin-based chemotherapy or with relapse after induction or salvage chemotherapy received paclitaxel 210 mg/m(2) on day 1, ifosfamide 1.2 g/m(2) on days 2-6 and nedaplatin 100 mg/m(2) on day 2 of a 3-week cycle. The primary and secondary end-points were the response rate and overall survival, respectively. Paclitaxel, ifosfamide and nedaplatin therapy was carried out as second-line therapy in 17 patients, third-line in 31 and fourth-line or later in 17. Patients were pretreated with a median of six cycles of platinum-based chemotherapy (range 3-15 cycles). The overall response rate was 62.9%, including one patient with complete response and 38 with partial response. Serum tumor marker levels normalized in 35 (56.5%) patients. Overall survival at a median follow up of 34 months was 59.3%, and median time to progression was 12 months. Multivariate analysis showed that serum tumor marker normalization was the only independent predictor of better progression-free survival and overall survival. Grade 3/4 of neutropenia, anemia and thrombocytopenia was observed in 96.9%, in 81.5%, and in 90.8% of patients, respectively. Paclitaxel, ifosfamide and nedaplatin chemotherapy appears to be effective when used as first or second salvage treatment in advanced relapsed germ cell tumors. Even after fourth-line therapy, patients with serum tumor marker normalization might have a chance for a cure. © 2014 The Japanese Urological Association.

  17. Results of a Multicenter Phase II Trial of Brentuximab Vedotin as Second-Line Therapy before Autologous Transplantation in Relapsed/Refractory Hodgkin Lymphoma.

    PubMed

    Chen, Robert; Palmer, Joycelynne M; Martin, Peter; Tsai, Nicole; Kim, Young; Chen, Bihong T; Popplewell, Leslie; Siddiqi, Tanya; Thomas, Sandra H; Mott, Michelle; Sahebi, Firoozeh; Armenian, Saro; Leonard, John; Nademanee, Auayporn; Forman, Stephen J

    2015-12-01

    This multicenter prospective phase II study examines the activity and tolerability of brentuximab vedotin as second-line therapy in patients with Hodgkin lymphoma that was relapsed or refractory after induction therapy. Brentuximab vedotin (1.8 mg/kg) was administered i.v. on day 1 of a 21-day cycle for a total of 4 cycles. Patients then proceeded to autologous hematopoietic cell transplantation (AHCT), if eligible, with or without additional salvage therapy, based on remission status after brentuximab vedotin. The primary endpoint was overall response rate (ORR). Secondary endpoints were safety, stem cell mobilization/collection, AHCT outcomes, and association of CD68(+) with outcomes. Of 37 patients, the ORR was 68% (13 complete remission, 12 partial remission). The regimen was well tolerated with few grade 3/4 adverse events, including lymphopenia (1), neutropenia (3), rash (2), and hyperuricemia (1). Thirty-two patients (86%) were able to proceed to AHCT, with 24 patients (65%) in complete remission at time of AHCT. Thirteen patients in complete remission, 4 in partial remission, and 1 with stable disease (49%) received AHCT without salvage combination chemotherapy. CD68 expression did not correlate with response to brentuximab vedotin. The median number of stem cells mobilized was 6.0 × 10(6) (range, 2.6 to 34), and median number of days to obtain minimum collection (2 × 10(6)) was 2 (range, 1 to 6). Brentuximab vedotin as second-line therapy is active, well tolerated, and allows adequate stem cell collection and engraftment. For Hodgkin lymphoma patients with relapsed/refractory disease after induction therapy, second-line brentuximab vedotin, followed by combination chemotherapy for residual disease, can effectively bridge patients to AHCT.

  18. Outcomes of second-line combination antiretroviral therapy for HIV-infected patients: a cohort study from Rio de Janeiro, Brazil.

    PubMed

    Cardoso, Sandra W; Luz, Paula M; Velasque, Luciane; Torres, Thiago S; Tavares, Isabel C; Ribeiro, Sayonara R; Moreira, Ronaldo I; Veloso, Valdilea G; Moore, Richard D; Grinsztejn, Beatriz

    2014-12-19

    World-wide, the notable expansion of HIV/AIDS treatment programs in resource-limited settings has lead to an increasing number of patients in need of second-line cART. To adequately address and prepare for this scenario, critical assessments of the outcomes of second-line cART are particularly relevant in settings where monitoring strategies may be inadequate. We evaluated virologic outcomes of second-line combination antiretroviral therapy (cART) among HIV-infected individuals from Brazil. This study was conducted at the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, at Rio de Janeiro, Brazio. For this study we included all patients who started first-line and second-line cART between 2000 and 2013. Second-line cART required a switch in the anchor drug of first-line cART. We evaluated time from second-line start to virologic failure and factors associated with increased risk of failure using multivariable Cox proportional hazards regression models. Among the 1,311 patients who started first-line cART a total of 386 patients (29.5%) initiated second-line cART, out of which 35.0% and 60.6% switched from their first-line to their second-line cART when their HIV RNA was undetectable and after documented virologic failure, respectively. At second line cART initiation, median age was 38 years [interquartile range (IQR): 31-45years]. Median CD4 count was significantly different for patients starting second-line cART undetectable [412 cells/mm3 (IQR: 240-617)] compared to those starting second-line cART after documented virologic failure [230 cells/mm3 (IQR: 118-322.5)] (p < 0.01). Median time from second-line cART initiation to failure was also significantly different for patients starting second-line cART undetectable compared to those who with documented virologic failure (log-rank test p < 0.01). Multivariable Cox models showed that younger age, lower education, and HIV RNA level were independently associated with an increased

  19. Single-institution comparative study on the outcomes of salvage cryotherapy versus salvage robotic prostatectomy for radio-resistant prostate cancer

    PubMed Central

    Vora, Anup; Agarwal, Vidhi; Singh, Prabhjot; Patel, Rupen; Rivas, Rodolfo; Nething, Josh; Muruve, Nic

    2015-01-01

    Background Although primary treatment of localized prostate cancer provides excellent oncologic control, some men who chose radiotherapy experience a recurrence of disease. There is no consensus on the most appropriate management of these patients after radiotherapy failure. In this single-institution review, we compare our oncologic outcome and toxicity between salvage prostatectomy and cryotherapy treatments. Methods From January 2004 to June 2013, a total of 23 salvage procedures were performed. Six of those patients underwent salvage prostatectomy while 17 underwent salvage cryotherapy by two high-volume fellowship-trained urologists. Patients being considered for salvage therapy had localized disease at presentation, a prostate-specific antigen (PSA) < 10 ng/mL at recurrence, life expectancy > 10 years at recurrence, and a negative metastatic workup. Patients were followed to observe cancer progression and toxicity of treatment. Results Patients who underwent salvage cryotherapy were statistically older with a higher incidence of hypertension than our salvage prostatectomy cohort. With a mean follow up of 14.1 months and 7.2 months, the incidence of disease progression was 23.5% and 16.7% after salvage cryotherapy and prostatectomy, respectively. The overall complication rate was also 23.5% versus 16.7%, with the most frequent complication after salvage cryotherapy being urethral stricture and after salvage prostatectomy being severe urinary incontinence. There were no rectal injuries with salvage prostatectomy and one rectourethral fistula in the cohort after salvage cryotherapy. Conclusion While recurrences from primary radiotherapy for prostate cancer do occur, there is no consensus on its management. In our experience, salvage procedures were generally safe and effective. Both salvage cryotherapy and salvage prostatectomy allow for adequate cancer control with minimal toxicity. PMID:27014657

  20. Systematic review of the efficacy and safety of high-intensity focussed ultrasound for the primary and salvage treatment of prostate cancer.

    PubMed

    Warmuth, Marisa; Johansson, Tim; Mad, Philipp

    2010-12-01

    High-intensity focussed ultrasound (HIFU) is an emerging minimally invasive treatment option for prostate cancer. Our aim was to assess the efficacy and safety of HIFU in both primary treatment of men with localised and locally advanced prostate cancer as well as salvage treatment of men with recurrent prostate cancer following treatment failure of radical prostatectomy or external-beam radiation therapy. We conducted a systematic literature search for studies conducted on humans and published in either English or German in several databases from 2000 to 2010. In addition, we screened several Web sites for assessments on HIFU in prostate cancer and contacted the manufacturers of the two currently available HIFU devices for supplemental information on HIFU. We included all prospective studies with >50 study participants and assessed their quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We identified 20 uncontrolled prospective case series, each of which treated between 58 and 517 patients. These studies were all conducted within the past decade. In total, 3018 patients were treated with HIFU, 93% for primary therapy and 7% for salvage HIFU. For all HIFU procedures, the biochemical disease-free survival rate at 1, 5, and 7 yr, respectively, was 78-84%, 45-84%, and 69%. The negative biopsy rate was 86% at 3 mo and 80% at 15 mo. Overall survival rates and prostate cancer-specific survival rates were 90% and 100% at 5 yr and 83% and 98% at 8 yr, respectively. Adverse events concerned the urinary tract (1-58%), potency (1-77%), the rectum (0-15%), and pain (1-6%). Quality-of-life assessment yielded controversial results. Applying the GRADE approach, the available evidence on efficacy and safety of HIFU in prostate cancer is of very low quality, mainly due to study designs that lack control groups. More research is needed to explore the use of HIFU in prostate cancer. Copyright © 2010 European Association of Urology

  1. The mangled limb: salvage versus amputation.

    PubMed

    Wolinsky, Philip R; Webb, Lawrence X; Harvey, Edward J; Tejwani, Nirmal C

    2011-01-01

    A mangled extremity is defined as a limb with injury to three of four systems in the extremity. The decision to salvage or amputate the injured limb has generated much controversy in the literature, with studies to support advantages of each approach. Various scoring systems have proved unreliable in predicting the need for amputation or salvage; however, a recurring theme in the literature is that the key to limb viability seems to be the severity of the soft-tissue injury. Factors such as associated injuries, patient age, and comorbidities (such as diabetes) also should be considered. Attempted limb salvage should be considered only if a patient is hemodynamically stable enough to tolerate the necessary surgical procedures and blood loss associated with limb salvage. For persistently hemodynamically unstable patients and those in extremis, life comes before limb. Recently, the Lower Extremity Assessment Project study attempted to answer the question of whether amputation or limb salvage achieves a better outcome. The study also evaluated other factors, including return-to-work status, impact of the level of and bilaterality of the amputation, and economic cost. There appears to be no significant difference in return to work, functional outcomes, or the cost of treatment (including the prosthesis) between the two groups. A team approach with different specialties, including orthopaedics, plastic surgery, vascular surgery and trauma general surgery, is recommended for treating patients with a mangled extremity.

  2. Cost-effectiveness of second-line antihyperglycemic therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin.

    PubMed

    Klarenbach, Scott; Cameron, Chris; Singh, Sumeet; Ur, Ehud

    2011-11-08

    Metformin is widely accepted as first-line pharmacotherapy for patients with type 2 diabetes mellitus when glycemic control cannot be achieved by lifestyle interventions alone. However, uncertainty exists regarding the optimal second-line therapy for patients whose diabetes is inadequately controlled by metformin monotherapy. Increased use of newer, more costly agents, along with the rising incidence of type 2 diabetes, carries significant budgetary implications for health care systems. We conducted this analysis to determine the relative costs, benefits and cost-effectiveness of options for second-line treatment of type 2 diabetes. We used the United Kingdom Prospective Diabetes Study Outcomes Model to forecast diabetes-related complications, quality-adjusted life-years and costs of alternative second-line therapies available in Canada for adults with type 2 diabetes inadequately controlled by metformin. We obtained clinical data from a systematic review and mixed treatment comparison meta-analysis, and we obtained information on costs and utilities from published sources. We performed extensive sensitivity analyses to test the robustness of results to variation in inputs and assumptions. Sulphonylureas, when added to metformin, were associated with the most favourable cost-effectiveness estimate, with an incremental cost of $12 757 per quality-adjusted life-year gained, relative to continued metformin monotherapy. Treatment with other agents, including thiazolidinediones and dipeptidyl peptidase-4 inhibitors, had unfavourable cost-effectiveness estimates compared with sulphonylureas. These results were robust to extensive sensitivity analyses. For most patients with type 2 diabetes that is inadequately controlled with metformin monotherapy, the addition of a sulphonylurea represents the most cost-effective second-line therapy.

  3. In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants.

    PubMed

    Soverini, Simona; De Benedittis, Caterina; Castagnetti, Fausto; Gugliotta, Gabriele; Mancini, Manuela; Bavaro, Luana; Machova Polakova, Katerina; Linhartova, Jana; Iurlo, Alessandra; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Cavo, Michele; Baccarani, Michele; Martinelli, Giovanni

    2016-08-02

    Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal

  4. Predictors of first line antiretroviral therapy failure and burden of second line antiretroviral therapy.

    PubMed

    Patrikar, Seema; Shankar, Subramanian; Kotwal, Atul; Basannar, D R; Bhatti, Vijay; Verma, Rajesh; Mukherji, Sandip

    2017-01-01

    As HIV steps into the third decade, there are more number of patients living on lifelong (antiretroviral therapy) ART and facing the threat of drug resistance with subsequent treatment failure. The aim of this study was to determine predictors of first-line ART failure with the objectives to estimate the burden of 2nd line ART. A retrospective 5-year cohort of HIV patients who were initiated on first line ART in 2008-09 was studied. Patients were followed from the time of ART initiation. Kaplan-Meier methods and Cox proportional hazards regression models were used to estimate probabilities and predictors of first line ART failure. Of the total of 195 patients initiated on first line ART, 15 patients were switched to second line ART yielding 7.69% failure rate. During the 7178 person-years of follow-up, the incidence of first line ART failure was 2.09 per 1000 person-years. The Kaplan-Meier survival analysis gave a mean survival time of 55.6 months. BMI, CD4 count at ART initiation and presence of opportunistic infections were significant predictors of first line ART failure. The burden of second line ART patients by the end of 5 years of first line ART is expected to be 151 patients. Though the first line ART failure is quite low in this study, we still need to be vigilant for lower BMI, low baseline CD4 count and occurrence of opportunistic infections to efficiently manage failures on first line ART.

  5. Image-guided high-dose-rate interstitial brachytherapy – a valuable salvage treatment approach for loco-regional recurrence of papillary thyroid cancer

    PubMed Central

    Wu, Ning; Zhao, Hongfu; Han, Dongmei; Zhao, Zhipeng; Ge, Yuxin

    2016-01-01

    Purpose To report the treatment effect of image-guided high-dose-rate (HDR) interstitial brachytherapy for refractory recurrence of papillary thyroid cancer (PTC). Case report This 66-year-old female presented with recurrence 5 years after thyroidectomy for PTC. Despite external irradiation and radioactive 131I, the lesion expanded as 3.7 × 3.0 × 2.3 cm3 and 2.0 × 1.5 × 1.5 cm3. The locoregional recurrent tumor was treated with image-guided HDR interstitial brachytherapy. The total dose of 30 Gy in 6 fractions were delivered on the whole recurrent tumor. Results Removal of the recurrent tumor was securely achieved by HDR interstitial brachytherapy guided with ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) scanning. The refractory tumor in the patients healed uneventfully after HDR interstitial brachytherapy without recurrence during the 14 months of follow-up. Conclusions The image-guided HDR interstitial brachytherapy may be a valuable salvage treatment approach for refractory recurrence of PTC. PMID:27257420

  6. Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy.

    PubMed

    Martínez, Carmen; Díaz-López, Antonio; Rodriguez-Calvillo, Mercedes; García-Sanz, Ramón; Terol, María José; Pérez-Ceballos, Elena; Jiménez, Maria J; Cantalapiedra, Alberto; Domingo-Domenech, Eva; Rodriguez, María José; Sampol, Antonia; Espeso, Manuel; López, Francisco-Javier; Briones, Javier; García, Juan F; Sureda, Anna

    2016-09-01

    The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O-ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O-ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0·001), bulky disease (P < 0·001) and B symptoms (P < 0·001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O-ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O-ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte-predominant HL. © 2016 John Wiley & Sons Ltd.

  7. Body composition and metabolic outcomes after 96 weeks of treatment with ritonavir-boosted lopinavir plus either nucleoside or nucleotide reverse transcriptase inhibitors or raltegravir in patients with HIV with virological failure of a standard first-line antiretroviral therapy regimen: a substudy of the randomised, open-label, non-inferiority SECOND-LINE study.

    PubMed

    Boyd, Mark A; Amin, Janaki; Mallon, Patrick W G; Kumarasamy, Nagalingeswaran; Lombaard, Johan; Wood, Robin; Chetchotisakd, Ploenchan; Phanuphak, Praphan; Mohapi, Lerato; Azwa, Iskandar; Belloso, Waldo H; Molina, Jean-Michel; Hoy, Jennifer; Moore, Cecilia L; Emery, Sean; Cooper, David A

    2017-01-01

    Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir. Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122. Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N

  8. Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology.

    PubMed

    Odabas, Hatice; Ulas, Arife; Aydin, Kubra; Inanc, Mevlude; Aksoy, Asude; Yazilitas, Dogan; Turkeli, Mehmet; Yuksel, Sinemis; Inal, Ali; Ekinci, Ahmet S; Sevinc, Alper; Demirci, Nebi S; Uysal, Mukremin; Alkis, Necati; Dane, Faysal; Aliustaoglu, Mehmet; Gumus, Mahmut

    2015-12-01

    Patients with advanced non-small cell lung cancer (NSCLC) generally require second-line treatment although their prognosis is poor. In this multicenter study, we aimed to detect the characteristics related to patients and disease that can predict the response to second-line treatments in advanced NSCLC. Data of 904 patients who have progressed after receiving first-line platinum-based chemotherapy in 11 centers with the diagnosis of stage IIIB and IV NSCLC and who were evaluated for second-line treatment were retrospectively analyzed. The role of different factors in determining the benefit of second-line treatment was analyzed. Median age of patients was 57 years (range 19-86). Docetaxel was the most commonly used (20.9 %, n = 189) single agent, while gemcitabine-platinum was the most commonly used (6.7 %, n = 61) combination chemotherapy regimen in second-line setting. According to survival analysis, median progression-free survival after first-line treatment (PFS2) was 3.5 months (standard error (SE) 0.2; 95 % confidence interval (CI), 3.2-3.9), median overall survival (OS) was 6.7 months (SE 0.3; 95 % CI, 6.0-7.3). In multivariate analysis, independent factors affecting PFS2 were found to be hemoglobin (Hb) level over 12 g/dl and treatment-free interval (TFI) longer than 3 months (p = 0.006 and 0.003, respectively). Similarly, in OS analysis, Hb level over 12 g/dl and time elapsed after the first-line treatment that is longer than 3 months were found to be independent prognostic factors (p = 0.0001 and 0.045, respectively). In light of these findings, determining and using the parameters for which the treatment will be beneficial prior to second-line treatment can increase success rate.

  9. Second-line afatinib administration in an elderly patient with squamous cell carcinoma

    PubMed Central

    Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul; Steinheimer, Michael; Benhassen, Naim; Sardeli, Chrysanthi; Stalikas, Nikos; Toitou, Melpomeni; Huang, Haidong

    2017-01-01

    Introduction The majority of cases of lung cancer are still diagnosed at a late stage. At this stage, palliative therapeutic options including nonspecific cytotoxic drugs, targeted therapy, or immunotherapy can be utilized. In 2016, immunotherapy was approved in Europe for squamous cell carcinoma and adenocarcinoma. Moreover, afatinib was also approved as second-line therapy for squamous cell carcinoma. Case report This article presents a case of a 76-year-old male with squamous cell carcinoma who received nab-paclitaxel as first-line therapy, and his treatment was switched to the tyrosine kinase inhibitor afatinib (40 mg) after disease progression with left lung atelectasis. After receiving afatinib for only 28 days, the atelectasis resolved. No adverse effects were observed from the afatinib therapy. Discussion In this case, afatinib 40 mg proved to be an effective alternative treatment for an elderly patient. Treatment choice should be based on the performance status of the patient, cost-effectiveness, and drug treatment guidelines. PMID:28356747

  10. Salvaging vascular access and treatment of severe limb edema: case reports on the novel use of the hemodialysis reliable outflow vascular access device.

    PubMed

    Gage, Shawn M; Ahluwalia, Hardeep S; Lawson, Jeffrey H

    2011-04-01

    We report two cases in which patients on chronic hemodialysis presented with morbid unilateral edema of the upper extremity and chest on the side of a currently functioning arteriovenous access. Both patients were known to the vascular surgery service and had previously undergone multiple attempts to create and maintain vascular access. Both severe and disabling edema and the need to maintain dialysis access were of significant concern. These patients were taken to the operating room to address both issues. Upper extremity venography with central venous runoff revealed central vein stenosis and/or occlusion resistant to angioplasty and stenting. Ultimately, these two patients received the Hemodialysis Reliable Outflow vascular access device. The experiences in this study demonstrate the novel use of a relatively new vascular access device for salvage of a malfunctioning arteriovenous fistula or graft as well as treatment of symptoms and complications resulting from long standing vascular access. Copyright © 2011 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.

  11. Sterilizing Activity of Second-Line Regimens Containing TMC207 in a Murine Model of Tuberculosis

    PubMed Central

    Lounis, Nacer; Andries, Koen; Jarlier, Vincent

    2011-01-01

    Rationale The sterilizing activity of the regimen used to treat multidrug resistant tuberculosis (MDR TB) has not been studied in a mouse model. Objective and Methods Swiss mice were intravenously inoculated with 6 log10 of Mycobacterium tuberculosis (TB) strain H37Rv, treated with second-line drug combinations with or without the diarylquinoline TMC207, and then followed without treatment for 3 more months to determine relapse rates (modified Cornell model). Measurements Bactericidal efficacy was assessed by quantitative lung colony-forming unit (CFU) counts. Sterilizing efficacy was assessed by measuring bacteriological relapse rates 3 months after the end of treatment. Main Results The relapse rate observed after 12 months treatment with the WHO recommended MDR TB regimen (amikacin, ethionamide, pyrazinamide and moxifloxacin) was equivalent to the relapse rate observed after 6 months treatment with the recommended drug susceptible TB regimen (rifampin, isoniazid and pyrazinamide). When TMC207 was added to this MDR TB regimen, the treatment duration needed to reach the same relapse rate dropped to 6 months. A similar relapse rate was also obtained with a 6-month completely oral regimen including TMC207, moxifloxacin and pyrazinamide but excluding both amikacin and ethionamide. Conclusions In this murine model the duration of the WHO MDR TB treatment could be reduced to 12 months instead of the recommended 18–24 months. The inclusion of TMC207 in the WHO MDR TB treatment regimen has the potential to further shorten the treatment duration and at the same time to simplify treatment by eliminating the need to include an injectable aminoglycoside. PMID:21408613

  12. Limb salvage surgery

    PubMed Central

    Kadam, Dinesh

    2013-01-01

    The threat of lower limb loss is seen commonly in severe crush injury, cancer ablation, diabetes, peripheral vascular disease and neuropathy. The primary goal of limb salvage is to restore and maintain stability and ambulation. Reconstructive strategies differ in each condition such as: Meticulous debridement and early coverage in trauma, replacing lost functional units in cancer ablation, improving vascularity in ischaemic leg and providing stable walking surface for trophic ulcer. The decision to salvage the critically injured limb is multifactorial and should be individualised along with laid down definitive indications. Early cover remains the standard of care, delayed wound coverage not necessarily affect the final outcome. Limb salvage is more cost-effective than amputations in a long run. Limb salvage is the choice of procedure over amputation in 95% of limb sarcoma without affecting the survival. Compound flaps with different tissue components, skeletal reconstruction; tendon transfer/reconstruction helps to restore function. Adjuvant radiation alters tissue characters and calls for modification in reconstructive plan. Neuropathic ulcers are wide and deep often complicated by osteomyelitis. Free flap reconstruction aids in faster healing and provides superior surface for offloading. Diabetic wounds are primarily due to neuropathy and leads to six-fold increase in ulcerations. Control of infections, aggressive debridement and vascular cover are the mainstay of management. Endovascular procedures are gaining importance and have reduced extent of surgery and increased amputation free survival period. Though the standard approach remains utilising best option in the reconstruction ladder, the recent trend shows running down the ladder of reconstruction with newer reliable local flaps and negative wound pressure therapy. PMID:24501463

  13. The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania

    PubMed Central

    Ramadhani, Habib O.; Bartlett, John A.; Thielman, Nathan M.; Pence, Brian W.; Kimani, Stephen M.; Maro, Venance P.; Mwako, Mtumwa S.; Masaki, Lazaro J.; Mmbando, Calvin E.; Minja, Mary G.; Lirhunde, Eileen S.; Miller, William C.

    2016-01-01

    Background. Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers’ confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods. A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI. Results. Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2–.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1–4.3). Conclusion. Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes. PMID:26949717

  14. The Effect of Switching to Second-Line Antiretroviral Therapy on the Risk of Opportunistic Infections Among Patients Infected With Human Immunodeficiency Virus in Northern Tanzania.

    PubMed

    Ramadhani, Habib O; Bartlett, John A; Thielman, Nathan M; Pence, Brian W; Kimani, Stephen M; Maro, Venance P; Mwako, Mtumwa S; Masaki, Lazaro J; Mmbando, Calvin E; Minja, Mary G; Lirhunde, Eileen S; Miller, William C

    2016-01-01

    Background.  Due to the unintended potential misclassifications of the World Health Organization (WHO) immunological failure criteria in predicting virological failure, limited availability of treatment options, poor laboratory infrastructure, and healthcare providers' confidence in making switches, physicians delay switching patients to second-line antiretroviral therapy (ART). Evaluating whether timely switching and delayed switching are associated with the risk of opportunistic infections (OI) among patients with unrecognized treatment failure is critical to improve patient outcomes. Methods.  A retrospective review of 637 adolescents and adults meeting WHO immunological failure criteria was conducted. Timely and delayed switching to second-line ART were defined when switching happened at <3 and ≥3 months, respectively, after failure diagnosis was made. Cox proportional hazard marginal structural models were used to assess the effect of switching to second-line ART on the risk of developing OI. Results.  Of 637 patients meeting WHO immunological failure criteria, 396 (62.2%) switched to second-line ART. Of those switched, 230 (58.1%) were delayed. Switching to second-line ART reduced the risk of OI (adjusted hazards ratio [AHR], 0.4; 95% CI, .2-.6). Compared with patients who received timely switch after failure diagnosis was made, those who delayed switching were more likely to develop OI (AHR, 2.2; 95% CI, 1.1-4.3). Conclusion.  Delayed switching to second-line ART after failure diagnosis may increase the risk of OI. Serial immunological assessment for switching patients to second-line ART is critical to improve their outcomes.

  15. Salvage brachytherapy and salvage surgery for recurrent oropharyngeal carcinoma following radiotherapy.

    PubMed

    Regueiro, C A; de la Torre, A; Valcárcel, F J; Magallón, R; Aragón, G

    1995-01-01

    We reviewed 21 patients who underwent salvage treatment after a biopsy of proven locally recurrent carcinoma of the oropharynx. Two of these patients underwent a second salvage treatment after failure of the first. Treatment was performed with Ir192 interstitial implant in 17 cases (13 rT1 and 4 rT2); by surgery in five cases (3 rT1, 1 rT2, 1 rTx), including two patients who had relapsed after salvage treatment with Ir192 implant; and by hyperfractionated external beam irradiation plus concomitant Tegafur chemotherapy in one case (rT3). The primary tumour was controlled in four of the 17 cases (23 per cent) treated with Ir192 implant. Of these four patients, two remained disease-free 42 and 59 months after treatment, one died of nodal metastases eight months after treatment and another of distant metastases 19 months after treatment. Four of the five cases (80 per cent) treated with surgery, including two patients who relapsed after salvage brachytherapy, remained free from local, regional and distant relapse 21, 25, 31 and 56 months after treatment.

  16. Helicobacter pylori recurrence after first- and second-line eradication therapy in Korea: the problem of recrudescence or reinfection.

    PubMed

    Kim, Seung Young; Hyun, Jong Jin; Jung, Sung Woo; Koo, Ja Seol; Yim, Hyung Joon; Lee, Sang Woo

    2014-06-01

    Recurrence of Helicobacter pylori (H. pylori) infection is the result of either recrudescence or reinfection. Annual recurrence rates per patient-year of follow-up have been reported to vary across countries. The aim of this study was to analyze recurrence rates of H. pylori after first-line and second-line eradication therapies in Korea. From 2007 to 2010, 2691 patients with H. pylori infection received first-line therapy and 573 patients who failed to respond to first-line therapy received second-line therapy. H. pylori infection and the success of eradication were assessed by endoscopic biopsy and rapid urease test or (13) C-urea breath test. All patients were advised to undergo (13) C-urea breath test or esophagogastroduodenoscopy with biopsy or rapid urease test 6 months after eradication, with annual follow-up thereafter. The eradication rate of the first-line therapy was 79.9% (1283/1605) and that of the second-line therapy was 90.4% (394/436) by per protocol analysis. Annual recurrence rates sharply declined after 2-year follow-up. Annual recurrence rates within and after 2-year follow-up were 9.3 and 2.0% after first-line therapy and those of second-line therapy were 4.5 and 2.9%, respectively. Annual recurrence rates of H. pylori showed a sharp decline after 2-year follow-up after eradication in Korean adults, which is not higher than that of Western countries. Enough time interval after treatment (i.e., 2 years) is necessary to confirm eradication, and it would not be easy to distinguish between recurrence and recrudescence before 2 years without identifying H. pylori strains. © 2014 John Wiley & Sons Ltd.

  17. Phase I/II trial evaluating concurrent carbon-ion radiotherapy plus chemotherapy for salvage treatment of locally recurrent nasopharyngeal carcinoma.

    PubMed

    Kong, Lin; Gao, Jing; Hu, Jiyi; Hu, Weixu; Guan, Xiyin; Lu, Rong; Lu, Jiade J

    2016-12-22

    After definitive chemoradiotherapy for non-metastatic nasopharyngeal carcinoma (NPC), more than 10% of patients will experience a local recurrence. Salvage treatments present significant challenges for locally recurrent NPC. Surgery, stereotactic ablative body radiotherapy, and brachytherapy have been used to treat locally recurrent NPC. However, only patients with small-volume tumors can benefit from these treatments. Re-irradiation with X-ray-based intensity-modulated radiotherapy (IMXT) has been more widely used for salvage treatment of locally recurrent NPC with a large tumor burden, but over-irradiation to the surrounding normal tissues has been shown to cause frequent and severe toxicities. Furthermore, locally recurrent NPC represents a clinical entity that is more radio-resistant than its primary counterpart. Due to the inherent physical advantages of heavy-particle therapy, precise dose delivery to the target volume(s), without exposing the surrounding organs at risk to extra doses, is highly feasible with carbon-ion radiotherapy (CIRT). In addition, CIRT is a high linear energy transfer (LET) radiation and provides an increased relative biological effectiveness compared with photon and proton radiotherapy. Our prior work showed that CIRT alone to 57.5 GyE (gray equivalent), at 2.5 GyE per daily fraction, was well tolerated in patients who were previously treated for NPC with a definitive dose of IMXT. The short-term response rates at 3-6 months were also acceptable. However, no patients were treated with concurrent chemotherapy. Whether the addition of concurrent chemotherapy to CIRT can benefit locally recurrent NPC patients over CIRT alone has never been addressed. It is possible that the benefits of high-LET CIRT may make radiosensitizing chemotherapy unnecessary. We therefore implemented a phase I/II clinical trial to address these questions and present our methodology and results. The maximal tolerated dose (MTD) of re-treatment using raster

  18. Effects of salvage logging and pile-and-burn on fuel loading, potential fire behaviour, fuel consumption and emissions

    Treesearch

    Morris C. Johnson; Jessica E. Halofsky; David L. Peterson

    2013-01-01

    We used a combination of field measurements and simulation modelling to quantify the effects of salvage logging, and a combination of salvage logging and pile-and-burn fuel surface fuel treatment (treatment combination), on fuel loadings, fire behaviour, fuel consumption and pollutant emissions at three points in time: post-windstorm (before salvage logging), post-...

  19. Fine targeting of purine salvage in Cryptosporidium parasites.

    PubMed

    Hyde, John E

    2008-08-01

    The apicomplexan pathogen Cryptosporidium parvum poses major logistical problems in the search for effective drug treatments. These treatments are required urgently because this parasite can cause severe disease and death in immunocompromised individuals and young children. In a recent study, the dependence of Cryptosporidium parasites on a single salvage pathway that leads to essential purine derivatives has been exploited and inhibitors have been identified that selectively target a key enzyme in this salvage process, inosine 5'-monophosphate dehydrogenase.

  20. Neutropenia as a prognostic factor and safety of second-line therapy with S-1 for advanced or recurrent pancreatic cancer.

    PubMed

    Ikagawa, Makiko; Kimura, Michio; Iwai, Mina; Usami, Eiseki; Yoshimura, Tomoaki; Yasuda, Kimio

    2016-09-01

    The aim of this retrospective study was to investigate the safety of S-1 as second-line therapy and to evaluate the association between neutropenia occurring during first-line gemcitabine (GEM) therapy and survival for advanced or recurrent pancreatic cancer (APC). Between January, 2010 and December, 2014, 123 APC patients received chemotherapy at the Ogaki Municipal Hospital (Ogaki, Japan). Of those, 37 received GEM as first-line and S-1 as a second-line therapy (GEM→S-1 group). A further 60 patients received GEM as first-line therapy, but did not receive second-line therapy (GEM group). The median overall survival in the GEM→S-1 (n=37) and GEM (n=60) groups was 323 days [95% confidence interval (CI): 138-218.9 days] and 172 days (95% CI: 105-184.4 days), respectively (P=0.0004). The median overall survival in the mild (grade ≤2; n=63) and severe (grade ≥3; n=34) neutropenia groups was 178 days (95% CI: 182-275 days) and 330 days (95% CI: 297-514 days), respectively (log-rank test, P=0.0023). The severe non-haematological toxicities associated with S-1 as second-line therapy were nausea (2.7%) and hand-foot syndrome (2.7%). Second-line S-1 treatment was discontinued due to adverse events in 5.4% (2/37) of the cases. In conclusion, neutropenia occurring during GEM therapy administered as first-line treatment to APC patients was strongly associated with a better prognosis. S-1 therapy as second-line treatment was associated with a low incidence of severe adverse events and the patients were able to successfully continue treatment.

  1. Salvage treatment with temozolomide in refractory or relapsed primary central nervous system lymphoma and assessment of the MGMT status.

    PubMed

    Makino, Keishi; Nakamura, Hideo; Hide, Taku-Ichiro; Kuratsu, Jun-Ichi

    2012-01-01

    High-dose methotrexate (HD-MTX) is effective in the initial treatment of primary central nervous system lymphoma (PCNSL). Because treatment options in patients with progressive or recurrent PCNSL are limited, prognosis is poor. Temozolomide, a well-tolerated oral alkylating agent that permeates the blood brain barrier (BBB), is effective against malignant glioma and recurrent PCNSL. The gene for the deoxyribonucleic acid (DNA) repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT), which is closely related to cellular sensitivity to alkylating agents, is inactivated by promoter hypermethylation. We evaluated the results of temozolomide treatment and the methylation status of the promoter region of the MGMT gene in 17 patients (median age 68 years) with refractory or relapsed PCNSL. They were immunocompetent and had received initial treatment with HD-MTX (3.5 g/m(2)) with or without irradiation. All were treated with temozolomide 150-200 mg/m(2), for 5 days in the course of 28 days; treatment was continued until disease progression. We observed five complete remissions, five partial responses (PRs) with stable disease (SD), and seven with disease progression. Median overall survival after the temozolomide treatment was 6.7 months. One patient manifested grade 3 neutropenia and thrombocytopenia. Eleven tumor specimens were available for MGMT analysis. MGMT promoter methylation (mMGMT) in the tumor tissue was found in 4 (36.4%), the other seven harbored a non-methylated MGMT promoter (nmMGMT). There was no statistically significant difference in median overall survival between patients with mMGMT (11.1 months) and nmMGMT (6.7 months) (P = 0.63). Although some patients were elderly and had been heavily pre-treated, temozolomide resulted in a complete response (CR) in 29% and was well tolerated without any major toxicity.

  2. Contribution of Moxifloxacin or Levofloxacin in Second-Line Regimens with or without Continuation of Pyrazinamide in Murine Tuberculosis

    PubMed Central

    Ahmad, Zahoor; Tyagi, Sandeep; Minkowski, Austin; Peloquin, Charles A.; Grosset, Jacques H.

    2013-01-01

    Rationale: High-dose levofloxacin (L) (1,000 mg) was as active as moxifloxacin (M) (400 mg) in an early bactericidal activity trial, suggesting these fluoroquinolones could be used interchangeably. Whether pyrazinamide (Z) contributes sterilizing activity beyond the first 2 months in fluoroquinolone-containing second-line regimens remains unknown. Objectives: We compared the efficacy of M and high-dose L alone or in combination with ethionamide (Et), amikacin (A), and Z given for 2 or 7 months. Methods: A pharmacokinetic study was performed to determine the L dose equivalent to 1,000 mg in humans. Treatment started 2 weeks after aerosol infection with Mycobacterium tuberculosis H37Rv. Mice received M or L alone or in combination with 2 months of EtZA followed by 5 months of Et or EtZ. Measurements and Main Results: After 2 months of treatment, lung colony-forming unit (CFU) counts were similar in mice receiving either fluoroquinolone alone, but, after 4 and 5 months, CFU counts were 2 log10 lower in mice receiving M. Mice receiving 2MEtZA/3MEt and 2LEtZA/3LEt had 1.0 and 2.7 log10 lung CFUs, respectively. When Z was given throughout, both regimens rendered mice culture negative by 5 months, and most mice did not relapse after 7 months of treatment, with fewer relapses observed in the M group after 6 and 7 months of treatment. Conclusions: In murine tuberculosis, M had superior efficacy compared with L despite lower serum drug exposures and may remain the fluoroquinolone of choice for second-line regimens. Z contributed substantial sterilizing activity beyond 2 months in fluoroquinolone-containing second-line regimens, largely compensating for L’s weaker activity. PMID:23593945

  3. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

    PubMed Central

    von Felden, Johann; Schulze, Kornelius; Gil-Ibanez, Ines; Werner, Tobias; Wege, Henning

    2016-01-01

    Advanced hepatocellular carcinoma (HCC) with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC) classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI) sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) is helpful to identify patients who do not benefit from sorafenib treatment. PMID:27916795

  4. Comparison of Second-Line Quadruple Therapies with or without Bismuth for Helicobacter pylori Infection.

    PubMed

    Jheng, Guang-Hong; Wu, I-Chen; Shih, Hsiang-Yao; Wu, Meng-Chieh; Kuo, Fu-Chen; Hu, Huang-Ming; Liu, Chung-Jung; Hsu, Wen-Hung; Hu, Chi-Tan; Bair, Ming-Jong; Kuo, Chao-Hung; Wu, Deng-Chyang; Hsu, Ping-I

    2015-01-01

    The bismuth-based quadruple regimen has been applied in Helicobacter pylori rescue therapy worldwide. The non-bismuth-based quadruple therapy or "concomitant therapy" is an alternative option in first-line eradication but has not been used in second-line therapy. Discovering a valid regimen for rescue therapy in bismuth-unavailable countries is important. We conducted a randomized controlled trial to compare the efficacies of the standard quadruple therapy and a modified concomitant regimen. One hundred and twenty-four patients were randomly assigned into two groups: RBTM (rabeprozole 20 mg bid., bismuth subcitrate 120 mg qid, tetracycline 500 mg qid, and metronidazole 250 mg qid) and RATM (rabeprozole 20 mg bid., amoxicillin 1 g bid., tetracycline 500 mg qid, and metronidazole 250 mg qid) for 10 days. The eradication rate of the RBTM and RATM regimen was 92.1% and 90.2%, respectively, in intention-to-treat analysis. Patients in both groups had good compliance (~96%). The overall incidence of adverse events was higher in the RATM group (42.6% versus 22.2%, P = 0.02), but only seven patients (11.5%) experienced grades 2-3 events. In conclusion, both regimens had good efficacy, compliance, and acceptable side effects. The 10-day RATM treatment could be an alternative rescue therapy in bismuth-unavailable countries.

  5. Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer.

    PubMed

    Eisen, Tim; Thatcher, Nick; Leyvraz, Serge; Miller, Wilson H; Couture, Felix; Lorigan, Paul; Lüthi, François; Small, David; Tanovic, Adnan; O'Brien, Mary

    2009-04-01

    To evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy. This was a multicenter, open-label, single-arm, exploratory, phase II clinical trial. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST). The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. Twenty pretreated SCLC patients (median age, 60 years) with extensive (n = 13) or limited-stage disease (n = 7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2). Objective tumor responses were not observed and only one of the 17 evaluable patients had SD. With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively. The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase. This clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC. One patient died due to multi-organ failure. The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.

  6. Treatment, rationale, and study design of TALISMAN study: a randomized phase II open-label study of second-line erlotinib versus intermittent erlotinib dosing with docetaxel in the treatment of former-smoker men affected by recurrent squamous non-small-cell lung cancer.

    PubMed

    Gridelli, Cesare; Rossi, Antonio; Venturino, Paola; de Marinis, Filippo

    2011-01-01

    We present the treatment rationale and study design of the TALISMAN (TArceva and docetaxeL In former-Smokers MAle patients with recurrent Non-small-cell lung cancer) study, an open-label, randomized phase II trial of erlotinib (arm A) or intermittent erlotinib and docetaxel (arm B) in male former smokers affected by recurrent squamous non-small-cell lung cancer (NSCLC). In arm A, treatment consists of erlotinib 150 mg daily orally until progression or inacceptable toxicity; in arm B, treatment consists of docetaxel 75 mg/m² on day 1 and erlotinib 150 mg orally on days 2-16, recycled every 3 weeks up to 4 cycles followed, in patients not progressed, by erlotinib 150 mg daily orally until disease progression or inacceptable toxicity. The primary endpoint of this study is the rate of patients without progression at 6 months, and secondary objectives include median progression-free survival, median overall survival, activity, and toxicity. In addition, translational research evaluating EGFR and KRAS mutational status will be investigated for both arms.

  7. 26 CFR 1.832-7T - Treatment of salvage and reinsurance in computing “losses incurred” deduction, taxable years...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...). (a) In computing “losses incurred” the determination of unpaid losses at the close of each year must... includes all property (other than cash), real or personal, tangible or intangible, except that which may.... Such salvage in course of liquidation shall be taken into account to the extent of the value thereof at...

  8. Effects of post-fire salvage logging and a skid trail treatment on ground cover, soils, and sediment production in the interior western United States

    Treesearch

    Joseph W. Wagenbrenner; Lee H. MacDonald; Robert N. Coats; Peter R. Robichaud; Robert E. Brown

    2015-01-01

    Post-fire salvage logging adds another set of environmental effects to recently burned areas, and previous studies have reported varying impacts on vegetation, soil disturbance, and sediment production with limited data on the underlying processes. Our objectives were to determine how: (1) ground-based post-fire logging affects surface cover, soil water repellency,...

  9. Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

    PubMed Central

    Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J.

    2016-01-01

    Background: Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC

  10. Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma.

    PubMed

    Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J

    2016-01-01

    Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC, carbon ion

  11. Second line palliative endobronchial radiotherapy with HDR Ir 192 in recurrent lung carcinoma.

    PubMed

    Zorlu, A Faruk; Selek, Ugur; Emri, Salih; Gurkaynak, Murat; Akyol, Fadil H

    2008-08-30

    To observe the efficiency of reirradiation with high dose rate intraluminal brachytherapy in symptomatic palliation of recurrent endobronchial tumors. Between January 1994 and June 1998, 21 patients diagnosed with recurrent endobronchial tumors following external beam radiotherapy were treated palliatively with high dose rate intraluminal irradiation at Hacettepe University Oncology Institute. A single fraction of 10 Gy was prescribed to the specified area in 9 patients and 15 Gy to 12. Endobronchial treatment improved the performance and reduced symptomatology in 17 (81%) patients. Ten dyspneic patients (10/14, 71%) recovered clinically with an accompanying radiological downstaging. The median symptomatic palliation was 45 days (range, 0-9 months), and the overall median survival was 5.5 months (range, 4-12 months). The palliative intrabronchial brachytherapy was well tolerated, with the exception of in one patient with a fatal hemorrhage, and another with medically salvaged bronchospasm and intrabronchial edema. Recurrent patients with a history of previous thoracic external beam irradiation can be effectively palliated with high dose rate endobronchial reirradiation if the symptoms are directly related to the endobronchial tumor.

  12. Local salvage therapy for late (≥2 years) metastatic and local relapse of renal cell cancer is a potentially curative treatment irrespective of the site of recurrence.

    PubMed

    Grüllich, Carsten; Vallet, Sonia; Hecht, Christopher; Duensing, Stephan; Hadaschik, Boris; Jäger, Dirk; Hohenfellner, Markus; Pahernik, Sascha

    2016-05-01

    The primary treatment approach to locoregional renal cell carcinoma (RCC) is surgical resection. Most relapses occur within the first 2 years but some patients experience late recurrences. Surgical resection of oligometastatic disease may be considered a curative option for relapsed RCC. However, limited data are available of long-term follow-up of late relapse regarding treatment choice. We identified 104 patients with RCC from our database, who relapsed after≥2 years from resection of their primary tumor. Median age at primary diagnosis was 61 years and sex distribution was F:M = 40:64. Histology was clear cell, n = 103 and papillary, n = 1. Sites of relapse were local, n = 14 (13.4%); lung only, n = 25 (24.0%); or extrapulmonary, n = 65 (62.5%). Treatment at first relapse was local therapy (LT) in n = 60 (57.7%) patients, of these, n = 55 patients had surgery done and n = 5 patients had underwent radiotherapy. Systemic therapy was used in n = 9 (8.7%) patients. Overall, 35 patients received best supportive care (33.7%). We found a median overall survival (OS) of 49.8 months (95% CI: 29.3-70.2) and a progression-free survival (PFS) of 21.6 months (95% CI: 12.6-30.5) for all patients. Patients receiving LT had a median OS of 99.9 months (95% CI: 77.2-122.6) and a PFS of 31.1 months (95% CI: 21.5-40.7). Patients treated with systemic therapy, in turn, had an OS of 21.1 months (95% CI: 8.4-33.8) and a PFS of 4 months (95% CI: 1.0-6.2). Patients who received best supportive care had an OS of 10 months (95% CI: 1.3-18.7). This difference was highly significant (log rank for PFS: P<0.001; log rank for OS: P<0.003). Subgroup analysis of the LT group showed a superior outcome for local relapses (OS: not reached, PFS: 61.4mo [95% CI: 28.5-9.2]) compared to visceral relapses (OS: 35.5mo [95% CI: 17.9-53.1], PFS: 21.1mo [95% CI: 19.2-22.9]). Local salvage therapy should be considered the first therapeutic option in late relapse of RCC irrespective of the site of relapse

  13. Dexa-BEAM as salvage therapy in patients with primary refractory aggressive non-Hodgkin lymphoma.

    PubMed

    Atta, Johannes; Chow, Kai U; Weidmann, Eckhart; Mitrou, Paris S; Hoelzer, Dieter; Martin, Hans

    2007-02-01

    Although aggressive NHL in relapse after remission can still be cured by second-line treatment followed by high-dose therapy and autologous stem cell transplantation, the long-term prognosis of patients who fail to obtain remission after first-line therapy remains extremely poor. We retrospectively evaluated a series of 29 consecutive patients with primary refractory high-grade NHL who were treated with Dexa-BEAM (DB) as uniform salvage therapy at a single institution. Twenty-nine patients with aggressive NHL primary refractory to CHOP or CHOP-like induction therapy with a median age of 47 (range, 22 - 64) years received 1 - 2 cycles of DB and were candidates for subsequent autologous stem cell (PBSC) mobilization and transplantation (PBSCT). Follow-up of all patients was updated in March 2004. Eight of 29 patients (28%) responded to one cycle of DB (1 complete/7 partial remissions); 2 of whom are alive after PBSCT (1 autologous/1 matched unrelated donor), 1 patient died after autologous PBSCT. Reasons for failure to proceed to high-dose therapy in spite of response to DB were recurrent progressive disease (n = 2), septicemia (n = 1), and allogeneic transplant-related mortality after mobilization failure to DB (n = 2). Twenty-one patients failed to respond to DB and died of progressive disease. Overall survival was 7% after 41 months. We conclude that Dexa-BEAM salvage therapy is not effective in patients with truly primary refractory high-grade NHL. The efficiency of rituximab combined with Dexa-BEAM or novel chemotherapeutic strategies needs to be established.

  14. Salvage radiotherapy in prostate cancer patients. Planning, treatment response and prognosis using (11)C-choline PET/CT.

    PubMed

    García, J R; Cozar, M; Soler, M; Bassa, P; Riera, E; Ferrer, J

    2016-01-01

    To assess the prognostic value of the therapeutic response by (11)C-choline PET/CT in prostate cancer patients with biochemical recurrence in which (11)C-choline PET/CT indicated radio-guided radiotherapy. The study included 37 patients initially treated with prostatectomy, who were treated due to biochemical recurrence. (11)C-choline PE/CT detected infra-diaphragmatic lymph-node involvement. All were selected for intensity modulated radiation therapy, escalating the dose according to the PET findings. One year after treatment patients underwent PSA and (11)C-choline PET/CT categorizing response (complete/partial/progression). Clinical/biochemical/image monitoring was performed until appearance of second relapse or 36 months in disease-free patients. (11)C-choline PET/CT could detect lymph nodes in all 37 patients. They were 18 (48.6%) of more than a centimetre in size and 19 (51.3%) with no pathological CT morphology: 9 (24.3%) with positive lymph nodes of around one centimetre and 10 (27.0%) only less than a centimetre in size. The response by (11)C-choline PET/CT was categorised one year after radiotherapy: 16 patients (43.2%) complete response; 15 (40.5%) partial response, and 6 (16.2%) progression. The response was concordant between the PSA result and (11)C-choline PET/CT in 32 patients (86.5%), and discordant in five (13.5%). New recurrence was detected in 12 patients (80%) with partial response, and 5 (31.2%) with complete response. The mean time to recurrence was 9 months after partial response, and 18 months after complete response (significant difference, p<.0001). (11)C-choline PET/CT allows the selection of patients with recurrent prostate cancer candidates for radiotherapy and to plan the technique. The evaluation of therapeutic response by (11)C-choline PET/CT has prognostic significance. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  15. Apatinib as post second-line therapy in EGFR wild-type and ALK-negative advanced lung adenocarcinoma

    PubMed Central

    Fang, Shen-Cun; Zhang, Hai-Tao; Zhang, Ying-Ming; Xie, Wei-Ping

    2017-01-01

    In the absence of a driver mutation, chemotherapy is the standard treatment option as first- and second-line therapy for advanced non-small-cell lung cancer (NSCLC). Though a large number of patients are suitable for post second-line therapies, the quality and quantity of the available drugs in this setting is poor. Apatinib, a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, is a first-generation oral antiangiogenesis drug approved in the People’s Republic of China for use as a subsequent line of treatment for advanced gastric cancer. Herein, we report three cases of advanced NSCLC with epidermal growth factor receptor wild-type and anaplastic lymphoma kinase-negative status, wherein the patients showed partial response to apatinib. Moreover, the three patients have achieved a progression-free survival of 2.8, 5.8, and 6 months, respectively. The main toxicities were hypertension, proteinuria, and hand–foot syndrome. Apatinib may provide an additional option for the treatment of advanced NSCLC, especially for advanced lung adenocarcinoma without a driver mutation. PMID:28176910

  16. Gemcitabine as second-line chemotherapy after Folfirinox failure in advanced pancreatic adenocarcinoma: A retrospective study.

    PubMed

    Viaud, Juliette; Brac, Clémence; Artru, Pascal; Le Pabic, Estelle; Leconte, Bérengère; Bodère, Anaïs; Pracht, Marc; Le Sourd, Samuel; Edeline, Julien; Lièvre, Astrid

    2017-06-01

    Pancreatic adenocarcinoma (PA) is diagnosed in most cases at an advanced stage requiring chemotherapy. Folfirinox is the standard first-line treatment. After Folfirinox failure, gemcitabine alone is routinely used as second-line therapy without data supporting this attitude. Determine the response rate and outcome of patients with advanced PA treated with gemcitabine after Folfirinox failure. We retrospectively analyzed all consecutive patients treated with gemcitabine after Folfirinox failure for a locally advanced or metastatic PA between 2009 and 2015. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Response rate, control rate and tolerability were assessed. 96 patients were included (male, 51%; median age, 62; performance status (PS) 0-1, 47%). Median duration on gemcitabine was 2.1 months. The overall disease control rate was 40%. Median OS was 3.7 months (95%CI: 2.5-5.2) and median PFS was 2.1 months (95%CI: 2.0-2.6). Reasons for treatment discontinuation were mostly progression (51%). Age at diagnosis and PS were independently associated with OS in multivariate analysis (HR of 1.86; p=0.0055 and 2.42; p<0.0001 respectively). 34 patients experienced a grade 3 adverse event. This study suggests that gemcitabine is not beneficial to all patients failing on Folfirinox first-line therapy and should be restricted to young patients with good PS. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  17. A phase II trial of second-line pemetrexed in adults with advanced/metastatic osteosarcoma.

    PubMed

    Duffaud, Florence; Egerer, Gerlinde; Ferrari, Stefano; Rassam, Hisham; Boecker, Ulrike; Bui-Nguyen, B

    2012-03-01

    Osteosarcoma is the most common primary malignant tumour in young adults. An effective treatment strategy for relapsed patients is still not defined. Pemetrexed is a multitargeted antifolate with a mode of action similar to, and a range of action broader than that of methotrexate. The primary objective of this phase II study was to determine tumour response rate in patients with high-grade, advanced/metastatic osteosarcoma. Secondary end-points included progression-free survival (PFS), overall survival (OS) and safety. Pemetrexed 500mg/m(2) was administered on day 1 of 21-day cycles with folic acid and vitamin B(12) supplementation. At least 5 tumour responses in a targeted population of 32 were required to consider further investigation. Thirty-two patients (median age, 43.3 years; range, 18.6-76.0) with 1 prior chemotherapy regimen for high-grade advanced/metastatic osteosarcoma were enrolled. Thirty (93.8%) patients had an ECOG performance status ≤ 1 and 29 (90.6%) had metastases in the lung. One patient had partial response (3.1%) and 5 (15.6%) had stable disease. Median PFS and OS were 1.4 months (95% CI: 1.4-1.7) and 5.5 months (95% CI: 2.3-10.5), respectively. The most common drug-related grade 3/4 toxicities were leukopaenia, asthaenia and elevated alanine aminotransferase in 3 (9.4%) patients each. One patient died due to multi-organ failure considered possibly related to the study drug. Pemetrexed 500mg/m(2) administered on day 1 of 21-day cycles as second-line treatment to patients with advanced/metastatic high-grade osteosarcoma was generally well tolerated but did not meet minimal response expectations for further investigation in this patient population. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Salvage radioembolization of liver-dominant metastases with a resin-based microsphere: initial outcomes.

    PubMed

    Stuart, Jourdan E; Tan, Benjamin; Myerson, Robert J; Garcia-Ramirez, Jose; Goddu, Sreekrishna M; Pilgram, Thomas K; Brown, Daniel B

    2008-10-01

    The use of radioembolization of hepatic metastases with yttrium-90 ((90)Y) microspheres is increasing. The present report describes the outcomes in a cohort of patients with metastatic liver tumors treated with a resin-based microsphere agent. Thirty patients with colon (n = 13), breast (n = 7), and other primary cancers (n = 10) were treated after the failure of first- and second-line therapy. Overall survival (OS), time to progression (TTP), and time to treatment failure (TTTF) were calculated from the first treatment. Response was measured according to Response Evaluation Criteria In Solid Tumors at interval follow-up imaging. Thirty patients underwent 56 infusions of (90)Y, and 18 remained alive at the end of the study. Fourteen patients (47%) had a partial response or stable disease. OS (604 vs 251 days), TTP (223 vs 87 days), and TTTF (363 vs 87 days) were all significantly longer for patients who had a partial response or stable disease (P < .05). Median OS, TTP, and TTTF for patients with colorectal carcinoma were 357, 112, and 107 days, respectively, versus 638, 118, and 363 days in patients with other metastatic sources. Median survival was not reached for patients with breast carcinoma, and the TTP and TTTF were each 282 days. One patient (3%) experienced grade 3 toxicity (gastrointestinal ulceration). (90)Y microsphere therapy produced promising survival rates compared with systemic salvage options, with minimal toxicity.

  19. Novel therapeutic options for second-line therapy in metastatic renal cell carcinoma

    PubMed Central

    VON KLOT, CHRISTOPH-A. J.; MERSEBURGER, AXEL S.; KUCZYK, MARKUS A.

    2016-01-01

    Metastatic renal cell carcinoma (mRCC) has gained a variety of therapeutic options since the introduction of targeted therapy, starting in 2007. The basic molecular mechanisms included predominantly the targeting of vascular endothelial growth factor or the inhibition of the mammalian target of rapamycin. Recently, results from two randomized controlled trials, the CheckMate-25 and the METEOR trial, regarding therapy for RCC in the second-line setting have been published. In the present review, the current status of second-line therapy in mRCC is discussed, together with results from the two newly introduced substances, nivolumab and cabozantinib. PMID:27313856

  20. A comparison of computational models with and without genotyping for prediction of response to second-line HIV therapy.

    PubMed

    Revell, A D; Boyd, M A; Wang, D; Emery, S; Gazzard, B; Reiss, P; van Sighem, A I; Montaner, J S; Lane, H C; Larder, B A

    2014-08-01

    We compared the use of computational models developed with and without HIV genotype vs. genotyping itself to predict effective regimens for patients experiencing first-line virological failure. Two sets of models predicted virological response for 99 three-drug regimens for patients on a failing regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and one nonnucleoside reverse transcriptase inhibitor in the Second-Line study. One set used viral load, CD4 count, genotype, plus treatment history and time to follow-up to make its predictions; the second set did not include genotype. Genotypic sensitivity scores were derived and the ranking of the alternative regimens compared with those of the models. The accuracy of the models and that of genotyping as predictors of the virological responses to second-line regimens were compared. The rankings of alternative regimens by the two sets of models were significantly correlated in 60-69% of cases, and the rankings by the models that use a genotype and genotyping itself were significantly correlated in 60% of cases. The two sets of models identified alternative regimens that were predicted to be effective in 97% and 100% of cases, respectively. The area under the receiver-operating curve was 0.72 and 0.74 for the two sets of models, respectively, and significantly lower at 0.55 for genotyping. The two sets of models performed comparably well and significantly outperformed genotyping as predictors of response. The models identified alternative regimens predicted to be effective in almost all cases. It is encouraging that models that do not require a genotype were able to predict responses to common second-line therapies in settings where genotyping is unavailable. © 2014 British HIV Association.

  1. Limb-salvage treatment of en-block resected distal femoral tumors with endoprosthesis of all-polyethylene tibial component: a 9-year follow-up study

    PubMed Central

    Tang, Fan; Zhou, Yong; Min, Li; Zhang, Wenli; Shi, Rui; Luo, Yi; Duan, Hong; Tu, Chongqi

    2016-01-01

    Objective To evaluate the medium-term outcome of limb-salvage surgery using all-polyethylene tibial endoprosthetic replacement following en-block resection for distal femoral tumors. Methods Forty-nine patients with distal femoral tumor were treated between June 2006 and June 2012. The follow-up period was 6–110 months (average 53.4 months). The prosthetic survival was analyzed using the Kaplan–Meier method. The classification of failure of limb salvage after reconstructive surgery for bone tumors was adapted. Limb function was evaluated with the scoring system of the Musculoskeletal Tumor Society (MSTS). Results Complications were observed in six cases (12.2%). Four suffered infection around the prosthesis, of which two cases were treated with debridement, drainage, and antibiotics without removal of the prosthesis, and the other two cases underwent amputation. Two cases were identified as radiographically loose at 7 year follow-up and did not require revision surgery. One patient underwent amputation due to local recurrence. Failure of limb salvage occurred in nine cases (18.4%), of which two cases were of type 1A, two cases of type 2B, three cases of type 4A, one case of type 4B, and one case of type 5A. The mean MSTS score was 84.3%. Twelve cases died due to distant metastases (24.5%), and the average survival time for these patients was 13.5 months. Thirty-seven patients survived (75.5%), for whom the average follow-up time was 66.3 months and the 5-year prosthetic survival rate was 88.2%. Conclusion The outcome of medium-term and long-term clinical follow-up was satisfactory. All-polyethylene tibial endoprosthetic replacement following en-block resection can be an alternative method of limb salvage for distal femoral tumors. PMID:27695342

  2. Efficacy of Immediate Switching from Bicalutamide to Flutamide as Second-Line Combined Androgen Blockade.

    PubMed

    Yokomizo, Yumiko; Kawahara, Takashi; Miyoshi, Yasuhide; Otani, Masako; Yamanaka, Shoji; Teranishi, Jun-Ichi; Noguchi, Kazumi; Yao, Masahiro; Uemura, Hiroji

    2016-01-01

    We determined whether prostate specific antigen (PSA) would decrease with immediate antiandrogen switching from bicalutamide (BCL) to flutamide (FLT) in patients receiving combined androgen blockade for advanced prostate cancer. From 2002 to 2006, 20 patients who showed PSA failure after first-line hormonal therapy with a luteinizing hormone-release hormone (LH-RH) agonist and BCL were enrolled. All patients were immediately switched from BCL to FLT, administered with an LH-RH agonist, as second-line combined androgen blockade (CAB). We evaluated the PSA response to second-line CAB. Eight patients (40%) were responsive, showing PSA decreases of at least 50%. The median (range) duration of the PSA response was 18.4 (3-26) months. Second-line CAB using FLT was effective in 40% of patients who received first-line CAB using BCL. The lower Gleason scores at the initial prostate biopsy probably reflect the response to second-line CAB. Responders showed significantly better OS and CSS in the determination of any PSA decline and 40% PSA decline. The median OS duration in nonresponders and responders (40% PSA decline) was 1433 days versus 3617 days. It is concluded that an immediate switch from BCL to FLT is effective for some CRPC patients after first-line CAB using BCL.

  3. Efficacy of Immediate Switching from Bicalutamide to Flutamide as Second-Line Combined Androgen Blockade

    PubMed Central

    Yokomizo, Yumiko; Kawahara, Takashi; Miyoshi, Yasuhide; Otani, Masako; Yamanaka, Shoji; Teranishi, Jun-ichi; Noguchi, Kazumi; Yao, Masahiro

    2016-01-01

    We determined whether prostate specific antigen (PSA) would decrease with immediate antiandrogen switching from bicalutamide (BCL) to flutamide (FLT) in patients receiving combined androgen blockade for advanced prostate cancer. From 2002 to 2006, 20 patients who showed PSA failure after first-line hormonal therapy with a luteinizing hormone-release hormone (LH-RH) agonist and BCL were enrolled. All patients were immediately switched from BCL to FLT, administered with an LH-RH agonist, as second-line combined androgen blockade (CAB). We evaluated the PSA response to second-line CAB. Eight patients (40%) were responsive, showing PSA decreases of at least 50%. The median (range) duration of the PSA response was 18.4 (3–26) months. Second-line CAB using FLT was effective in 40% of patients who received first-line CAB using BCL. The lower Gleason scores at the initial prostate biopsy probably reflect the response to second-line CAB. Responders showed significantly better OS and CSS in the determination of any PSA decline and 40% PSA decline. The median OS duration in nonresponders and responders (40% PSA decline) was 1433 days versus 3617 days. It is concluded that an immediate switch from BCL to FLT is effective for some CRPC patients after first-line CAB using BCL. PMID:27493956

  4. Second Line of Defense Virtual Private Network Guidance for Deployed and New CAS Systems

    SciTech Connect

    Singh, Surya V.; Thronas, Aaron I.

    2010-01-01

    This paper discusses the importance of remote access via virtual private network (VPN) for the Second Line of Defense (SLD) Central Alarm System (CAS) sites, the requirements for maintaining secure channels while using VPN and implementation requirements for current and future sites.

  5. Comparative Effectiveness of Second-Line Targeted Therapies for Metastatic Renal Cell Carcinoma: A Systematic Review and Meta-Analysis of Real-World Observational Studies.

    PubMed

    Heng, Daniel Y; Signorovitch, James; Swallow, Elyse; Li, Nanxin; Zhong, Yichen; Qin, Paige; Zhuo, Daisy Y; Wang, Xufang; Park, Jinhee; Stergiopoulos, Sotirios; Kollmannsberger, Christian

    2014-01-01

    The optimal sequencing of targeted therapies for metastatic renal cell carcinoma (mRCC) is unknown. Observational studies with a variety of designs have reported differing results. The objective of this study is to systematically summarize and interpret the published real-world evidence comparing sequential treatment for mRCC. A search was conducted in Medline and Embase (2009-2013), and conference proceedings from American Society of Clinical Oncology (ASCO), ASCO Genitourinary Cancers Symposium (ASCO-GU), and European Society for Medical Oncology (ESMO) (2011-2013). We systematically reviewed observational studies comparing second-line mRCC treatment with mammalian target of rapamycin inhibitors (mTORi) versus vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI). Studies were evaluated for 1) use of a retrospective cohort design after initiation of second-line therapy, 2) adjustment for patient characteristics, and 3) use of data from multiple centers. Meta-analyses were conducted for comparisons of overall survival (OS) and progression-free survival (PFS). Ten studies reported OS and exhibited significant heterogeneity in estimated second-line treatment effects (I2 = 68%; P = 0.001). Four of these were adjusted, multicenter, retrospective cohort studies, and these showed no evidence of heterogeneity (I2 = 0%; P = 0.61) and a significant association between second-line mTORi (>75% everolimus) and longer OS compared to VEGF TKI (>60% sorafenib) (HR = 0.82, 95% CI: 0.68 to 0.98) in a meta-analysis. Seven studies comparing PFS showed significant heterogeneity overall and among the adjusted, multicenter, retrospective cohort studies. Real-world observational data for axitinib outcomes was limited at the time of this study. Real-world studies employed different designs and reported heterogeneous results comparing the effectiveness of second-line mTORi and VEGF TKI in the treatment of mRCC. Within the subset of adjusted

  6. One-week quadruple therapy is an effective salvage regimen for Helicobacter pylori infection in patients after failure of standard triple therapy.

    PubMed

    Lin, Chiun-Ku; Hsu, Ping-I; Lai, Kwok-Hung; Lo, Gin-Ho; Tseng, Hui-Hwa; Lo, Ching-Chu; Peng, Nan-Jing; Chen, Hui-Chun; Jou, Huei-Shu; Huang, Wen-Keui; Chen, Jin-Liang; Hsu, Ping-Ning

    2002-01-01

    Standard triple therapy remains an important option for eradicating Helicobacter pylori (Hp) in developing countries because of its relatively low cost. However, salvage therapies after failure of this regimen remain undefined. The authors therefore investigate the efficacy of 1-week quadruple therapy as a second-line treatment of Hp infection after failure of standard triple therapy. Seventy-eight patients who failed Hp eradication using a 2-week bismuth-based triple therapy were enrolled and received a course of 1-week quadruple therapy (lansoprazole, 30 mg twice daily; bismuth subcitrate, 120 mg four times daily; clarithromycin, 500 mg twice daily; and amoxicillin, 1,000 mg twice daily) as a salvage regimen. The Hp status was reassessed 7 weeks after cessation of therapy. Among the 78 patients, Hp eradication was achieved in 65 (83%, 95% confidence interval = 75-91%) by intention-to-treat analysis. Only five (6%) patients had side effects, and all (100%) showed good drug compliance. Multivariate analysis disclosed that coffee drinking was an independent factor for treatment failure (odds ratio = 5.3, 95% confidence interval = 1.2-23.6, p = 0.028). The authors therefore conclude that their 1-week quadruple therapy is an effective salvage regimen for Hp infection after failure of standard triple therapy in the population examined. The benefits of this regimen include the high eradication rate, the short duration of treatment, fewer side effects, and good drug compliance. Coffee consumption possibly is an important factor in failure of the rescue regimen. The mechanisms underlying the association between coffee drinking and eradication failure require further research.

  7. Endovascular revascularization and free tissue transfer for lower limb salvage.

    PubMed

    Huang, Chieh-Chi; Chang, Chien-Hwa; Hsu, Honda; Mark Chiu, Chih-Hung; Lin, Chih-Ming; Lee, Jiunn-Tat; Chien, Sou-Hsin

    2014-10-01

    Combined bypass surgery with free flap reconstruction is an established method for lower limb salvage. But the success of the combination of endovascular revascularization together with free tissue transfer has so far not been well established. A retrospective review of all patients who had undergone endovascular revascularization and reconstructed with free tissue transfer for lower limb salvage at Tzu Chi Dalin General Hospital between 2008 and 2012 was performed. A total of 26 legs underwent limb salvage in 24 patients. There were 10 male and 14 female patients. Their average age was 71.4 years. The average time interval between endovascular intervention and free tissue transfer was 8 days. There was 100% flap survival but partial flap necrosis was seen in three patients. A high rate of wound infection was seen in eight patients, all requiring further debridement. The total limb salvage rate at 1-year follow-up was 96% and 92% at the 2-year follow-up. In conclusion, the success rate of lower limb salvage using a combination of endovascular revascularization and free tissue reconstruction is comparable to using a combination of bypass surgery and free tissue transfer. It is associated with a high flap success rate and a high limb salvage rate. It provides physicians with a further treatment option in the management of ischemic lower limbs with extended tissue loss.

  8. Effects of postfire salvage logging on deadwood-associated beetles.

    PubMed

    Cobb, T P; Morissette, J L; Jacobs, J M; Koivula, M J; Spence, J R; Langor, D W

    2011-02-01

    In Canada and the United States pressure to recoup financial costs of wildfire by harvesting burned timber is increasing, despite insufficient understanding of the ecological consequences of postfire salvage logging. We compared the species richness and composition of deadwood-associated beetle assemblages among undisturbed, recently burned, logged, and salvage-logged, boreal, mixed-wood stands. Species richness was lowest in salvage-logged stands, largely due to a negative effect of harvesting on the occurrence of wood- and bark-boring species. In comparison with undisturbed stands, the combination of wildfire and logging in salvage-logged stands had a greater effect on species composition than either disturbance alone. Strong differences in species composition among stand treatments were linked to differences in quantity and quality (e.g., decay stage) of coarse woody debris. We found that the effects of wildfire and logging on deadwood-associated beetles were synergistic, such that the effects of postfire salvage logging could not be predicted reliably on the basis of data on either disturbance alone. Thus, increases in salvage logging of burned forests may have serious negative consequences for deadwood-associated beetles and their ecological functions in early postfire successional forests.

  9. A national retrospective study of paediatric end-stage liver disease as a predictor of change to second-line therapy in children with autoimmune hepatitis.

    PubMed

    Zizzo, Andréanne N; Jimenez-Rivera, Carolina; Kim, Joseph; Schreiber, Richard A; Ling, Simon C; Yap, Jason; Critch, Jeff; Ahmed, Najma; Alvarez, Fernando; Kamath, Binita M

    2017-10-01

    Adult studies of autoimmune hepatitis (AIH) have shown that the model of end-stage liver disease is associated with resistance to first-line treatment. Using a multicentre retrospective database, we sought to determine if the paediatric end-stage liver disease (PELD) score would similarly predict treatment resistance in paediatric AIH. One hundred and seventy-one children from 13 Canadian centres who fulfilled the International Autoimmune Hepatitis Group (IAIHG) criteria were included and assessed for change to second-line therapy within 24 months of primary treatment onset. Those with PSC overlap at presentation, or missing data on the PELD variables were excluded. PELD was calculated for all remaining patients. Univariate analysis and receiver-operator characteristic (ROC) curves were performed to determine the predictive ability of the PELD score to change to second-line therapy. A total of 103 children were included with median age of 11 years (range 2-17). Mean PELD was -2.51±8.58. Second-line therapy was used within 24 months of diagnosis in 13 patients. Univariate analysis revealed that change to second-line therapy was associated with higher PELD (P=.028) and internal normalized ratio (INR) (P=.011). ROC curves for PELD and its individual components were performed. The strength of association was strongest with INR (AUC 0.72; CI: 0.58-0.86) although the composite PELD score also showed some predictive ability (AUC 0.67; CI: 0.52-0.81). In this paediatric AIH cohort, higher PELD at presentation predicted change to second-line therapy within the first 2 years of follow-up. INR appeared to be the main contributor to that association. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

    PubMed

    Ploussard, Guillaume; Staerman, Frédéric; Pierrevelcin, Jean; Larue, Sébastien; Villers, Arnauld; Ouzzane, Adil; Bastide, Cyrille; Gaschignard, Nicolas; Buge, François; Pfister, Christian; Bonniol, Romain; Rebillard, Xavier; Fadli, Saad; Mottet, Nicolas; Saint, Fabien; Saad, Rodrigue; Beauval, Jean-Baptiste; Roupret, Morgan; Audenet, François; Peyromaure, Mickaël; Delongchamps, Nicolas Barry; Vincendeau, Sébastien; Fardoun, Tarek; Rigaud, Jérôme; Soulie, Michel; Salomon, Laurent

    2014-10-01

    To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

  11. Second-Line Intraperitoneal Chemotherapy for Recurrent Epithelial Ovarian, Tubal and Peritoneal Cancer: A Propensity Score-Matching Study.

    PubMed

    Lu, Chien-Hsing; Chang, Yen-Hou; Lee, Wai-Hou; Chang, Yi; Peng, Chia-Wen; Chuang, Chi-Mu

    2016-01-01

    The superiority of frontline intraperitoneal (IP) over intravenous (IV) chemotherapy is well established in the treatment of epithelial ovarian cancer. However, the role of IP chemotherapy in the second-line setting has rarely been investigated. Consecutive patients diagnosed with recurrent epithelial, tubal and peritoneal cancers between January 2000 and December 2012 were recruited using a propensity score-matching technique to adjust relevant risk factors. In total, 310 patients were included in the final analysis (94 for platinum-refractory/resistant disease and 216 for platinum-sensitive disease). IP chemotherapy demonstrated significantly longer median progression-free survival than IV chemotherapy (4.9 vs. 2.4 months, p < 0.001, for platinum-refractory/resistant disease, and 9.8 vs. 6.9 months, p < 0.001, for platinum-sensitive disease). Second-line IP chemotherapy confers longer progression-free survival than IV chemotherapy. Large-scale clinical trials should be conducted to validate the true efficacy. © 2016 S. Karger AG, Basel.

  12. Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion.

    PubMed

    Virgo, Katherine S; Basch, Ethan; Loblaw, D Andrew; Oliver, Thomas K; Rumble, R Bryan; Carducci, Michael A; Nordquist, Luke; Taplin, Mary-Ellen; Winquist, Eric; Singer, Eric A

    2017-06-10

    Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies. However, guidelines have neither addressed second-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the chemotherapy-naïve population. Recent Data Six phase III randomized controlled trials and expert consensus opinion inform this PCO. Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely. Second-line hormonal therapy (eg, antiandrogens, CYP17 inhibitors) may be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate-specific antigen doubling time or velocity) but otherwise is not suggested. In patients with radiographic evidence of metastases and minimal symptoms, enzalutamide or abiraterone plus prednisone should be offered after discussion with patients about potential harms, benefits, costs, and patient preferences. Radium-223 and sipuleucel-T also are options. No evidence provides guidance about the optimal order of hormonal therapies for CRPC beyond second-line treatment. Prostate-specific antigen testing every 4 to 6 months is reasonable for men without metastases. Routine radiographic restaging generally is not suggested but can be considered for patients at risk for metastases or who exhibit symptoms or other evidence of progression. Additional information is available at www.asco.org/genitourinary-cancer-guidelines and www.asco.org/guidelineswiki .

  13. Immunological failure of first-line and switch to second-line antiretroviral therapy among HIV-infected persons in Tanzania: analysis of routinely collected national data.

    PubMed

    Vanobberghen, Fiona M; Kilama, Bonita; Wringe, Alison; Ramadhani, Angela; Zaba, Basia; Mmbando, Donan; Todd, Jim

    2015-07-01

    Rates of first-line treatment failure and switches to second-line therapy are key indicators for national HIV programmes. We assessed immunological treatment failure defined by WHO criteria in the Tanzanian national HIV programme. We included adults initiating first-line therapy in 2004-2011 with a pre-treatment CD4 count, and ≥6-months of follow-up. We assessed subhazard ratios (SHR) for immunological treatment failure, and subsequent switch to second-line therapy, using competing risks methods to account for deaths. Of 121 308 adults, 7% experienced immunological treatment failure, and 2% died without observed immunological treatment failure, over a median 1.7 years. The 6-year cumulative probability of immunological treatment failure was 19.0% (95% CI 18.5, 19.7) and of death, 5.1% (4.8, 5.4). Immunological treatment failure predictors included earlier year of treatment initiation (P < 0.001), initiation in lower level facilities (SHR = 2.23 [2.03, 2.45] for dispensaries vs. hospitals), being male (1.27 [1.19, 1.33]) and initiation at low or high CD4 counts (for example, 1.78 [1.65, 1.92] and 5.33 [4.65, 6.10] for <50 and ≥500 vs. 200-349 cells/mm(3) , respectively). Of 7382 participants in the time-to-switch analysis, 6% switched and 5% died before switching. Four years after immunological treatment failure, the cumulative probability of switching was 7.3% (6.6, 8.0) and of death, 6.8% (6.0, 7.6). Those who immunologically failed in dispensaries, health centres and government facilities were least likely to switch. Immunological treatment failure rates and unmet need for second-line therapy are high in Tanzania; virological monitoring, at least for persons with immunological treatment failure, is required to minimise unnecessary switches to second-line therapy. Lower level government health facilities need more support to reduce treatment failure rates and improve second-line therapy uptake to sustain the benefits of increased coverage. © 2015 The

  14. Canadian Multicenter Laboratory Study for Standardized Second-Line Antimicrobial Susceptibility Testing of Mycobacterium tuberculosis ▿

    PubMed Central

    Sharma, Meenu; Thibert, Louise; Chedore, Pamela; Shandro, Cary; Jamieson, Frances; Tyrrell, Gregory; Christianson, Sara; Soualhine, Hafid; Wolfe, Joyce

    2011-01-01

    The purpose of this study was to establish a standardized protocol for second-line antimicrobial susceptibility testing of Mycobacterium tuberculosis using the Bactec MGIT 960 system in Canadian laboratories. Four Canadian public health laboratories compared the susceptibility testing results of 9 second-line antimicrobials between the Bactec 460 and Bactec MGIT 960 systems. Based on the data generated, we have established that the Bactec MGIT 960 system provides results comparable to those obtained with the previous Bactec 460 method. The critical concentrations established for the testing of the antimicrobials used are as follows: amikacin, 1 μg/ml; capreomycin, 2.5 μg/ml; ethionamide, 5 μg/ml; kanamycin, 2.5 μg/ml; linezolid, 1 μg/ml; moxifloxacin, 0.25 μg/ml; ofloxacin, 2 μg/ml; p-aminosalicylic acid, 4 μg/ml; rifabutin, 0.5 μg/ml. PMID:21998413

  15. Canadian multicenter laboratory study for standardized second-line antimicrobial susceptibility testing of Mycobacterium tuberculosis.

    PubMed

    Sharma, Meenu; Thibert, Louise; Chedore, Pamela; Shandro, Cary; Jamieson, Frances; Tyrrell, Gregory; Christianson, Sara; Soualhine, Hafid; Wolfe, Joyce

    2011-12-01

    The purpose of this study was to establish a standardized protocol for second-line antimicrobial susceptibility testing of Mycobacterium tuberculosis using the Bactec MGIT 960 system in Canadian laboratories. Four Canadian public health laboratories compared the susceptibility testing results of 9 second-line antimicrobials between the Bactec 460 and Bactec MGIT 960 systems. Based on the data generated, we have established that the Bactec MGIT 960 system provides results comparable to those obtained with the previous Bactec 460 method. The critical concentrations established for the testing of the antimicrobials used are as follows: amikacin, 1 μg/ml; capreomycin, 2.5 μg/ml; ethionamide, 5 μg/ml; kanamycin, 2.5 μg/ml; linezolid, 1 μg/ml; moxifloxacin, 0.25 μg/ml; ofloxacin, 2 μg/ml; p-aminosalicylic acid, 4 μg/ml; rifabutin, 0.5 μg/ml.

  16. First and second line mechanisms of cadmium detoxification in the lichen photobiont Trebouxia impressa (Chlorophyta).

    PubMed

    Sanità di Toppi, L; Pawlik-Skowrońska, B; Vurro, E; Vattuone, Z; Kalinowska, R; Restivo, F M; Musetti, R; Skowroński, T

    2008-01-01

    "First line" defence mechanisms, such as phytochelatin biosynthesis, and "second line" mechanisms, such as stress protein induction, were investigated in cadmium-exposed cells of Trebouxia impressa Ahmadjian, a green microalgal species that is a common photobiont of the lichen Physcia adscendens (Fr.) H. Olivier. When T. impressa cells were exposed to 0, 9 and 18 microM Cd for 6, 18 and 48 h, glutathione and phytochelatins efficiently protected the cells against Cd damage. By contrast, the highest Cd concentration (36 microM) at the longest exposure-time (48 h) caused marked drops in glutathione and phytochelatin content, several types of ultrastructural damage, and decreases in cell density and total chlorophyll concentration. In this case, induction of stress proteins was observed, but only long after the induction of phytochelatins. Thus, stress proteins could represent a "second line" mechanism to counteract Cd stress, activated when there is a decline in the "first line" mechanism of Cd detoxification given by phytochelatins.

  17. Second-line chemotherapy for patients with advanced gastric cancer: who may benefit?

    PubMed Central

    Catalano, V; Graziano, F; Santini, D; D'Emidio, S; Baldelli, A M; Rossi, D; Vincenzi, B; Giordani, P; Alessandroni, P; Testa, E; Tonini, G; Catalano, G

    2008-01-01

    No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20–40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16–2.77; P=0.008), haemoglobin ⩽11.5 g l−1 (HR, 1.48; 95% CI, 1.06–2.05; P=0.019), CEA level >50 ng ml−1 (HR, 1.86; 95% CI, 1.21–2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16–2.53; P=0.006), and time-to-progression under first-line chemotherapy ⩽6 months (HR, 1.97; 95% CI, 1.39–2.80; P<0.0001). A prognostic index was constructed dividing patients into low- (no risk factor), intermediate- (one to two risk factors), or high- (three to five risk factors) risk groups, and median survival times for each group were 12.7 months, 7.1 months, and 3.3 months, respectively (P<0.001). In the absence of data deriving from randomised trials, this analysis suggests that some easily available clinical factors may help to select patients with advanced gastric cancer who could derive more benefit from second-line chemotherapy. PMID:18971936

  18. Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial.

    PubMed

    Neal, Joel W; Dahlberg, Suzanne E; Wakelee, Heather A; Aisner, Seena C; Bowden, Michaela; Huang, Ying; Carbone, David P; Gerstner, Gregory J; Lerner, Rachel E; Rubin, Jerome L; Owonikoko, Taofeek K; Stella, Philip J; Steen, Preston D; Khalid, Ahmed Ali; Ramalingam, Suresh S

    2016-12-01

    Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC. This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954. Between Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the

  19. A retrospective analysis of efficacy and safety of adding bevacizumab to chemotherapy as first- and second-line therapy in advanced non-small-cell lung cancer (NSCLC).

    PubMed

    Quan, Rencui; Huang, Jiaxing; Chen, Nan; Fang, Wenfeng; Hu, Zhihuang; Zhan, Jianhua; Zhou, Ting; Zhang, Li; Zhang, Hongyu

    2016-08-01

    Several phase III clinical trials had authenticated that the addition of bevacizumab to paclitaxel plus carboplatin or gemcitabine plus cisplatin showed encouraging efficacy as first-line therapy for advanced NSCLC patients. However, the benefits of adding bevacizumab to other chemotherapy regimens in first- or second-line therapy have not been reported. To compare the clinical efficacy and safety of bevacizumab concomitant with chemotherapy regimens in patients with advanced NSCLC as first- or second-line therapy, we retrospectively reviewed the effects of adding bevacizumab to chemotherapy regimens in naive-chemotherapy and pre-chemotherapy patients with advanced non-squamous NSCLC. A total of 79 patients with advanced non-squamous NSCLC received at least two cycles of bevacizumab with chemotherapy between October 2010 and December 2013 were selected. Our primary end points were overall response rate (ORR) and disease control rate (DCR). The secondary objective was overall survival (OS) and safety. Seventy-nine patients were included in this study. Overall response rates at first evaluation (after 2 cycles) were 23.1 % (9/39) and 5.0 % (2/40) in first- and second-line therapy (P = 0.020), respectively. And disease control rates were 84.6 % (33/39) and 50 % (20/40), respectively (P = 0.001). The median OS were 27.2 months (95 % CI 13.3-41.1 months) and 29.6 months (95 % CI 6.7-52.5 months), respectively (P = 0.740). Grade 3-4 adverse events included leukopenia (2/39), and neutropenia (3/39) in first-line therapy versus neutropenia (1/40) and thrombocytopenia (2/40) in second-line treatment. In our experience, combination of bevacizumab and chemotherapy had encouraging anti-tumor efficacy as both first- and second-line therapy.

  20. Evaluation of the MTBDRsl test for detection of second-line-drug resistance in Mycobacterium tuberculosis.

    PubMed

    Kiet, Vo Sy; Lan, Nguyen Thi Ngoc; An, Duong Duy; Dung, Nguyen Huy; Hoa, Dai Viet; van Vinh Chau, Nguyen; Chinh, Nguyen Tran; Farrar, Jeremy; Caws, Maxine

    2010-08-01

    The MTBDRsl assay (Hain Lifescience GmbH, Germany) is a new line probe assay for the detection of extensively drug-resistant tuberculosis (XDR TB). The test simultaneously detects resistance to ethambutol, aminoglycosides/cyclic peptides, and fluoroquinolones through detection of mutations in the relevant genes. The assay format is identical to the MTBDR Hain assay. The assay was evaluated for the detection of second-line-drug resistance in Vietnamese isolates using two sample sets from the microbiology department of Pham Ngoc Thach Hospital, Ho Chi Minh City, Viet Nam, with existing conventional phenotypic drug susceptibility results for second-line drugs: 41 consecutive fluoroquinolone-resistant isolates and 21 consecutive multidrug-resistant but fluoroquinolone-sensitive isolates. The sensitivity for detection of fluoroquinolone resistance was 75.6% (31/41) (95% confidence interval [95% CI], 59.7% to 87.6%), and for kanamycin resistance, the sensitivity was 100% (5/5) (95% CI, 47.8% to 100%). The sensitivity of the test for detection of ethambutol resistance was low, consistent with previous reports, at 64.2% (34/53) (95% CI, 49.8% to 76.9%). The specificity of the test was 100% for all three drugs. These data suggest that the MTBDRsl assay is a rapid, specific test for the detection of XDR TB but should not be used exclusively to "rule out" second-line-drug resistance. Further operational evaluation is required and should be integrated with evaluations of the MTBDR test.

  1. Should phenytoin or barbiturates be used as second-line anticonvulsant therapy for toxicological seizures?

    PubMed

    Shah, Anoop S V; Eddleston, Michael

    2010-10-01

    Seizures are a common sequela of self-poisoning. However, their mechanism differs from seizures of other etiologies. Toxicological seizures result from alterations in the excitatory and inhibitory balance of otherwise normal neurons. In contrast, idiopathic or trauma related seizures usually start with a focus of abnormal neurons. For both forms of seizures, benzodiazepines are recommended as first-line therapy; however, there is debate about the use of phenytoin or barbiturates for second-line therapy. In this article, we systematically review the evidence for the use of these drugs as second-line therapy for toxicological seizures. Barbiturates complement the anticonvulsant effect of benzodiazepines at the GABAA receptor by increasing the duration of chloride channel opening; phenytoin blocks voltage-dependent sodium channels to inhibit propagation from active electrical foci, an effect more useful for nontoxicological seizures. We found no randomized controlled trial comparing phenytoin and barbiturates in toxicological seizures refractory to benzodiazepines; similarly no trial was found comparing the use of these drugs in nonpoisoned patients. Animal studies indicate that phenobarbital has greater effectiveness than phenytoin for many poisons; a few case reports suggest a better response in patients. Despite the lack of high-quality clinical trial data, pharmacological knowledge and animal studies suggest that phenobarbital or thiopentone should be second-line agents for controlling toxicological seizures. The role of newer agents such as propofol and levetiracetam in toxicological seizures is currently unclear because of a lack of clinical or animal studies.

  2. A phase 2 study of fluorouracil/leucovorin in combination with paclitaxel and oxaliplatin as a salvage treatment in patients with refractory or relapsed advanced gastric cancer.

    PubMed

    Lin, Rongbo; Fan, Nanfeng; Wu, Guangfeng; Chen, Ying; Guo, Zengqing; Wang, Xiaojie; Jin, Feng; Chen, Ling; Liu, Jie

    2015-02-01

    The aim of this study was to evaluate the efficacy and safety of paclitaxel plus oxaliplatin plus fluorouracil/leucovorin (POF) as salvage chemotherapy in pretreated advanced gastric cancer. Fifty-two pretreated patients with the advanced gastric cancer were eligible for this study. The POF regimen consisted of a 3-hour infusion of paclitaxel (135 mg/m(2)) followed by oxaliplatin (85 mg/m(2)) and leucovorin (400 mg/m(2)), administered simultaneously over a 2-hour infusion period, followed by an infusion of fluorouracil (2400 mg/m(2)) over a 46-hour period, every 14 days. From an intention-to-treat analysis, overall response rate and stable disease rate were 28.8 and 38.5%, respectively. The median time to progression and overall survival were 4.1 and 7.9 months, respectively. Grade 3 or 4 neutropaenia, thrombocytopaenia, fatigue, and neuropathy were 38.5, 15.4, 17.3, and 15.4%, respectively. The POF regimen is active in pretreated advanced gastric cancer as salvage chemotherapy, with a favourable toxicity profile.

  3. Clinical impact and cost-effectiveness of antiretroviral therapy in India: starting criteria and second-line therapy

    PubMed Central

    Freedberg, Kenneth A.; Kumarasamy, Nagalingeswaran; Losina, Elena; Cecelia, Anitha J.; Scott, Callie A.; Divi, Nomita; Flanigan, Timothy P.; Lu, Zhigang; Weinstein, Milton C.; Wang, Bingxia; Ganesh, Aylur K.; Bender, Melissa A.; Mayer, Kenneth H.; Walensky, Rochelle P.

    2008-01-01

    Background India has more than 5.7 million people infected with human immunodeficiency virus (HIV). In 2004, the Indian government began providing antiretroviral therapy (ART), and there are now an estimated 56 500 people receiving ART. Objective To project the life expectancy, cost, and cost-effectiveness associated with different strategies for using ART in India, to inform treatment programs. Methods We utilized an HIV disease simulation model, incorporating data on natural history, treatment efficacy, and costs of care from India. Input parameters for the simulated cohort included mean age 32.6 years and mean CD4 count 318 cells/μl (SD 291 cells/μl). We examined different criteria for starting and stopping ART with a first-line regimen of stavudine/lamivudine/nevirapine, and the impact of a second-line protease-inhibitor-based regimen. Cost-effectiveness in US dollars per year of life saved (US$/YLS) was compared incrementally among alternative starting, sequencing, and stopping criteria. Results Discounted (undiscounted) mean survival ranged from 34.5 (37.5) months with no ART to 64.7 (73.6) months with one line of therapy initiated at CD4 < 350 cells/μl, to 88.9 (106.5) months with two lines of therapy initiated at CD4 < 350 cells/μl. Lifetime medical costs ranged from US$530 (no ART) to US$5430 (two ART regimens) per person. With one line of therapy, the incremental cost-effectiveness ratios ranged from US$430/YLS to US$550/YLS as the CD4 starting criterion was increased from CD4 < 250 cells/μl to < 350 cells/μl. Use of two lines of therapy had an incremental cost-effectiveness ratio of US$1880/YLS compared with the use of first-line therapy alone. Results were sensitive to the costs of second-line therapy and criteria for stopping therapy. Conclusions In India, antiretroviral therapy will lead to major survival benefits and is cost-effective by World Health Organization criteria. The availability of second-line regimens will further increase survival

  4. Forest structure following tornado damage and salvage logging in northern Maine, USA

    Treesearch

    Shawn Fraver; Kevin J. Dodds; Laura S. Kenefic; Rick Morrill; Robert S. Seymour; Eben Sypitkowski

    2017-01-01

    Understanding forest structural changes resulting from postdisturbance management practices such as salvage logging is critical for predicting forest recovery and developing appropriate management strategies. In 2013, a tornado and subsequent salvage operations in northern Maine, USA, created three conditions (i.e., treatments) with contrasting forest structure:...

  5. Bypass surgery for lower extremity limb salvage: vein bypass.

    PubMed

    El-Sayed, Hosam F

    2012-01-01

    Bypass surgery for limb salvage in cases of chronic limb ischemia is a well-established treatment modality. Use of an autogenous vein provides the best conduit for infrainguinal arterial bypass procedures, particularly for bypass to the infrapopliteal arteries. In this article, we discuss infrainguinal vein bypass surgery including indications, perioperative care, and long-term follow up. We also discuss the outcomes of the procedure with regard to patient survival and limb salvage. The autogenous vein continues to be the best available conduit with the highest patency rate and the best treatment option. Compared to all other revascularization options for infrainguinal disease, the vein bypass has the best limb salvage and long-term survival in patients appropriately selected for the procedure.

  6. FOLFOX-4 as second-line therapy after failure of gemcitabine and platinum combination in advanced gall bladder cancer patients.

    PubMed

    Dodagoudar, Chandragouda; Doval, Dinesh Chandra; Mahanta, Anupam; Goel, Varun; Upadhyay, Amitabh; Goyal, Pankaj; Talwar, Vineet; Singh, Sajjan; John, Mithun Chacko; Tiwari, Srikant; Patnaik, Nivedita

    2016-01-01

    There is no standard second-line chemotherapy after progression on first-line therapy including gemcitabine and platinum combination in advanced gall bladder cancer patients. So this study was undertaken to assess the efficacy and safety of FOLFOX-4 regimen in this setting. In this observational study, patients with performance status ≤2, who progressed on first-line therapy, were enrolled from May 2010 to June 2014. FOLFOX-4 based treatment was administered until progression, unacceptable toxicity or up to 12 cycles. A total of 66 patients were enrolled in this study. The median age of patients was 52.5 years (32-66 years),of which 24 (36.36%) were males and 42 (63.63%) were females. The median number of cycles could be given were 9.5 (2-12). Only 43.93% patients in this study completed full 12 cycles of chemotherapy. Sixteen patients (24.24%) in this study required the dose reduction at least in one cycle of chemotherapy due to toxicities. Disease control rate was seen in 39 (59.09%) patients, with complete response in none, partial response in 16 (24.24%), stable disease in 23 (34.84%) and progressive disease in 27 (40.90%) patients. The median progression free survival was 3.9 months; median overall survival was 7.6 months. The main Grade 3/4 side effects seen were hematological in 31.81% (n = 21) and gastrointestinal in 25.75% (n = 17) patients. Majority of patients (46%) had Grade 1/2 peripheral neuropathy. FOLFOX-4 is an effective and well-tolerated regimen as a second-line treatment in advanced gall bladder cancer patients. Further studies are required, especially in the Indian subcontinent. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  7. Marine Salvage in the United States

    DTIC Science & Technology

    1982-01-01

    marine pollution , one aftermath of shipping casualties. The middle ground between preventing casualties and cleaning up after them encompasses operations...addressed. The separate objectives of saving lives, salving vessels or cargoes (which is the saving of property), and the mitigation of marine pollution are...86 Liability for the Cost of Salvage and for Marine Pollution 88 Paying for Salvage Services 89 National Cognizance of Salvage Posture 90 Salvage

  8. Increasing the use of second-line therapy is a cost-effective approach to prevent the spread of drug-resistant HIV: a mathematical modelling study.

    PubMed

    Nichols, Brooke E; Sigaloff, Kim C E; Kityo, Cissy; Hamers, Raph L; Baltussen, Rob; Bertagnolio, Silvia; Jordan, Michael R; Hallett, Timothy B; Boucher, Charles A B; de Wit, Tobias F Rinke; van de Vijver, David A M C

    2014-01-01

    Earlier antiretroviral therapy (ART) initiation reduces HIV-1 incidence. This benefit may be offset by increased transmitted drug resistance (TDR), which could limit future HIV treatment options. We analyze the epidemiological impact and cost-effectiveness of strategies to reduce TDR. We develop a deterministic mathematical model representing Kampala, Uganda, to predict the prevalence of TDR over a 10-year period. We then compare the impact on TDR and cost-effectiveness of: (1) introduction of pre-therapy genotyping; (2) doubling use of second-line treatment to 80% (50-90%) of patients with confirmed virological failure on first-line ART; and (3) increasing viral load monitoring from yearly to twice yearly. An intervention can be considered cost-effective if it costs less than three times the gross domestic product per capita per quality adjusted life year (QALY) gained, or less than $3420 in Uganda. The prevalence of TDR is predicted to rise from 6.7% (interquartile range [IQR] 6.2-7.2%) in 2014, to 6.8% (IQR 6.1-7.6%), 10.0% (IQR 8.9-11.5%) and 11.1% (IQR 9.7-13.0%) in 2024 if treatment is initiated at a CD4 <350, <500, or immediately, respectively. The absolute number of TDR cases is predicted to decrease 4.4-8.1% when treating earlier compared to treating at CD4 <350 due to the preventative effects of earlier treatment. Most cases of TDR can be averted by increasing second-line treatment (additional 7.1-10.2% reduction), followed by increased viral load monitoring (<2.7%) and pre-therapy genotyping (<1.0%). Only increasing second-line treatment is cost-effective, ranging from $1612 to $2234 (IQR $450-dominated) per QALY gained. While earlier treatment initiation will result in a predicted increase in the proportion of patients infected with drug-resistant HIV, the absolute numbers of patients infected with drug-resistant HIV is predicted to decrease. Increasing use of second-line treatment to all patients with confirmed failure on first-line therapy is a cost

  9. 32 CFR 752.5 - Salvage.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Salvage. 752.5 Section 752.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY CLAIMS ADMIRALTY CLAIMS § 752.5 Salvage. (a) Scope... the jurisdiction of the Department of the Navy, or for salvage services rendered by the Department of...

  10. 25 CFR 700.99 - Salvage value.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Salvage value. 700.99 Section 700.99 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.99 Salvage value. Salvage value means the probable sale price of an...

  11. Changes in second-line regimen durability and continuity of care in relation to national ART guideline changes in South Africa

    PubMed Central

    Onoya, Dorina; Brennan, Alana T; Berhanu, Rebecca; van der Berg, Liudmyla; Buthelezi, Thulasizwe; Fox, Matthew P

    2016-01-01

    Abstract Introduction: Little is known about the impact of antiretroviral therapy (ART) guideline changes on the durability of second-line ART and continuity of care. This study examines predictors of early drug substitutions and treatment interruptions using a cohort analysis of HIV positive adults switched to second-line ART between January 2004 and September 2013 in Johannesburg, South Africa. Methods: The main outcomes were having a drug substitution or treatment interruption in the first 24 months on second-line ART. Kaplan Meiers analyses and Cox proportional hazards regression were used to identify predictors of drug substitutions and treatment interruptions. Results: Of 3028 patients on second-line ART, 353 (11.7%) had a drug substitution (8.6 per 100PY, 95% CI: 7.8–9.6) and 260 (8.6%) had a treatment interruption (6.3 per 100PY, 95% CI: 5.6–7.1). While treatment interruptions decreased from 32.5 per 100PY for the 2004 cohort to 2.3 per 100PY for the 2013 cohort, the rates of drug substitutions steadily increased, peaking at an incidence of 26.7 per 100PY for the 2009 cohort and then decreased to 4.2 per 100PY in the 2011 cohort. Compared to the 2004 to 2008 cohorts, the hazard of early drug substitutions was highest among patients switched to AZT + ddI + LPVr in 2009 to 2010 (aHR 5.1, 95% CI: 3.4–7.1) but remained low over time among patients switched to TDF + 3TC/FTC + LPVr or AZT/ABC + 3TC + LPVr. The main common predictor of both treatment interruption and drug substitution was drug toxicity. Conclusions: Our results show a rapid transition between 2004 and 2010 ART guidelines and concurrent improvements in continuity of care among second-line ART patients. Drug toxicity reporting and monitoring systems need improvements to inform timely regimen changes and ensure that patients remain in care. However, reasons for drug substitutions should be closely monitored to ensure that patients do not run out of treatment options in the future

  12. Clinical outcomes following salvage Gamma Knife radiosurgery for recurrent glioblastoma

    PubMed Central

    Larson, Erik W; Peterson, Halloran E; Lamoreaux, Wayne T; MacKay, Alexander R; Fairbanks, Robert K; Call, Jason A; Carlson, Jonathan D; Ling, Benjamin C; Demakas, John J; Cooke, Barton S; Lee, Christopher M

    2014-01-01

    Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with a survival prognosis of 14-16 mo for the highest functioning patients. Despite aggressive, multimodal upfront therapies, the majority of GBMs will recur in approximately six months. Salvage therapy options for recurrent GBM (rGBM) are an area of intense research. This study compares recent survival and quality of life outcomes following Gamma Knife radiosurgery (GKRS) salvage therapy. Following a PubMed search for studies using GKRS as salvage therapy for malignant gliomas, nine articles from 2005 to July 2013 were identified which evaluated rGBM treatment. In this review, we compare Overall survival following diagnosis, Overall survival following salvage treatment, Progression-free survival, Time to recurrence, Local tumor control, and adverse radiation effects. This report discusses results for rGBM patient populations alone, not for mixed populations with other tumor histology grades. All nine studies reported median overall survival rates (from diagnosis, range: 16.7-33.2 mo; from salvage, range: 9-17.9 mo). Three studies identified median progression-free survival (range: 4.6-14.9 mo). Two showed median time to recurrence of GBM. Two discussed local tumor control. Six studies reported adverse radiation effects (range: 0%-46% of patients). The greatest survival advantages were seen in patients who received GKRS salvage along with other treatments, like resection or bevacizumab, suggesting that appropriately tailored multimodal therapy should be considered with each rGBM patient. However, there needs to be a randomized clinical trial to test GKRS for rGBM before the possibility of selection bias can be dismissed. PMID:24829861

  13. Early Hypofractionated Salvage Radiotherapy for Post-Prostatectomy Biochemical Recurrence

    PubMed Central

    Kruser, Tim J.; Jarrard, David F.; Graf, Andrew K.; Hedican, Sean P.; Paolone, David R.; Wegenke, John D.; Liu, Glenn; Geye, Heather M.; Ritter, Mark A.

    2010-01-01

    Background Post-prostatectomy adjuvant or salvage radiotherapy, when using standard fractionation, requires 6.5–8 weeks of treatment. We report on the safety and efficacy of an expedited radiotherapy course for salvage prostate radiotherapy. Methods A total of 108 consecutive patients were treated with salvage radiation therapy to 65 Gy in 26 fractions of 2.5 Gy. Median follow-up was 32.4 months. Median pre-salvage PSA was 0.44 (0.05–9.50). Eighteen patients (17%) received androgen deprivation following surgery or concurrently with radiation. Results The actuarial freedom from biochemical failure for the entire group at 4 years was 67% +/− 5.3%. An identical 67% control rate was seen at 5 years for the first 50 enrolled patients whose median followup was longer at 43 months. One acute grade 3 GU toxicity occurred, with no acute grade 3 GI and no late grade 3 toxicities observed. On univariate analysis, higher Gleason score (p=0.006), PSA doubling time ≤ 12 months (p=0.03), perineural invasion (p=0.06), and negative margins (p=0.06) showed association with unsuccessful salvage. On multivariate analysis, higher Gleason score (p=0.057) and negative margins (p=0.088) retained an association with biochemical failure. Conclusions Hypofractionated radiotherapy (65 Gy in 2.5 Gy fractions in about 5 weeks) reduces the length of treatment by from 1–1/2 to 3 weeks relative to other treatment schedules commonly employed, produces low rates of loxicity, and demonstrates encouraging efficacy at 4 – 5 years. Hypofractionation may provide a convenient, resource efficient and well-tolerated salvage approach for the estimated 20–35,000 US men per year experiencing biochemical recurrence after prostatectomy. PMID:21656740

  14. A Bayesian network meta-analysis on second-line systemic therapy in advanced gastric cancer.

    PubMed

    Zhu, Xiaofu; Ko, Yoo-Joung; Berry, Scott; Shah, Keya; Lee, Esther; Chan, Kelvin

    2017-07-01

    It is unclear which regimen is the most efficacious among the available therapies for advanced gastric cancer in the second-line setting. We performed a network meta-analysis to determine their relative benefits. We conducted a systematic review of randomized controlled trials (RCTs) through the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases and American Society of Clinical Oncology abstracts up to June 2014 to identify phase III RCTs on advanced gastric cancer in the second-line setting. Overall survival (OS) data were the primary outcome of interest. Hazard ratios (HRs) were extracted from the publications on the basis of reported values or were extracted from survival curves by established methods. A Bayesian network meta-analysis was performed with WinBUGS to compare all regimens simultaneously. Eight RCTs (2439 patients) were identified and contained extractable data for quantitative analysis. Network meta-analysis showed that paclitaxel plus ramucirumab was superior to single-agent ramucirumab [OS HR 0.51, 95 % credible region (CR) 0.30-0.86], paclitaxel (OS HR 0.81, 95 % CR 0.68-0.96), docetaxel (OS HR 0.56, 95 % CR 0.33-0.94), and irinotecan (OS HR 0.71, 95 % CR 0.52-0.99). Paclitaxel plus ramucirumab also had an 89 % probability of being the best regimen among all these regimens. Single-agent ramucirumab, paclitaxel, docetaxel, and irinotecan were comparable to each other with respect to OS and were superior to best supportive care. This is the first network meta-analysis to compare all second-line regimens reported in phase III gastric cancer trials. The results suggest the paclitaxel plus ramucirumab combination is the most effective therapy and should be the reference regimen for future comparative trials.

  15. Second-line chemotherapy in advanced biliary cancer: a systematic review.

    PubMed

    Lamarca, A; Hubner, R A; David Ryder, W; Valle, J W

    2014-12-01

    The randomized NCRN phase III ABC-02 trial provided level-A evidence for first-line chemotherapy with cisplatin and gemcitabine combination in advanced biliary cancer (ABC). This systematic literature review aims to evaluate the level of evidence for the use of second-line chemotherapy for patients with ABC in terms of overall survival (OS), response, toxicity and quality of life. Eligible studies were identified using Medline, ASCO, ESMO and the World Gastrointestinal Congress databases. Searches were last updated on 15 December 2013. Eligible studies reported survival and/or response data for patients with ABC receiving second-line systemic chemotherapy. This systematic review was registered in the PROSPERO database (No. CRD42013004205). Five hundred and fifty-eight studies were identified from the searches in Medline (n = 342), ASCO (n = 160), ESMO (n = 27) and World Gastrointestinal Congress (n = 29). Twenty-five studies were eligible: 14 phase II clinical trials, 9 retrospective analyses and 2 case reports. In total, data from 761 patients were reported with median number of patients included in each study of 22 (range 9-96). The mean OS was 7.2 months [95% confidence interval (CI) 6.2-8.2] [phase II: 6.6 (95% CI 5.1-8.1); retrospective analysis: 7.7 (95% CI 6.5-8.9)]. The mean progression-free survival (PFS), response rate (RR) and disease control rate were 3.2 months (95% CI 2.7-3.7), 7.7% (95% CI 4.6-10.9) and 49.5% (95% CI 41.4-57.7), respectively. The best correlations were between OS and PFS for all studies (r = 0.54; P = 0.01) and between OS and PFS (r = 0.61; P = 0.04) and OS and RR (r = 0.62; P = 0.03) for phase II studies, respectively. Biliary tract cancer is known to be a chemo-responsive disease. There is insufficient evidence (level C) to recommend a second-line chemotherapy schedule in ABC, although the available data suggest that a cohort of patients may benefit. Further prospective and randomized studies are needed to clarify the relative

  16. Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second-Line Therapies

    PubMed Central

    Okimoto, Kenichiro; Arai, Makoto; Saito, Keiko; Minemura, Shoko; Maruoka, Daisuke; Matsumura, Tomoaki; Nakagawa, Tomoo; Katsuno, Tatsuro; Ishii, Chisato; Murata, Shota; Watanabe, Masaharu; Nomura, Fumio; Yokosuka, Osamu

    2014-01-01

    Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third-line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC. PMID:27379339

  17. Hybrid haemodialysis vascular access salvage.

    PubMed

    Potisek, Maja; Ključevšek, Tomaž; Leskovar, Boštjan

    2017-03-01

    A well-functioning vascular access is essential for successful haemodialysis in patients with end-stage kidney failure. Sometimes, when we have exploited all conventional ways of vascular access salvage, we have to find a unique solution to preserve it.

  18. SPS salvage and disposal alternatives

    NASA Technical Reports Server (NTRS)

    1980-01-01

    A wide range of salvage options exist for the satellite power system (SPS) satellite, ranging from use in and beyond geosynchronous orbit to use in low Earth orbit to return and use on Earth. The satellite might be used intact to provide for various purposes, it might be cannibalized, or it might be melted down to supply materials for space- or ground-based products. The use of SPS beyond its nominal lifetime provides value that can be deducted from the SPS capital investment cost. It is shown that the present value of the salvage value of the SPS satellites, referenced to the system initial operation data, is likely to be on the order of five to ten percent of its on-orbit capital cost. (Given a 30 year satellite lifetime and a four percent discount rate, the theoretical maximum salvage value is 30.8 percent of the initial capital cost). The SPS demonstration satellite is available some 30 years earlier than the first full-scale SPS satellite and has a likely salvage value on the order of 80 percent of its on site capital cost. In the event that it becomes desirable to dispose of either the demonstration or full-scale SPS satellite, a number of disposal options appear to exist for which intact disposal costs are less than one percent of capital costs.

  19. Muscle Flaps and Their Role in Limb Salvage

    PubMed Central

    Klebuc, Michael; Menn, Zachary

    2013-01-01

    Muscle flaps have proved to be a valuable and versatile tool in the surgical treatment of the severely compromised lower extremity. Utilized as both local pedicle flaps and free tissue transfers, muscles have been successfully employed to cover complex wounds, manage osteomyelitis, salvage infected vascular grafts, treat recalcitrant venous stasis ulcers, preserve amputation levels, and restore motion following compartment syndrome. Free flap pedicles have also been used in a flow-through fashion to create a distal arterial bypass. This article explores the multipurpose role of muscle flaps in limb salvage surgery and their beneficial physiologic characteristics in hostile wound environments. PMID:23805342

  20. Fourteen- vs seven-day bismuth-based quadruple therapy for second-line Helicobacter pylori eradication

    PubMed Central

    Hwang, Jae Jin; Lee, Dong Ho; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2015-01-01

    AIM: To compare the efficacy of 14- and 7-d bismuth-based quadruple therapies as second-line eradication treatment for Helicobacter pylori (H. pylori) infection. METHODS: Between 2004 and 2014, the medical records of 790 patients who had experienced failure of first-line proton pump inhibitor (PPI)-based eradication therapy and were then treated with bismuth-based quadruple therapy were retrospectively reviewed. Those who received bismuth-based quadruple therapy [PPI, bismuth, metronidazole, and tetracycline (PBMT)] for either 7 d or 14 d were assigned to a PBMT-7 group (n = 543) or a PBMT-14 group (n = 247), respectively. The eradication rates for both groups were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of eradication treatment. RESULTS: The overall ITT eradication rate was 69.1% (546/790). Final ITT eradication rates were 67.4% (366/543; 95%CI: 63.1%-71.7%) in the PBMT-7 group and 72.8% (180/247; 95%CI: 67.4%-78.2%) in the PBMT-14 group (P = 0.028). The overall PP eradication rate was 80.0% (546/682), and the final PP eradication rates were 78.2% (366/468; 95%CI: 72.1%-84.0%) in the PBMT-7 group and 84.1% (180/214; 95%CI: 76.8%-90.8%) in the PBMT-14 group (P = 0.009). The H. pylori eradication rates in the PBMT-14 group were significantly higher than in the PBMT-7 group according to both ITT (P = 0.028) and PP analysis (P = 0.009). Compliance was similar in both groups (PBMT-7 group: 97.9%; PBMT-14 group: 96.4%). Adverse event rates were 10.7% (51/478) and 17.1% (38/222) in the PBMT-7 and PBMT-14 groups, respectively (P = 0.487). CONCLUSION: The 14-d bismuth-based quadruple therapy is a significantly more effective second-line eradication

  1. Efficacy of 14-d vs 7-d moxifloxacin-based triple regimens for second-line Helicobacter pylori eradication.

    PubMed

    Hwang, Jae Jin; Lee, Dong Ho; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2015-05-14

    To evaluate the efficacy of the 14-d moxifloxacin-based triple therapy for the second-line eradication of Helicobacter pylori (H. pylori) infection. Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacin-based triple therapy (oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group (n = 79) while those who took them for 14 days were assigned to RAM-14 group (n = 81). The eradication rates for both groups were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative (13)C-urea breath test 4 wk after the end of the eradication treatment. The overall ITT eradication rate was 76.2% (122/160). The final ITT eradication rates were 70.8% (56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4% (66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group (P = 0.034). The overall PP eradication rate was 84.1% (122/145), and the final PP eradication rates were 77.7% (56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4% (66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group (P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT (P = 0.034) and the PP analyses (P = 0.017). Both groups exhibited good treatment compliance (RAM-7/RAM-14 group: 100%/100%). The adverse event rates were 19.4% (14/72) and 20.5% (15/73) in the RAM-7 and RAM-14

  2. Efficacy of 14-d vs 7-d moxifloxacin-based triple regimens for second-line Helicobacter pylori eradication

    PubMed Central

    Hwang, Jae Jin; Lee, Dong Ho; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

    2015-01-01

    AIM: To evaluate the efficacy of the 14-d moxifloxacin-based triple therapy for the second-line eradication of Helicobacter pylori (H. pylori) infection. METHODS: Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacin-based triple therapy (oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group (n = 79) while those who took them for 14 days were assigned to RAM-14 group (n = 81). The eradication rates for both groups were determined by intention-to-treat (ITT) and per-protocol (PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative 13C-urea breath test 4 wk after the end of the eradication treatment. RESULTS: The overall ITT eradication rate was 76.2% (122/160). The final ITT eradication rates were 70.8% (56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4% (66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group (P = 0.034). The overall PP eradication rate was 84.1% (122/145), and the final PP eradication rates were 77.7% (56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4% (66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group (P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT (P = 0.034) and the PP analyses (P = 0.017). Both groups exhibited good treatment compliance (RAM-7/RAM-14 group: 100%/100%). The adverse event rates were 19.4% (14/72) and 20.5% (15/73) in the

  3. Trends of second-line eradication therapy for Helicobacter pylori in Japan: a multicenter study in the Tokyo metropolitan area.

    PubMed

    Asaoka, Daisuke; Nagahara, Akihito; Matsuhisa, Takeshi; Takahashi, Shin-Ichi; Tokunaga, Kengo; Kawai, Takashi; Kawakami, Kohei; Suzuki, Hidekazu; Suzuki, Masayuki; Nishizawa, Toshihiro; Kurihara, Naoto; Ito, Masayoshi; Sasaki, Hitoshi; Omata, Fumio; Mizuno, Shigeaki; Torii, Akira; Ohkusa, Toshifumi; Mine, Tetsuya; Sakaki, Nobuhiro

    2013-12-01

    In Japan, the eradication rate of first-line therapy for Helicobacter pylori (H. pylori) with a proton pump inhibitor (PPI), amoxicillin (AMPC) and clarithromycin (CAM) has been decreasing because of a high prevalence of CAM resistance. A possible decrease of the eradication rate for second-line therapy with a PPI, AMPC and metronidazole (MNZ) is of concern. The aim of this study is to assess the trends in second-line eradication therapy for H. pylori in Japan. We accumulated data retrospectively on patients administered second-line eradication therapy for Helicobacter pylori with a PPI, AMPC, and MNZ for 1 week after failure of first-line eradication therapy with a PPI, AMPC and CAM at 15 facilities in the Tokyo metropolitan area in Japan from 2007 to 2011. Trends for second-line eradication rates in modified intention-to-treat (ITT) analyses were investigated. Second-line eradication rates were categorized by three PPIs (rabeprazole (RPZ), lansoprazole (LPZ) or omeprazole (OMZ)) and evaluated. We accumulated data on 1373 patients. The overall second-line eradication rate was 92.4%. Second-line eradication rates in 2007, 2008, 2009, 2010 and 2011 were 97.7, 90.6, 94.5, 91.8 and 91.8%, respectively, with no significant trends revealed. Second-line eradication rates categorized by three PPIs for the entire 5-year period were 91.6, 93.4 and 92.4% (RPZ, LPZ and OPZ, respectively) with no significant differences among the three PPIs. From 2007 to 2011, there were no significant trends in the second-line eradication rates and the rates remained consistently high. From the viewpoint of high prevalence of CAM resistance in Japan, triple therapy with PPI, AMPC and MNZ may be a better strategy for first-line therapy compared to triple therapy with PPI, AMPC and CAM. © 2013 John Wiley & Sons Ltd.

  4. Prostate Cancer–Specific Survival Following Salvage Radiotherapy vs Observation in Men With Biochemical Recurrence After Radical Prostatectomy

    PubMed Central

    Trock, Bruce J.; Han, Misop; Freedland, Stephen J.; Humphreys, Elizabeth B.; DeWeese, Theodore L.; Partin, Alan W.; Walsh, Patrick C.

    2011-01-01

    Context Biochemical disease recurrence after radical prostatectomy often prompts salvage radiotherapy, but no studies to date have had sufficient numbers of patients or follow-up to determine whether radiotherapy improves survival, and if so, the subgroup of men most likely to benefit. Objectives To quantify the relative improvement in prostate cancer–specific survival of salvage radiotherapy vs no therapy after biochemical recurrence following prostatectomy, and to identify subgroups for whom salvage treatment is most beneficial. Design, Setting, and Patients Retrospective analysis of a cohort of 635 US men undergoing prostatectomy from 1982–2004, followed up through December 28, 2007, who experienced biochemical and/or local recurrence and received no salvage treatment (n=397), salvage radiotherapy alone (n=160), or salvage radiotherapy combined with hormonal therapy (n=78). Main Outcome Measure Prostate cancer–specific survival defined from time of recurrence until death from disease. Results With a median follow-up of 6 years after recurrence and 9 years after prostatectomy, 116 men (18%) died from prostate cancer, including 89 (22%) who received no salvage treatment, 18 (11%) who received salvage radiotherapy alone, and 9 (12%) who received salvage radiotherapy and hormonal therapy. Salvage radiotherapy alone was associated with a significant 3-fold increase in prostate cancer–specific survival relative to those who received no salvage treatment (hazard ratio [HR], 0.32 [95% confidence interval {CI}, 0.19–0.54]; P<.001). Addition of hormonal therapy to salvage radiotherapy was not associated with any additional increase in prostate cancer–specific survival (HR, 0.34 [95% CI, 0.17–0.69]; P=.003). The increase in prostate cancer–specific survival associated with salvage radiotherapy was limited to men with a prostate-specific antigen doubling time of less than 6 months and remained after adjustment for pathological stage and other established

  5. Cell salvage for minimising perioperative allogeneic blood transfusion

    PubMed Central

    Carless, Paul A; Henry, David A; Moxey, Annette J; O’Connell, Dianne; Brown, Tamara; Fergusson, Dean A

    2014-01-01

    The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective cardiac and orthopaedic surgery. The use of cell salvage did not appear to impact adversely on clinical outcomes. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patients’ treatment status potentially biasing the results in favour of cell salvage. PMID:20393932

  6. Drug Resistance Patterns of Multidrug- and Extensively Drug-Resistant Tuberculosis in Korea: Amplification of Resistance to Oral Second-line Drugs.

    PubMed

    Kim, Chang Ki; Shin, So Youn; Kim, Hee Jin; Lee, Kyungwon

    2017-07-01

    We aimed to analyze the drug resistance patterns of multidrug-resistant and extensively drug-resistant tuberculosis (TB) and the difference of drug resistance among various settings for health care in Korea. The data of drug susceptibility testing in 2009 was analyzed in order to secure sufficient number of patients from various settings in Korea. Patients were categorized by types of institutions into four groups, which comprised new and previously treated patients from public health care centers (PHC), the private sector, and Double-barred Cross clinics (DBC). The resistance rates to first-line drugs were uniformly high in every group. While the resistance rates to second-line drugs were not as high as first-line drugs, there was a pattern that drug resistance rates were lowest for PHC and highest for DBC. The differences of the resistance rates were more prominent for oral second-line drugs. Our findings implied that drug resistance to oral second-line drugs was significantly amplified during multidrug-resistant-TB treatment in Korea. Therefore, an individualized approach is recommended for treating drug-resistant-TB based on susceptibility testing results to prevent acquisition or amplification of drug resistance. © The Korean Society for Laboratory Medicine.

  7. Viral Suppression Following Switch to Second-line Antiretroviral Therapy: Associations With Nucleoside Reverse Transcriptase Inhibitor Resistance and Subtherapeutic Drug Concentrations Prior to Switch

    PubMed Central

    Johnston, Victoria; Cohen, Karen; Wiesner, Lubbe; Morris, Lynn; Ledwaba, Johanna; Fielding, Katherine L.; Charalambous, Salome; Churchyard, Gavin; Phillips, Andrew; Grant, Alison D.

    2014-01-01

    Background. High rates of second-line antiretroviral treatment (ART) failure are reported. The association with resistance and nonadherence on switching to second-line ART requires clarification. Methods. Using prospectively collected data from patients in South Africa, we constructed a cohort of patients switched to second-line ART (1 January 2003 through 31 December 2008). Genotyping and drug concentrations (lamivudine, nevirapine, and efavirenz) were measured on stored samples preswitch. Their association with viral load (VL) <400 copies/mL by 15 months was assessed using modified Poisson regression. Results. One hundred twenty-two of 417 patients (49% male; median age, 36 years) had genotyping (n = 115) and/or drug concentrations (n = 80) measured. Median CD4 count and VL at switch were 177 cells/µL (interquartile range [IQR], 77–263) and 4.3 log10 copies/mL (IQR, 3.8–4.7), respectively. Fifty-five percent (n = 44/80) had subtherapeutic drug concentrations preswitch. More patients with therapeutic vs subtherapeutic ART had resistance (n = 73): no major mutations (3% vs 51%), nonnucleoside reverse transcriptase inhibitor (94% vs 44%), M184V/I (94% vs 26%), and ≥1 thymidine analogue mutations (47% vs 18%), all P = .01; and nucleoside reverse transcriptase inhibitor (NRTI) cross-resistance mutations (26% vs 13%, P = .23). Following switch, 68% (n = 83/122) achieved VL <400 copies/mL. Absence of NRTI mutations and subtherapeutic ART preswitch were associated with failure to achieve VL <400 copies/mL. Conclusions. Nonadherence, suggested by subtherapeutic ART with/without major resistance mutations, significantly contributed to failure when switching regimen. Unresolved nonadherence, not NRTI resistance, drives early second-line failure. PMID:23943851

  8. No Salvage Using High-Dose Chemotherapy Plus/Minus Reirradiation for Relapsing Previously Irradiated Medulloblastoma

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Spreafico, Filippo; Biassoni, Veronica; Luksch, Roberto; Collini, Paola; Solero, Carlo N.; Simonetti, Fabio; Pignoli, Emanuele; Cefalo, Graziella; Poggi, Geraldina; Modena, Piergiorgio Ph.D.; Mariani, Luigi; Potepan, Paolo; Podda, Marta; Casanova, Michela; Pecori, Emilia; Acerno, Stefania; Ferrari, Andrea; Terenziani, Monica

    2009-04-01

    Purpose: Myeloablative regimens were frequently used for medulloblastoma relapsing after craniospinal irradiation (CSI): in 1997-2002, we used repeated surgery, standard-dose and myeloablative chemotherapy, and reirradiation. Methods and Materials: In 10 patients, reinduction included sequential high-dose etoposide, high-dose cyclophosphamide/vincristine, and high-dose carboplatin/vincristine, then two myeloablative courses with high-dose thiotepa ({+-} carboplatin); 6 other patients received two of four courses of cisplatin/etoposide. Hematopoietic precursor mobilization followed high-dose etoposide or high-dose cyclophosphamide or cisplatin/etoposide therapy. After the overall chemotherapy program, reirradiation was prescribed when possible. Results: Seventeen patients were treated: previous treatment included CSI of 19.5-36 Gy with posterior fossa/tumor boost and chemotherapy in 16 patients. Fifteen patients were in their first and 2 in their second and third relapses, respectively. First progression-free survival had lasted a median of 26 months. Relapse sites included leptomeninges in 9 patients, spine in 4 patients, posterior fossa in 3 patients, and brain in 1 patient. Three patients underwent complete resection of recurrence, and 10 underwent reirradiation. Twelve of 14 patients with assessable tumor had an objective response after reinduction; 2 experienced progression and were not given the myeloablative courses. Remission lasted a median of 16 months. Additional relapses appeared in 13 patients continuing the treatment. Fifteen patients died of progression and 1 died of pneumonia 13 months after relapse. The only survivor at 93 months had a single spinal metastasis that was excised and irradiated. Survival for the series as a whole was 11-93 months, with a median of 41 months. Conclusions: Despite responses being obtained and ample use of surgery and reirradiation, second-line therapy with myeloablative schedules was not curative, barring a few

  9. Limb salvage: When, where, and how?

    PubMed Central

    Puri, Ajay

    2015-01-01

    From an era where amputation was the only option to the current day function preserving resections and complex reconstructions has been a major advance in the treatment of musculoskeletal sarcomas. The objectives of extremity reconstruction after oncologic resection include providing skeletal stability where necessary, adequate wound coverage to allow early subsequent adjuvant therapy, optimising the aesthetic outcome and preservation of functional capability with early return to function. This article highlights the concepts of surgical margins in oncology, discusses the principles governing safe surgical resection in these tumors and summarises the current modalities and recent developments relevant to reconstruction after limb salvage. The rationale of choice of a particular resection modality and the unique challenges of reconstruction in skeletally immature individuals are also discussed. Striking the right balance between adequate resection, while yet retaining or reconstructing tissue for acceptable function and cosmesis is a difficult task. Complications are not uncommon and patients and their families need to be counseled regarding the potential setbacks that may occur in the course of their eventual road to recovery, Limb salvage entails a well orchestrated effort involving various specialties and better outcomes are likely to be achieved with centralization of expertise at regional centers. PMID:25593356

  10. A new thiamin salvage pathway.

    PubMed

    Jenkins, Amy Haas; Schyns, Ghislain; Potot, Sébastien; Sun, Guangxing; Begley, Tadhg P

    2007-08-01

    The physiological function for thiaminase II, a thiamin-degrading enzyme, has eluded investigators for more than 50 years. Here, we demonstrate that this enzyme is involved in the regeneration of the thiamin pyrimidine rather than in thiamin degradation, and we identify a new pathway involved in the salvage of base-degraded forms of thiamin. This pathway is widely distributed among bacteria, archaea and eukaryotes. In this pathway, thiamin hydrolysis products such as N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (formylaminopyrimidine; 15) are transported into the cell using the ThiXYZ transport system, deformylated by the ylmB-encoded amidohydrolase and hydrolyzed to 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP; 6)-an intermediate on the de novo thiamin biosynthetic pathway. To our knowledge this is the first example of a thiamin salvage pathway involving thiamin analogs generated by degradation of one of the heterocyclic rings of the cofactor.

  11. Second Line of Defense Megaports Initiative Operational Testing and Evaluation Plan Colon Container Terminal (CCT) Panama

    SciTech Connect

    Newhouse, Robert N.

    2010-01-01

    Report on the Operational Testing and Evaluation to validate and baseline an operable system that meets the Second Line of Defense (SLD) mission requirements. An SLD system is defined as the detection technology and associated equipment, the system operators from the host country, the standard operating procedures (SOPs), and other elements such as training and maintenance which support long-term system sustainment. To this end, the activities conducted during the OT&E phase must demonstrate that the Megaports System can be operated effectively in real-time by Panama Direccion General de Aduanas (DGA Panama Customs) personnel to the standards of the U.S. Department of Energy/National Nuclear Security Administration (DOE/NNSA).

  12. Diabetes therapy--focus on Asia: second-line therapy debate: insulin/secretagogues.

    PubMed

    Eldor, Roy; Raz, Itamar

    2012-12-01

    The following review is based on the second part of a debate entitled 'Diabetes therapy--focus on Asia: 2nd line therapy: GLP1/DPP4 inhibitors versus Secretagogue/insulin therapy', which was held during the '1st Asia Pacific Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy)', in Shanghai, China, 2011. As such we reviewed only insulin and secretagogue therapy despite the existence of other therapeutic options. The article aims to shed light on the circumstances most adequate for use of these as second-line agents, despite possible drawbacks. It is important to emphasize that regardless of it being a review of published evidence, it primarily represents the professional opinion of the writers.

  13. High prevalence of PI resistance in patients failing second-line ART in Vietnam

    PubMed Central

    Thao, Vu Phuong; Quang, Vo Minh; Day, Jeremy N.; Chinh, Nguyen Tran; Shikuma, Cecilia M.; Farrar, Jeremy; Van Vinh Chau, Nguyen; Thwaites, Guy E.; Dunstan, Sarah J.; Le, Thuy

    2016-01-01

    Background There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART. Methods We performed a cross-sectional virological assessment of adults on second-line ART for ≥6 months between November 2006 and December 2011, followed by a prospective follow-up over 2 years of patients with virological failure (VF) at the Hospital for Tropical Diseases, Vietnam. VF was defined as HIV RNA concentrations ≥1000 copies/mL. Resistance mutations were identified by population sequencing of the pol gene and interpreted using the 2014 IAS-USA mutation list and the Stanford algorithm. Logistic regression modelling was performed to identify predictors of VF. Results Two hundred and thirty-one patients were enrolled in the study. The median age was 32 years; 81.0% were male, 95.7% were on a lopinavir/ritonavir-containing regimen and 22 (9.5%) patients had VF. Of the patients with VF, 14 (64%) carried at least one major protease mutation [median: 2 (IQR: 1–3)]; 13 (59%) had multiple protease mutations conferring intermediate- to high-level resistance to lopinavir/ritonavir. Mutations conferring cross-resistance to etravirine, rilpivirine, tipranavir and darunavir were identified in 55%, 55%, 45% and 27% of patients, respectively. Higher viral load, adherence <95% and previous indinavir use were independent predictors of VF. The 2 year outcomes of the patients maintained on lopinavir/ritonavir included: death, 7 (35%); worsening virological/immunological control, 6 (30%); and virological re-suppression, 5 (25%). Two patients were switched to raltegravir and darunavir/ritonavir with good HIV control. Conclusions High-prevalence PI resistance was associated with previous indinavir exposure. Darunavir plus an integrase inhibitor and lamivudine might be a promising third-line regimen in Vietnam. PMID:26661398

  14. Second-line bismuth-containing quadruple therapy for Helicobacter pylori eradication and impact of diabetes

    PubMed Central

    Kim, Sung Eun; Park, Moo In; Park, Seun Ja; Moon, Won; Kim, Jae Hyun; Jung, Kyoungwon; Kim, Hae Koo; Lee, Young Dal

    2017-01-01

    AIM To investigate Helicobacter pylori (H. pylori) eradication rates using second-line bismuth-containing quadruple therapy and to identify predictors of eradication failure. METHODS This study included 636 patients who failed first-line triple therapy and received 7 d of bismuth-containing quadruple therapy between January 2005 and December 2015. We retrospectively demonstrated H. pylori eradication rates with respect to the year of therapy as well as demographic and clinical factors. H. pylori eradication was confirmed by a 13C-urea breath test or a rapid urease test at least 4 wk after the completion of bismuth-based quadruple therapy: proton pump inhibitor, metronidazole, bismuth, and tetracycline. RESULTS The overall eradication rates by intention-to-treat analysis and per-protocol analysis were 73.9% (95%CI: 70.1%-77.4%) and 94.5% (95%CI: 92.4%-96.5%), respectively. Annual eradication rates from 2005 to 2015 were 100.0%, 92.9%, 100.0%, 100.0%, 100.0%, 97.4%, 100.0%, 93.8%, 84.4%, 98.9%, and 92.5%, respectively, by per-protocol analysis. A multivariate analysis showed that diabetes mellitus (OR = 3.99, 95%CI: 1.56-10.20, P = 0.004) was associated with H. pylori eradication therapy failure. CONCLUSION The second-line bismuth-containing quadruple therapy for H. pylori infection is still effective in Korea, and diabetes mellitus is suggested to be a risk factor for eradication failure. PMID:28246480

  15. Second Line Uterotonics and The Risk of Hemorrhage-Related Morbidity

    PubMed Central

    Butwick, Alexander J.; Carvalho, Brendan; Blumenfeld, Yair J; El-Sayed, Yasser Y.; Nelson, Lorene M; Bateman, Brian T.

    2015-01-01

    Objective Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD). Study Design We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders. Results The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 – 2.6). Conclusion In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic. PMID:25582104

  16. Strategy for salvage pedicle screw placement: A technical note.

    PubMed

    Fujibayashi, Shunsuke; Takemoto, Mitsuru; Neo, Masashi; Matsuda, Shuichi

    2013-01-01

    Salvage surgery for failed lumbar spine fusion with a loosened pedicle screw is challenging. In general, the strategy includes replacement with larger and longer pedicle screws, augmentation with polymethylmethacrylate cement or hydroxyapatite granules, and extension of fused segments. The purpose of this study is to introduce a new technique for pedicle screw replacement after failed lumbar spine fusion. Five salvage operations were performed using a different trajectory (DT) pedicle screw replacement technique based on 3-dimensional radiological information. Position of the alternative pedicle screws was planned carefully on the computer screen of a computed tomography-based navigation system before the operation. To obtain sufficient initial stability, 1 of 2 techniques was chosen, depending on the patient. One technique created a completely new route, which did not interfere with the existing screw hole, and the other involved penetration of the existing screw hole. DT pedicle screws were replaced successfully according to the preoperative plan. In all patients, bony union were achieved at the final follow-up period without any instrument failure. Extension of the fused segments could be avoided by using the DT pedicle screw replacement technique combined with transforaminal lumbar interbody fusion. The DT pedicle screw replacement technique is a treatment option for salvage lumbar spine surgery. The current technique is a treatment option for salvage operations that can both avoid extension of a fused segment and achieve successful bony union.

  17. Second-line single-agent chemotherapy in human epidermal growth factor receptor 2-negative metastatic breast cancer: A systematic review.

    PubMed

    Puglisi, Fabio; Rea, Daniel; Kroes, Michel A; Pronzato, Paolo

    2016-02-01

    No 'gold standard' exists for single-agent chemotherapy of human epidermal growth factor receptor 2-negative (HER2-negative) metastatic breast cancer (MBC) in the second-line. The objective of this systematic review is to identify and appraise overall survival (OS), progression-free survival (PFS), time to progression (TTP) and Grade ≥3 adverse event evidence for single-agent chemotherapy in this setting. MEDLINE, Embase and the Cochrane Library were searched to October 2013, and PubMed October 2013 to November 2014. Electronic database searches were supplemented with hand searching of reference lists and conferences. Eligible randomised controlled trials (RCTs) employed at least one single-agent chemotherapy treatment, enrolled HER2-negative or unselected MBC patients who had progressed following first-line chemotherapy within the metastatic setting, and reported outcomes of interest for the second-line setting. Fifty-three RCTs were included in total, with most containing mixed populations by HER2 status and treatment line. Fourteen studies reported data specifically for second- and later-line treatment within the metastatic setting. Median overall survival (OS) in most trials was 8-13 months. Only one trial reported a significant difference between studied interventions in the second-line metastatic setting: nab-paclitaxel (n=131) conferred a statistically significant OS advantage vs. three-weekly paclitaxel (n=136) (median OS 13.0 vs. 10.7 months, respectively; hazard ratio 0.73, p=0.024) and improved overall safety. One RCT demonstrated significant benefit in this setting in confirmed HER2-negative MBC alongside favourable safety. Treatment line terminology was imprecise. To reliably inform patient treatment decisions, quality-of-life data are needed and precise OS estimation according to underlying patient characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Influence of (11)C-choline PET/CT on the treatment planning for salvage radiation therapy in patients with biochemical recurrence of prostate cancer.

    PubMed

    Souvatzoglou, Michael; Krause, Bernd J; Pürschel, Anja; Thamm, Reinhard; Schuster, Tibor; Buck, Andreas K; Zimmermann, Frank; Molls, Michael; Schwaiger, Markus; Geinitz, Hans

    2011-05-01

    The present study evaluates the incidence of (11)C-choline PET/CT positive findings in patients with recurrent prostate cancer referred for salvage radiotherapy (SRT) and the influence on the definition of the planning target volume (PTV). Thirty-seven patients treated with radical prostatectomy and referred to SRT to the prostatic fossa because of biochemical relapse, were analysed retrospectively. All patients underwent (11)C-choline PET/CT before radiotherapy. The influence of PET/CT on the extent of the PTV was analysed. The median total follow up after SRT was 51.2 months. 11/37 (30%) patients had a positive finding in the (11)C-choline PET/CT, 5 (13%) outside of the prostatic fossa (iliac lymph nodes), implicating an extension of the PTV. Patients with positive (11)C-choline PET/CT had a significant higher PSA value than patients with no pathologic uptake (p=0.03). Overall, at the end of follow up 56% of the patients had a PSA ≤ 0.2ng/ml and 44% had a biochemical relapse of prostate cancer. (11)C-choline PET/CT detects abnormalities outside of the prostatic fossa in 13% of patients referred for SRT because of biochemical relapse after radical prostatectomy, affecting the extent of the PTV. Prospective studies need to be implemented to evaluate the benefit of SRT with a PTV based on (11)C-choline PET/CT. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. A prognostic model for survival after salvage treatment with FLAG-Ida +/- gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia.

    PubMed

    Bergua, Juan M; Montesinos, Pau; Martinez-Cuadrón, David; Fernández-Abellán, Pascual; Serrano, Josefina; Sayas, María J; Prieto-Fernandez, Julio; García, Raimundo; García-Huerta, Ana J; Barrios, Manuel; Benavente, Celina; Pérez-Encinas, Manuel; Simiele, Adriana; Rodríguez-Macias, Gabriela; Herrera-Puente, Pilar; Rodríguez-Veiga, Rebeca; Martínez-Sánchez, María P; Amador-Barciela, María L; Riaza-Grau, Rosalía; Sanz, Miguel A

    2016-09-01

    The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG-Ida or FLAG-Ida plus Gentuzumab-Ozogamicin (FLAGO-Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG-Ida and 38 FLAGO-Ida; 92 were older than 60 years. The complete remission (CR)/CR with incomplete blood count recovery (CRi) rate was 51%, with 9% of induction deaths. Three covariates were associated with lower CR/CRi: high-risk cytogenetics and t(8;21) at diagnosis, no previous allogeneic stem cell transplantation (allo-SCT) and relapse-free interval <1 year. Allo-SCT was performed in second CR in 60 patients (23%). The median overall survival (OS) of the entire cohort was 0·7 years, with 22% OS at 5-years. Four independent variables were used to construct the score: cytogenetics, FLT3-internal tandem duplication, length of relapse-free interval and previous allo-SCT. Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor-risk (45%), with an expected 5-year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long-term outcome using FLAG-Ida/FLAGO-Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.

  20. Salvage surgery in patients with recurrent or residual squamous cell carcinoma of the anus.

    PubMed

    Alamri, Y; Buchwald, P; Dixon, L; Dobbs, B; Eglinton, T; McCormick, J; Wakeman, C; Frizelle, F A

    2016-11-01

    Anal squamous cell cancers are uncommon, and primary treatment is radical chemoradiotherapy. The role of radical surgery is in salvage of patients with residual and recurrent disease. The primary aim of the study is to determine how often such salvage surgery is required, while the secondary aim is to determine which features indicate salvage surgery may be required and to determine the outcome of salvage surgery. A prospective database was analysed of all patients with anal cancer over an 18 year period (Dec 1996-Jan 2015). The records of patients requiring salvage surgery were reviewed. 203 Patients were identified with anal cancers, of which 180 had squamous cell anal carcinoma. 112 Female (median age 59.4, range 33-92) 68 male (median age 63.8 range 36-87). Of these 27 patients (15%) required salvage surgery. 23 Patients had a R0 resection. 18 Patients had an extended resection (16 R0) while 9 had a routine APR (7 R0). The 30-day post-operative mortality rate was 0%. The overall 5 year survival was 78%, not significantly different from those not requiring salvage surgery (p = 0.23). Age, gender, AJCC stage, T stage, radiation therapy alone, were not predicators of the need for salvage surgery. Salvage surgery is uncommonly required. Extended surgery beyond routine APR is often required to obtain an R0 resection. Excellent patient survival can be achieved in highly selected cases. There were no identifiable clinical predictors of those needing salvage surgery, and consideration should be given to explore molecular and genetic factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Similar survival but better function for patients after limb salvage versus amputation for distal tibia osteosarcoma.

    PubMed

    Mavrogenis, Andreas F; Abati, Caterina Novella; Romagnoli, Carlo; Ruggieri, Pietro

    2012-06-01

    Amputation has been the standard surgical treatment for distal tibia osteosarcoma. Advances in surgery and chemotherapy have made limb salvage possible. However, it is unclear whether limb salvage offers any improvement in function without compromising survival. We therefore compared the survival, local recurrence, function, and complications of patients with distal tibia osteosarcoma treated with limb salvage or amputation. We retrospectively reviewed 42 patients with distal tibia osteosarcoma treated from 1985 to 2010. Nineteen patients had amputations and 23 had limb salvage and allograft reconstructions. We graded the histology using Broders classification, and staged patients using the Musculoskeletal Tumor Society (MSTS) and American Joint Committee on Cancer (AJCC) systems. The tumor grades tended to be higher in the group of patients who had amputations. We determined survival, local recurrence, MSTS function, and complications. The minimum followup was 8 months (median, 60 months; range, 8-288 months). The survival of patients who had limb salvage was similar to that of patients who had amputations: 84% at 120 and 240 months versus 74%, respectively. The incidence of local recurrence was similar: three of 23 patients who had limb salvage versus no patients who had amputations. The mean MSTS functional score tended to be higher in patients who had limb salvage compared with those who had amputations: 76% (range, 30%-93%) versus 71% (range, 50%-87%), respectively. The incidence of complications was similar. Patients treated with either limb salvage or amputation experience similar survival, local recurrence, and complications, but better function is achievable for patients treated with limb salvage versus amputation. Local recurrence and complications are more common in patients with limb salvage. Level III, retrospective comparative study. See the Guidelines for Authors for a complete description of levels of evidence.

  2. Autologous stem cell transplantation: an effective salvage therapy in multiple myeloma.

    PubMed

    Lemieux, Emilie; Hulin, Cyrille; Caillot, Denis; Tardy, Stéphanie; Dorvaux, Véronique; Michel, Jessica; Gastinne, Thomas; Rossi, Cédric; Legouge, Caroline; Touzeau, Cyrille; Planche, Lucie; Loirat, Marion; Lafon, Ingrid; Moreau, Philippe

    2013-03-01

    Eighty-one patients treated with high-dose therapy and autologous stem cell transplantation (ASCT) as part of salvage therapy after a frontline ASCT were included in a retrospective analysis. The median time between the first and the salvage ASCT was 47 months. After salvage ASCT, 75 patients (93%) achieved at least a partial response, including 67% very good partial responses, and no toxic death was reported. Sixteen patients (20%) underwent consolidation therapy, whereas 30 patients (37%) underwent some form of maintenance therapy after salvage ASCT. For all patients, the median overall survival (OS) was 10 years from diagnosis and 4 years from salvage ASCT. The median progression-free survival (PFS) from the date of the first ASCT to the date of the first relapse was 40 months, and the median PFS from the date of salvage ASCT to the date of subsequent progression was 18 months. In the multivariate analysis of prognostic factors, three independent factors unfavorably affected PFS: a short duration of response to the first ASCT (cut-off value of 24 months), a response less than a very good partial response after salvage therapy, and no maintenance treatment after salvage ASCT. Age over 60 years and a short duration of response after the first ASCT were the two factors adversely affecting OS from the time of diagnosis and OS from the time of salvage ASCT. Our data show that salvage ASCT is a feasible option that should be routinely considered at the time of relapse for patients with a response duration of more than 2 years to frontline high-dose therapy.

  3. GenoType® Mtbdrsl assay for resistance to second-line anti-tuberculosis drugs

    PubMed Central

    Theron, Grant; Peter, Jonny; Richardson, Marty; Warren, Rob; Dheda, Keertan; Steingart, Karen R

    2016-01-01

    Background Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. Objectives To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. Search methods We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. Selection criteria We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Data collection and analysis Two review authors independently extracted data and assessed

  4. [What is the objective of second-line chemotherapy after failure of first-line chemotherapy in hormone-resistant metastatic prostate?].

    PubMed

    El Demery, Mounira; Pouessel, Damien; Avancès, Christophe; Iborra, François; Rebillard, Xavier; Faix, Antoine; Ségui, Bruno; Delbos, Olivier; Ayuso, Didier; Culine, Stéphane

    2006-06-01

    Chemotherapy occupies an increasingly important place in the management of hormone-resistant metastatic prostate cancer. For the first time in this disease, docetaxel increases the survival of patients, with a modest, but definite median gain of about 2 months. In everyday practice, the indication for second-line chemotherapy after immediate or delayed failure of first-line chemotherapy is sometimes considered, although objective data concerning its efficacy are limited. The objective of the present study was to retrospectively evaluate the results obtained with second-line chemotherapy in a patient cohort managed at the Montpellier Regional Cancer Centre. Clinical characteristics, treatments delivered and outcome of 43 patients who received two successive lines of chemotherapy were retrospectively collected by means of a standardized questionnaire. Three groups of patients were defined as a function of the chemotherapy protocols delivered: docetaxel alone or in combination, mitoxantrone and other protocols not comprising either docetaxel or mitoxantrone. Responses to chemotherapy were analysed according to three criteria: objective responses, laboratory responses and palliative responses. At the time of second-line chemotherapy, the median age of the patients was 69 years (range: 46 to 83). The median interval between the end of first-line chemotherapy and the start of second-line chemotherapy was 3 months (range: 1 to 15). The protocols administered comprised docetaxel alone (12 patients) or in combination with cisplatin (4 patients), mitoxantrone in 13 patients, or other cytotoxic molecules such as vinblastine, doxorubicin or etoposide in combination with a platinum salt (14 patients). The median number of cycles delivered was 4 (range: 1 to 10). No objective response was observed. Six (14%) patients obtained a laboratory response. A palliative response was observed in 16 (37%) patients, 7 of whom were treated with a docetaxel-based protocol, 6 were treated with

  5. The EGFR tyrosine kinase inhibitors as second-line therapy for EGFR wild-type non-small-cell lung cancer: a real-world study in People’s Republic of China

    PubMed Central

    Xu, Jianlin; Ding, Guozheng; Zhang, Xueyan; Jin, Bo; Lou, Yuqing; Zhang, Yanwei; Wang, Huiming; Wu, Dan; Han, Baohui

    2016-01-01

    Introduction Clinical evidence comparing chemotherapy and tyrosine kinase inhibitors (TKIs) as second-line therapy for epidermal growth factor receptor (EGFR) wild-type non-small-cell lung cancer (NSCLC) are conflicting. Methods We retrospectively reviewed stage IV EGFR wild-type NSCLC patients who relapsed on first-line chemotherapy at the Shanghai Chest Hospital to compare the efficacy of TKIs and chemotherapy as second-line therapy among different clinical subgroups. Results The progression-free survival (PFS) and overall survival for patients receiving chemotherapy as second-line therapy for NSCLC were longer than patients who received TKIs. The hazard ratios (HRs) were 0.40 (P<0.001) and 0.50 (P<0.001), respectively. Subgroup analyses showed that second-line TKI therapy resulted in inferior PFS among smokers (HR =0.24, P<0.001), males (HR =0.33, P<0.001), females (HR =0.54, P=0.004), and patients with adenocarcinoma (HR =0.48, P<0.001) and nonadenocarcinoma histology (HR =0.20, P<0.001). Among never-smokers, the PFS in cohorts receiving second-line chemotherapy or TKIs was not significantly different (HR =0.70, P=0.08). Conclusion These results suggest that EGFR TKI therapy was inferior compared to chemotherapy in EGFR wild-type NSCLC patients who relapsed from first-line chemotherapy; however, among never-smokers, these two treatment strategies were comparable. PMID:27799795

  6. Rill Erosion in Post Wildfire Forests after Salvage Logging

    NASA Astrophysics Data System (ADS)

    Robichaud, Peter; Wagenbrenner, Joseph; Brown, Robert

    2016-04-01

    Despite the dominance of concentrated flow or rill erosion in the erosion processes especially in steep forest environments that have been affected by wildfire or management activities few studies have quantified these effects on rill erosion. This study quantified the effects of wildfire and post-fire timber salvage operations on rill runoff quantity, runoff velocity, and rill erosion. Simulated rill experiments were conducted at various sites in the Western US after wildfire and timber salvage operations. The onsite conditions consists of burned only, salvage logged, skid or snig trail, or skid trails with extra logging debris added. For each rill experiment, concentrated flow was applied at the top of the plot through an energy dissipater at five inflow rates for 12 min each. Runoff was sampled every 2 min and runoff volume and sediment concentration were determined for each sample. The runoff velocity was measured using a dyed calcium chloride solution and two conductivity probes placed a known distance apart. Runoff volume, runoff velocities, and sediment concentrations increased with increasing levels of disturbance. The burned only plots had lower runoff rates and sediment concentrations than any of the other disturbances. The salvage logged plots had greater responses than the burn only plots and the mitigation treatment had a marginal effect on runoff ratios, runoff velocities and sediment concentrations. These results suggest that additional disturbance after a wildfire can increase the erosional response and that proper erosion control mitigation may be an important consideration for post fire management to reduce onsite erosion.

  7. Limb salvage in musculoskeletal oncology: Recent advances

    PubMed Central

    Puri, Ajay

    2014-01-01

    The treatment of musculoskeletal sarcomas has made vast strides in the last few decades. From an era where amputation was the only option to the current day function preserving resections and complex reconstructions has been a major advance. The objectives of extremity reconstruction after oncologic resection include providing skeletal stability where necessary, adequate wound coverage to allow early subsequent adjuvant therapy, optimising the aesthetic outcome and preservation of functional capability with early return to function. This article highlights the concepts of surgical margins in oncology, discusses the principles governing safe surgical resection in these tumors and summarises the current modalities and recent developments relevant to reconstruction after limb salvage. The rationale of choice of a particular resection modality, the unique challenges of reconstruction in skeletally immature individuals and the impact of adjuvant modalities like chemotherapy and radiotherapy on surgical outcomes are also discussed. PMID:25190911

  8. Bypass surgery in limb salvage: inflow procedures.

    PubMed

    Bismuth, Jean; Duran, Cassidy

    2013-04-01

    Proper management of lower-extremity inflow vessel disease is critical to the success of distal interventions. Aortobifemoral bypass is the most effective means of treating aortoiliac disease, but this invasive procedure is not always ideal for a patient population that often has diffuse vascular disease and multiple comorbidities. Technologic advances and increasing experience have fundamentally altered the management algorithm for lower-extremity vascular lesions, and endovascular options have become the first-line therapy for Trans-Atlantic Inter-Society Guidelines (TASC) class A and B lesions. In fact, an endovascular first approach is being endorsed even for highly complex TASC C and even TASC D lesions. Other alternatives include minimally invasive (laparoscopic or robotic) options or extra-anatomic bypass procedures. Inadequate outflow can compromise any inflow procedure, but inflow treatment failures are the crux of all limb salvage in patients with lower-extremity vascular disease.

  9. Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type 2 Diabetes in China

    PubMed Central

    Gu, Shuyan; Zeng, Yuhang; Yu, Demin; Hu, Xiaoqian; Dong, Hengjin

    2016-01-01

    Objective This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone. Methods Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer’s perspective and estimated over a patient’s lifetime. Results SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses. Conclusion SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment. PMID:27875596

  10. Cost-Effectiveness of Saxagliptin versus Acarbose as Second-Line Therapy in Type 2 Diabetes in China.

    PubMed

    Gu, Shuyan; Zeng, Yuhang; Yu, Demin; Hu, Xiaoqian; Dong, Hengjin

    2016-01-01

    This study assessed the long-term cost-effectiveness of saxagliptin+metformin (SAXA+MET) versus acarbose+metformin (ACAR+MET) in Chinese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on MET alone. Systematic literature reviews were performed to identify studies directly comparing SAXA+MET versus ACAR+MET, and to obtain diabetes-related events costs which were modified by hospital surveys. A Cardiff Diabetes Model was used to estimate the long-term economic and health treatment consequences in patients with T2DM. Costs (2014 Chinese yuan) were calculated from the payer's perspective and estimated over a patient's lifetime. SAXA+MET predicted lower incidences of most cardiovascular events, hypoglycemia events and fatal events, and decreased total costs compared with ACAR+MET. For an individual patient, the quality-adjusted life-years (QALYs) gained with SAXA+MET was 0.48 more than ACAR+MET at a cost saving of ¥18,736, which resulted in a cost saving of ¥38,640 per QALY gained for SAXA+MET versus ACAR+MET. Results were robust across various univariate and probabilistic sensitivity analyses. SAXA+MET is a cost-effective treatment alternative compared with ACAR+MET for patients with T2DM in China, with a little QALYs gain and lower costs. SAXA is an effective, well-tolerated drug with a low incidence of adverse events and ease of administration; it is anticipated to be an effective second-line therapy for T2DM treatment.

  11. A comparison of bird communities in burned and salvage-logged, clearcut, and forested Florida Sand Pine scrub.

    Treesearch

    Cathryn H. Greenberg; Lawrence D. Harris; Daniel G Neary

    1995-01-01

    We hypothesized that similar bird assemblages will occur in like-structured habitat that results from both clearcutting and high-intensity wildfire followed by salvage logging. To test this, we compared bird communities of sand pine scrub in mature forest and three disturbance treatments (1) high-intensity wildfire, salvage logged, and naturally regenerated, (2)...

  12. Pyrosequencing for rapid detection of Mycobacterium tuberculosis second-line drugs and ethambutol resistance.

    PubMed

    Lacoma, Alicia; Molina-Moya, Barbara; Prat, Cristina; Pimkina, Edita; Diaz, Jessica; Dudnyk, Andriy; García-Sierra, Nerea; Haba, Lucía; Maldonado, Jose; Samper, Sofia; Ruiz-Manzano, Juan; Ausina, Vicente; Dominguez, Jose

    2015-11-01

    The aim of this work was to study the diagnostic accuracy of pyrosequencing to detect resistance to fluoroquinolones, kanamycin, amikacin, capreomycin, and ethambutol (EMB) in Mycobacterium tuberculosis clinical strains. One hundred four clinical isolates previously characterized by BACTEC 460TB/MGIT 960 were included. Specific mutations were targeted in gyrA, rrs, eis promoter, and embB. When there was a discordant result between BACTEC and pyrosequencing, Genotype MTBDRsl (Hain Lifescience, Nehren, Germany) was performed. Sensitivity and specificity of pyrosequencing were 70.6% and 100%, respectively, for fluoroquinolones; 93.3% and 81.7%, respectively, for kanamycin; 94.1% and 95.9%, respectively, for amikacin; 90.0% and 100%, respectively, for capreomycin; and 64.8% and 87.8%, respectively, for EMB. This study shows that pyrosequencing may be a useful tool for making early decisions regarding second-line drugs and EMB resistance. However, for a correct management of patients with suspected extensively drug-resistant tuberculosis, susceptibility results obtained by molecular methods should be confirmed by a phenotypic method. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Study, Feasibility of Undersea Salvage Simulation.

    ERIC Educational Resources Information Center

    Bowen, H. M.; Hale, Allen

    The training requirements associated with equipment and systems utilized in underwater salvage operations and with the diving activities which are a part of underwater salvage operations are examined. The major emphasis of the study was on the training conditions suitable for the diver. It was found that divers are best trained in a tank or in…

  14. High efficacy of gemifloxacin-containing therapy in Helicobacter Pylori eradication: A pilot empirical second-line rescue therapy.

    PubMed

    Mahmoudi, Laleh; Farshad, Shohreh; Seddigh, Mehrdad; Mahmoudi, Paria; Ejtehadi, Fardad; Niknam, Ramin

    2016-10-01

    Helicobacter pylori (H pylori) is a common gastric pathogen which is associated with chronic gastritis, peptic ulcer, and gastric cancer. It has worldwide distribution with higher incidence in developing countries. Gemifloxacin is a fluoroquinolone antibiotic with documented in vitro activity against H pylori. Considering that there is no clinical data to verify gemifloxacin efficacy in H pylori eradication, this pilot clinical trial was designed. This prospective pilot study was performed during February 2014 to February 2015. A regimen of gemifloxacin (320 mg single dose) plus twice daily doses of amoxicillin1g, bismuth 240 mg, and omeprazole 20 mg for 14 days were prescribed for H pylori infected patients in whom a first-line standard quadruple therapy (clarithromycin-amoxicillin-bismuth-omeprazole) had failed. To confirm H pylori eradication a 13C-urea breath test was performed 4 weeks after treatment.Compliance and incidence of adverse effects were evaluated by questionnaires. A total of 120 patients were enrolled consecutively; out of which 106 patients achieved H pylori eradication; per-protocol and intention-to-treat eradication rates were 91.4% (95% CI: 85.5-97.6) and 88.3% (95% CI: 75.4-92.4) respectively. Three patients (2.5%) failed to take at least 80% of the drugs and excluded from the final analysis. Adverse effects were reported in 42% of patients, most commonly including nausea (15%) and diarrhea (13.3%), which was intense in 1 patient and led to the discontinuation of treatment. In total, 96.7% (116/120) of the patients took the medications correctly. This study revealed that gemifloxacin-containing quadruple therapy provides high H pylori eradication rate (≥90% PP cure rate), and this agent can be included in the list of second-line H pylori therapeutic regimens.

  15. Postoperative Prostate-Specific Antigen Velocity Independently Predicts for Failure of Salvage Radiotherapy After Prostatectomy

    SciTech Connect

    King, Christopher R. Presti, Joseph C.; Brooks, James D.; Gill, Harcharan; Spiotto, Michael T.

    2008-04-01

    Purpose: Identification of patients most likely to benefit from salvage radiotherapy (RT) using postoperative (postop) prostate-specific antigen (PSA) kinetics. Methods and Materials: From 1984 to 2004, 81 patients who fit the following criteria formed the study population: undetectable PSA after radical prostatectomy (RP); pathologically negative nodes; biochemical relapse defined as a persistently detectable PSA; salvage RT; and two or more postop PSAs available before salvage RT. Salvage RT included the whole pelvic nodes in 55 patients and 4 months of total androgen suppression in 56 patients. The median follow-up was >5 years. All relapses were defined as a persistently detectable PSA. Kaplan-Meier and Cox proportional hazards multivariable analysis were performed for all clinical, pathological, and treatment factors predicting for biochemical relapse-free survival (bRFS). Results: There were 37 biochemical relapses observed after salvage RT. The 5-year bRFS after salvage RT for patients with postop prostate-specific antigen velocity {<=}1 vs. >1 ng/ml/yr was 59% vs. 29%, p = 0.002. In multivariate analysis, only postop PSAV (p = 0.0036), pre-RT PSA level {<=}1 (p = 0.037) and interval-to-relapse >10 months (p = 0.012) remained significant, whereas pelvic RT, hormone therapy, and RT dose showed a trend (p = {approx}0.06). PSAV, but not prostate-specific antigen doubling time, predicted successful salvage RT, suggesting an association of zero-order kinetics with locally recurrent disease. Conclusions: Postoperative PSA velocity independently predicts for the failure of salvage RT and can be considered in addition to high-risk features when selecting patients in need of systemic therapy following biochemical failure after RP. For well-selected patients, salvage RT can achieve high cure rates.

  16. Diabetic limb salvage procedure with bone allograft and free flap transfer: a case report

    PubMed Central

    Godoy-Santos, Alexandre L.; Amodio, Daniel T.; Pires, André; Lima, Ana L. M.; Wei, Teng H.; de Cesar-Netto, Cesar; Armstrong, David G.

    2017-01-01

    ABSTRACT The aim of this case report was to describe a successful diabetic limb salvage procedure in the treatment of an infected diabetic foot ulcer through a multidisciplinary team approach and complex surgical reconstruction involving a femoral head bone allograft and musculocutaneous latissimus dorsi free flap. The decision to proceed with aggressive staged efforts at diabetic limb salvage should be made only after careful consultation with the patient, his or her family, and the rest of the multidisciplinary healthcare team. PMID:28326158

  17. Peripheral neuropathy in HIV patients in sub-Saharan Africa failing first-line therapy and the response to second-line ART in the EARNEST trial.

    PubMed

    Arenas-Pinto, Alejandro; Thompson, Jennifer; Musoro, Godfrey; Musana, Hellen; Lugemwa, Abbas; Kambugu, Andrew; Mweemba, Aggrey; Atwongyeire, Dickens; Thomason, Margaret J; Walker, A Sarah; Paton, Nicholas I

    2016-02-01

    Sensory peripheral neuropathy (PN) remains a common complication in HIV-positive patients despite effective combination anti-retroviral therapy (ART). Data on PN on second-line ART is scarce. We assessed PN using a standard tool in patients failing first-line ART and for 96 weeks following a switch to PI-based second-line ART in a large Randomised Clinical Trial in Sub-Saharan Africa. Factors associated with PN were investigated using logistic regression. Symptomatic PN (SPN) prevalence was 22% at entry (N = 1,251) and was associated (p < 0.05) with older age (OR = 1.04 per year), female gender (OR = 1.64), Tuberculosis (TB; OR = 1.86), smoking (OR = 1.60), higher plasma creatinine (OR = 1.09 per 0.1 mg/dl increase), CD4 count (OR = 0.83 per doubling) and not consuming alcohol (OR = 0.55). SPN prevalence decreased to 17% by week 96 (p = 0.0002) following similar trends in all study groups (p = 0.30). Asymptomatic PN (APN) increased over the same period from 21 to 29% (p = 0.0002). Signs suggestive of PN (regardless of symptoms) returned to baseline levels by week 96. At weeks 48 and 96, after adjusting for time-updated associations above and baseline CD4 count and viral load, SPN was strongly associated with TB (p < 0.0001). In summary, SPN prevalence was significantly reduced with PI-based second-line therapy across all treatment groups, but we did not find any advantage to the NRTI-free regimens. The increase of APN and stability of PN-signs regardless of symptoms suggest an underlying trend of neuropathy progression that may be masked by reduction of symptoms accompanying general health improvement induced by second-line ART. SPN was strongly associated with isoniazid given for TB treatment.

  18. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study

    PubMed Central

    Murakami, Kazunari; Sakurai, Yuuichi; Shiino, Madoka; Funao, Nobuo; Nishimura, Akira; Asaka, Masahiro

    2016-01-01

    Objective The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy. Design A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment. Results Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated. Conclusion Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer. Trial registration number NCT01505127. PMID:26935876

  19. GenoType(®) MTBDRsl assay for resistance to second-line anti-tuberculosis drugs.

    PubMed

    Theron, Grant; Peter, Jonny; Richardson, Marty; Warren, Rob; Dheda, Keertan; Steingart, Karen R

    2016-09-08

    Genotype® MTBDRsl (MTBDRsl) is a rapid DNA-based test for detecting specific mutations associated with resistance to fluoroquinolones and second-line injectable drugs (SLIDs) in Mycobacterium tuberculosis complex. MTBDRsl version 2.0 (released in 2015) identifies the mutations detected by version 1.0, as well as additional mutations. The test may be performed on a culture isolate or a patient specimen, which eliminates delays associated with culture. Version 1.0 requires a smear-positive specimen, while version 2.0 may use a smear-positive or -negative specimen. We performed this updated review as part of a World Health Organization process to develop updated guidelines for using MTBDRsl. To assess and compare the diagnostic accuracy of MTBDRsl for: 1. fluoroquinolone resistance, 2. SLID resistance, and 3. extensively drug-resistant tuberculosis, indirectly on a M. tuberculosis isolate grown from culture or directly on a patient specimen. Participants were people with rifampicin-resistant or multidrug-resistant tuberculosis. The role of MTBDRsl would be as the initial test, replacing culture-based drug susceptibility testing (DST), for detecting second-line drug resistance. We searched the following databases without language restrictions up to 21 September 2015: the Cochrane Infectious Diseases Group Specialized Register; MEDLINE; Embase OVID; Science Citation Index Expanded, Conference Proceedings Citation Index-Science, and BIOSIS Previews (all three from Web of Science); LILACS; and SCOPUS; registers for ongoing trials; and ProQuest Dissertations & Theses A&I. We reviewed references from included studies and contacted specialists in the field. We included cross-sectional and case-control studies that determined MTBDRsl accuracy against a defined reference standard (culture-based DST, genetic sequencing, or both). Two review authors independently extracted data and assessed quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We

  20. [Resistance to second-line anti-tuberculosis drugs among peruvian multidrug resistant Mycobacterium tuberculosis strains].

    PubMed

    Barletta, Francesca; Zamudio, Carlos; Rigouts, Leen; Seas, Carlos

    2014-01-01

    To determine the drug resistance profiles for quinolones: ciprofloxacin (CFX), ofloxacin (OFX), moxifloxacin (MFX), and gatifloxacin (GFX); and for injectables: kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) in multidrug resistant (MDR) strains. We also investigated the correlation between mutations in rrs, tlyA and gyrA/B genes, and the in vitro resistance to the second-line anti-tuberculosis drugs. In this pilot study we selected MDR clinical isolates collected from June-December 2004 in the Tropical Medicine Institute "Alexander von Humboldt" (Lima, Perú). The Minimum Inhibitory Concentration (MIC) of CFX, OFX, MFX, GFX, KAN, AMK and CAP for 14 clinical isolates were determined and the sequences of rrs, tlyA and gyrA/B genes were analyzed by conventional PCR followed by sequencing. We obtained valid results for 11 samples. Four isolates were resistant to injectable drugs, and in all the cases the MICs were; >120 µg/mL for KAN and >160 µg/mL for AMK and CAP. Only 2 isolates were resistant to OFX with MIC = 4 µg/mL. Sequencing results suggested that the mutation A1401T in rrs gene could be the molecular cause of the resistance to injectable drugs. In this study we did not find any mutation in tlyA and gyrA/B associated to resistance. Our study suggests a possible association between the mutation A1401T in rrs and resistance to injectable drugs. However further studies should be done to confirm this hypothesis in Perú.

  1. Response to second-line erlotinib in an EGFR mutation-negative patient with non-small-cell lung cancer: make no assumptions

    PubMed Central

    Karam, I.; Melosky, B.

    2012-01-01

    Erlotinib—an oral tyrosine kinase inhibitor (tki) of the epidermal growth factor receptor (egfr)—has commonly been used as a therapeutic option in metastatic non-small-cell lung cancer (nsclc) patients in the second- or third-line treatment setting. A mutation in the EGFR gene (EGFR M+) confers an increased response to this class of drugs. In the first-line setting, use of tkis is restricted to patients having a mutation. The importance of this biomarker has been questioned in subsequent treatment lines. Here, we report a case showing a positive response to erlotinib treatment in the second-line setting. The patient, an elderly male smoker with stage iv nsclc, had a tumour that was EGFR mutation-negative (wild-type EGFR). Based on this clinical case, we discuss the controversy concerning the need for, and impact of, testing for EGFR mutation after first-line treatment. PMID:22328842

  2. Salvage surgery for locoregional recurrences of advanced pharyngolaryngeal squamous cell carcinoma after organ preservation failure.

    PubMed

    López Delgado, I; Riestra Ayora, J; Arenas Brítez, O; García López, I; Martínez Guirado, T; Scola Yurrita, B

    2014-12-01

    Organ preservation treatment for advanced head and neck squamous cell carcinoma is associated with poor outcomes due to locoregional recurrences. Salvage surgery is the main therapeutic option for some of these patients. The aim of this study was to analyse the results of salvage surgery for advanced pharyngolaryngeal squamous cell carcinoma previously treated with radiochemotherapy. We performed a retrospective study on 38 patients (36 men, 2 women). The median age at diagnosis was 60 years with a mean follow-up period of 49.8 months. Recurrences were diagnosed at a mean of 395 days after finalising organ preservation treatment. Patients went under different salvage surgeries, including 22 total laryngectomies, 6 partial laryngectomies (3 transoral laser surgeries and 3 opened surgeries), 8 functional neck dissections and 2 tongue base surgeries. Nineteen patients had no postoperative complications after a mean hospital stay of 2 weeks. However, 5 patients died of significant recurrent bleedings. There were 4 salivary fistulas that responded to conservative management, while 7 patients had important pharyngostomas that required reconstruction with either regional or free flaps. The mean hospital stay was of 61.60 days for all patients. Five-year overall survival from diagnosis, overall survival after salvage surgery and survival after salvage surgery were 44.20, 37.90 and 45.70%, respectively. In summary, we conclude that salvage surgery is an optimal treatment for pharyngolaryngeal and regional recurrences and provides improvement in locoregional control and survival, despite the severe complications.

  3. Endoscopic submucosal tunnel dissection salvage technique for ulcerative early gastric cancer.

    PubMed

    Choi, Hyuk Soon; Chun, Hoon Jai; Seo, Min Ho; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck; Ryu, Ho Sang

    2014-07-21

    Endoscopic submucosal dissection is an effective treatment modality for early gastric cancer (EGC), though the submucosal fibrosis found in ulcerative EGC is an obstacle for successful treatment. This report presents two cases of ulcerative EGC in two males, 73- and 80-year-old, with severe fibrosis. As endoscopic ultrasonography suggested that the EGCs had invaded the submucosal layer, the endoscopic submucosal tunnel dissection salvage technique was utilized for complete resection of the lesions. Although surgical gastrectomy was originally scheduled, the two patients had severe coronary heart disease, and surgeries were refused because of the risks associated with their heart conditions. The endoscopic submucosal tunnel dissection salvage technique procedures described in these cases were performed under conscious sedation, and were completed within 30 min. The complete en bloc resection of EGC using endoscopic submucosal tunnel dissection salvage technique was possible with a free resection margin, and no other complications were noted during the procedure. This is the first known report concerning the use of the endoscopic submucosal tunnel dissection salvage technique salvage technique for treatment of ulcerative EGC. We demonstrate that endoscopic submucosal tunnel dissection salvage technique it is a feasible method showing several advantages over endoscopic submucosal dissection for cases of EGC with fibrosis.

  4. A Randomized Control Trial Comparing 2 Levofloxacin-Containing Second-Line Therapies for Helicobacter pylori Eradication.

    PubMed

    Chuah, Seng-Kee; Liang, Chih-Ming; Lee, Chen-Hsiang; Chiou, Shue-Shian; Chiu, Yi-Chun; Hu, Ming-Luen; Wu, Keng-Liang; Lu, Lung-Sheng; Chou, Yeh-Pin; Chang, Kuo-Chin; Kuo, Chung-Huang; Kuo, Chung-Mou; Hu, Tsung-Hui; Tai, Wei-Chen

    2016-05-01

    Summary of Trial Design.Lengthy exposure to quinolone-containing triple therapy in Helicobacter pylori eradication leads to the development of drug resistance. Sequential therapy with a quinolone and metronidazole -containing regimen appears to be an effective treatment option. This randomized controlled trial aimed to compare the efficacy of 5-plus 5 days' levofloxacin and metronidazole-containing sequential therapy (EALM) with that of 10-day levofloxacin-containing triple therapy (EAL) in second-line H pylori eradication treatment.One hundred and sixty-four patients who had failed the H pylori eradication attempts using the standard triple therapy (proton pump inhibitor bid, clarithromycin 500 mg bid, amoxicillin 1 g bid × 7 days) were randomly assigned to either an EALM therapy group (n = 82; esomeprazole 40 mg bid and amoxicillin 1 g bid for 5 days, followed by esomeprazole 40 mg bid, levofloxacin 500 mg qd, and metronidazole 500 mg tid, for 5 days) or a 10-day EAL therapy group (n = 82; levofloxacin 500 mg qd, amoxicillin 1 g bid, and esomeprazole 40 mg bid). One patient was lost to follow-up in each group. Follow-up for H pylori status was performed 4 to 8 weeks later.Eradication rates for the EALM and EAL groups were 90.2% (74/82, 95% confidence interval [CI] = 83.7%-96.8%) and 80.5% (66/82, 95% CI = 71.7%-89.2%, P = 0.077) in the intention-to-treat analysis; and 91.4% (74/81, 95% CI = 85.1%-97.6%) and 81.5% (66/81, 95% CI = 72.8%-90.1%, P = 0.067) in the per-protocol analysis. The adverse events for the EALM and EAL groups were 23.5% versus 11.1%, P = 0.038 but were all very mild and were well tolerated except for 1 patient with poor compliance. The compliances were 98.8% and 100%, respectively, between the 2 groups. An antibiotic resistance to levofloxacin was the clinical factor influencing the efficacy of H. pylori eradication therapy in the EAL group, and dual resistance to levofloxacin and

  5. Second-line ramucirumab therapy for advanced hepatocellular carcinoma (REACH): an East Asian and non-East Asian subgroup analysis

    PubMed Central

    Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Kudo, Masatoshi; Yang, Ling; Abada, Paolo B.; Cheng, Rebecca; Orlando, Mauro; Zhu, Andrew X.; Okusaka, Takuji

    2016-01-01

    Purpose REACH investigated second-line ramucirumab therapy for advanced hepatocellular carcinoma. Results Median overall survival was 8.2 months for ramucirumab and 6.9 months for placebo (HR, 0.835; 95% CI, 0.634–1.100; p = 0.2046) for East Asians, and 10.1 months for ramucirumab and 8.0 months for placebo (HR, 0.895; 95% CI, 0.690–1.161; p = 0.4023) for non-East Asians. Median overall survival in patients with baseline alpha-fetoprotein ≥ 400 ng/mL was 7.8 months for ramucirumab and 4.2 months for placebo (HR, 0.749; 95% CI, 0.519–1.082; p = 0.1213) for East Asians (n = 139), and 8.2 months for ramucirumab and 4.5 months for placebo (HR, 0.579; 95% CI, 0.371–0.904; p = 0.0149) for non-East Asians (n = 111). The most common grade ≥ 3 treatment-emergent adverse events in East Asians and non-East Asians included hypertension and malignant neoplasm progression. Materials and methods A post-hoc analysis of East Asians (N = 252) and non-East Asians (N = 313) in the intent-to-treat population was performed. Conclusions In East Asians and non-East Asians, ramucirumab did not significantly prolong overall survival. In patients with baseline alpha-fetoprotein ≥ 400 ng/mL, a potentially larger survival benefit was observed in both subgroups. Safety for East Asians was similar to non-East Asians. PMID:27776351

  6. Second-line ramucirumab therapy for advanced hepatocellular carcinoma (REACH): an East Asian and non-East Asian subgroup analysis.

    PubMed

    Park, Joon Oh; Ryoo, Baek-Yeol; Yen, Chia-Jui; Kudo, Masatoshi; Yang, Ling; Abada, Paolo B; Cheng, Rebecca; Orlando, Mauro; Zhu, Andrew X; Okusaka, Takuji

    2016-11-15

    REACH investigated second-line ramucirumab therapy for advanced hepatocellular carcinoma. Median overall survival was 8.2 months for ramucirumab and 6.9 months for placebo (HR, 0.835; 95% CI, 0.634-1.100; p = 0.2046) for East Asians, and 10.1 months for ramucirumab and 8.0 months for placebo (HR, 0.895; 95% CI, 0.690-1.161; p = 0.4023) for non-East Asians. Median overall survival in patients with baseline alpha-fetoprotein ≥ 400 ng/mL was 7.8 months for ramucirumab and 4.2 months for placebo (HR, 0.749; 95% CI, 0.519-1.082; p = 0.1213) for East Asians (n = 139), and 8.2 months for ramucirumab and 4.5 months for placebo (HR, 0.579; 95% CI, 0.371-0.904; p = 0.0149) for non-East Asians (n = 111). The most common grade ≥ 3 treatment-emergent adverse events in East Asians and non-East Asians included hypertension and malignant neoplasm progression. A post-hoc analysis of East Asians (N = 252) and non-East Asians (N = 313) in the intent-to-treat population was performed. In East Asians and non-East Asians, ramucirumab did not significantly prolong overall survival. In patients with baseline alpha-fetoprotein ≥ 400 ng/mL, a potentially larger survival benefit was observed in both subgroups. Safety for East Asians was similar to non-East Asians.

  7. The clinical and bacteriological factors for optimal levofloxacin-containing triple therapy in second-line Helicobacter pylori eradication.

    PubMed

    Tai, Wei-Chen; Lee, Chen-Hsiang; Chiou, Shue-Shian; Kuo, Chung-Mou; Kuo, Chung-Huang; Liang, Chih-Ming; Lu, Lung-Sheng; Chiu, Chien-Hua; Wu, Keng-Liang; Chiu, Yi-Chun; Hu, Tsung-Hui; Chuah, Seng-Kee

    2014-01-01

    Quinolone has the disadvantage of easily acquired drug resistance. It is important to prescribe it wisely for a high eradication rate. The current study aimed to determine the clinical and bacteriological factors for optimal levofloxacin-containing triple therapies in second-line H. pylori eradication. We enrolled a total of 158 H. pylori-infected patients who failed H. pylori eradication using the 7-day standard triple therapy (proton-pump inhibitor [PPI] twice daily, 500 mg clarithromycin twice daily, and 1 g amoxicillin twice daily). They were prescribed with either a 10-day (group A) or 14-day (group B) levofloxacin-containing triple therapy group (levofloxacin 500 mg once daily, amoxicillin 1 g twice daily, and esomeprazole 40 mg twice daily for 10 days) by their clinicians. Follow-up studies to assess treatment responses were carried out 8 weeks later. The eradication rates attained by groups A and B were 73.6% (95% confidence interval [CI]  = 63.9-85.3%) and 90.5% (95% CI = 84.5-98.1%), respectively in the per protocol analysis (P = 0.008 in the per protocol analysis) and 67.1% (95% CI = 56.6-78.5%) and 84.8% (95% CI = 76.8-93.4%), respectively, in the intention-to-treat analysis (P = 0.009). The subgroup analysis revealed that H. pylori eradication rates for group A patients with levofloxacin-susceptible strains were 92.9% (13/14) but it dropped to 12.5% (1/8) when levofloxacin-resistant strains existed. H. pylori was eradicated among all the group B patients with levofloxacin-susceptible strains, but only half of patients with levofloxacin-resistant strains were successfully eradicated. In conclusion, this study confirms the effectiveness of 14-day treatment. Importantly, the results imply that 10-day treatment duration should be optimal if a culture can be performed to confirm the existence of susceptible strains. The duration of H. pylori eradication and levofloxacin resistance were the influencing factors for successful treatment. This study suggests

  8. Salvaging the Infected Breast Tissue Expander: A Standardized Multidisciplinary Approach

    PubMed Central

    Selber, Jesse C.; Crosby, Melissa; Raad, Issam I.; Butler, Charles E.; Villa, Mark T.; Kronowitz, Steven J.; Clemens, Mark W.; Garvey, Patrick; Yang, Wei; Baumann, Donald P.

    2016-01-01

    Background: Infections of breast tissue expander (TE) are complex, often requiring TE removal and hospitalization, which can delay further adjuvant therapy and add to the overall costs of breast reconstruction. Therefore, to reduce the rate of TE removal, hospitalization, and costs, we created a standardized same-day multidisciplinary outpatient quality improvement protocol for diagnosing and treating patients with early signs of TE infection. Methods: We prospectively evaluated 26 consecutive patients who developed a surgical site infection between February 2013 and April 2014. On the same day, patients were seen in the Plastic Surgery and Infectious Diseases clinics, underwent breast ultrasonography with or without periprosthetic fluid aspiration, and were prescribed a standardized empiric oral or intravenous antimicrobial regimen active against biofilm-embedded microorganisms. All patients were managed as per our established treatment algorithm and were followed up for a minimum of 1 year. Results: TEs were salvaged in 19 of 26 patients (73%). Compared with TE-salvaged patients, TE-explanted patients had a shorter median time to infection (20 vs 40 days; P = 0.09), a significantly higher median temperature at initial presentation [99.8°F; interquartile range (IQR) = 2.1 vs 98.3°F; IQR = 0.4°F; P = 0.01], and a significantly longer median antimicrobial treatment duration (28 days; IQR = 27 vs 21 days; IQR = 14 days; P = 0.05). The TE salvage rates of patients whose specimen cultures yielded no microbial growth, Staphylococcus species, and Pseudomonas were 92%, 75%, and 0%, respectively. Patients who had developed a deep-seated pocket infection were significantly more likely than those with superficial cellulitis to undergo TE explantation (P = 0.021). Conclusions: Our same-day multidisciplinary diagnostic and treatment algorithm not only yielded a TE salvage rate higher than those previously reported but also decreased the rate of hospitalization, decreased

  9. Excimer laser with adjunctive balloon angioplasty and heparin-coated self-expanding stent grafts for the treatment of femoropopliteal artery in-stent restenosis: twelve-month results from the SALVAGE study.

    PubMed

    Laird, John R; Yeo, Khung Keong; Rocha-Singh, Krishna; Das, Tony; Joye, James; Dippel, Eric; Reddy, Bhagat; Botti, Charles; Jaff, Michael R

    2012-11-01

    The aim of the study is to evaluate the safety and effectiveness of treating femoropopliteal in-stent restenosis (ISR) with debulking with excimer laser followed by implantation of a VIABAHN endoprosthesis. The optimal treatment strategy for femoropopliteal ISR is unclear. The SALVAGE study is a multicenter prospective registry involving nine US centers. Patients with femoropopliteal ISR with moderate to severe intermittent claudication or critical limb ischemia (Rutherford categories 2-5) and an ankle-brachial index (ABI) =0.8 were treated with excimer laser and the VIABAHN endoprosthesis. The primary efficacy endpoint is primary patency at 12 months as measured by duplex ultrasonography. The primary safety endpoint is the major adverse event (MAE) rate at 30 days. Twenty-seven patients were enrolled. The mean lesion length was 20.7 ± 10.3 cm. The majority of lesions were TASC (TASC I) C and D (81.4%). All lesions were pretreated with excimer laser and percutaneous transluminal angioplasty (PTA) prior to VIABAHN implantation. Technical success was achieved in 100% of cases. There were no MAE at 30 days. Primary patency at 12 months was 48%. The ankle brachial index increased from 0.58 ± 0.24 at baseline to 0.90 ± 0.17 at 12 months. There was improvement in all quality-of-life parameters. The 12-month TLR rate was 17.4%. The strategy of excimer laser atherectomy and PTA followed by implantation of a self-expanding stent graft for the treatment of femoropopliteal ISR is safe and associated with high procedural success. Primary patency rate at 12-months was suboptimal; however, the TLR rate was low. Copyright © 2012 Wiley Periodicals, Inc.

  10. U.S. second line of defense: preventing nuclear smuggling across Russia's borders

    SciTech Connect

    Ball, D. Y.

    1998-11-16

    Preventing the theft of weapons-usable highly enriched uranium and plutonium in Russia is one of the central security concerns facing the US today. The dissolution of the highly centralized USSR and the resulting societal crisis has endangered Russia's ability to protect its more than 200 metric tons of plutonium and 1000 tons of highly enriched uranium (roughly 8 kg Pu or 25 kg HEU is sufficient to make a bomb). Producing this fissile material is the most difficult and expensive part of nuclear weapons production and the US must make every effort to ensure that fissile material (and nuclear-related technologies) does not reach the hands of terrorist groups, rogue states or other potential proliferators. In response to this concern, the US has undertaken a number of initiatives in partnership with Russia and other FSU states to prevent the theft of fissile material. The Material Protection, Control and Accounting Program (MPC&A) was begun in 1993 to prevent the theft of nuclear materials from Russian civilian complexes, that is facilities not under control of the Ministry of Defense, which is largely responsible for possession and oversight of nuclear weapons. The MPC&A program is considered the first line of defense against theft of nuclear material because its goal is to prevent theft of material at production and storage facilities. This year the Department of Energy (DOE) initiated a new program called the Second Line of Defense (SLD), the goal of which is to assist Russia in preventing the smuggling of nuclear material and weapons at its borders, either by land, sea or air. The SLD program represents an important phase in the overall effort to ensure the security of nuclear material and weapons in Russia. However, as the US engages Russian customs officials in this important project, Americans should keep in mind that providing equipment--even indigenous equipment--is insufficient by itself; material aid must be accompanied by rigorous inspection and

  11. Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) study.

    PubMed

    Tiosano, L; Segal, O; Mathalone, N; Pollack, A; Ehrlich, R; Klemperer, I; Barak, Y; Moroz, I; Chowers, I; Goldstein, M

    2017-02-17

    PurposeThe purpose of this study is to evaluate an early switch to aflibecept in eyes with neovascular age-related macular degeneration (nvAMD) showing partial or lack of response for initial therapy with bevacizumab.MethodsThe Aflibercept as a Second Line Therapy for Neovascular Age Related Macular Degeneration in Israel (ASLI) was a prospective, multicenter, single-arm clinical trial. Eyes with nvAMD having incomplete response to 3-9 prior bevacizumab injections were recruited. Three monthly intravitreal aflibercept (2 mg) injections were administered, followed by two bi-monthly injections and a final examination at week 28. An optional injection was allowed at week 20.ResultsForty-seven eyes of 46 patients (mean±SD age 76±8 years) were recruited. The mean number of prior bevacizumab injections was 5.5±2.9. The mean visual acuity improved from 60.3±10 ETDRS letters at baseline to 63.1±15 letters at week 28 (P=0.02, paired t-test). The central subfield thickness (CST) reduced from 409±127 micron at baseline to 330±110 microns at week 4 (P=0.0002; paired t-test), and 277±70 microns at week 28 (P=0.00002; paired t-test). Twenty-two eyes had three to five prior bevacizumab injections (mean 5.1±0.7), and 25 eyes had six to nine prior injections (7.32±1.2). Both groups had reduced CST from baseline to week 28 (P=0.0004 and P=0.0007; paired t-test, respectively). Thirty-five (75%) eyes required the optional additional aflibercept injection at week 20.ConclusionsThe ASLI study demonstrated improved BCVA and reduced CST following an early switch to aflibercept therapy in eyes with prior incomplete response to initial therapy with three to nine bevacizumab injections.Eye advance online publication, 17 February 2017; doi:10.1038/eye.2017.7.

  12. Role of free testosterone levels in patients with metastatic castration-resistant prostate cancer receiving second-line therapy

    PubMed Central

    von Klot, Christoph A.; Kuczyk, Markus A.; Boeker, Alena; Reuter, Christoph; Imkamp, Florian; Herrmann, Thomas R.W.; Tezval, Hossein; Kramer, Mario W.; Perner, Sven; Merseburger, Axel S.

    2017-01-01

    the cutoff level (43.6 vs. 17.3 months, respectively, P=0.0063). Upon multivariate Cox regression analysis, the mean FT concentration during treatment remained a significant prognostic factor for CSS (hazard ratio, 1.22; 95% confidence interval, 1.03–1.43; P=0.0182). In conclusion, in patients with mCRPC, the serum FT level is a strong predictor of CSS in patients under therapy with second-line anti-hormonal therapeutic medication and chemotherapy. It may be concluded that FT levels should be included into the routine control of androgen suppression while under treatment with ADT and second-generation hormonal therapy. PMID:28123517

  13. Target hepatic artery regional chemotherapy and bevacizumab perfusion in liver metastatic colorectal cancer after failure of first-line or second-line systemic chemotherapy.

    PubMed

    Chen, Hui; Zhang, Ji; Cao, Guang; Liu, Peng; Xu, Haifeng; Wang, Xiaodong; Zhu, Xu; Gao, Song; Guo, Jianhai; Zhu, Linzhong; Zhang, Pengjun

    2016-02-01

    Colorectal cancer liver metastasis (CRLM) is a refractory disease after failure of first-line or second-line chemotherapy. Bevacizumab is recommended as first-line therapy for advanced colorectal cancer, but is unproven in CRLM through the hepatic artery. We report favorable outcomes with targeted vessel regional chemotherapy (TVRC) for liver metastatic gastric cancer. TVRC with FOLFOX and bevacizumab perfusion through the hepatic artery was attempted for CRLM for efficacy and safety evaluation. In a single-institution retrospective observational study, 246 patients with CRLM after at least first-line or second-line failure of systemic chemotherapy received TVRC with FOLFOX (i.e. oxaliplatin, leucovorin, and 5-fluorouracil). Of 246 patients, 63 were enrolled into two groups: group 1 (n=30) received bevacizumab and TVRC following tumor progression during previous TVRC treatments; group 2 (n=33) received TVRC plus bevacizumab for CRLM on initiating TVRC. There were no significant differences in the median survival time (14.7 vs. 13.2 months, P=0.367), although the median time to progression was significant (3.3 vs. 5.5 months, P=0.026) between groups. No severe adverse events related to TVRC plus bevacizumab perfusion occurred. Target vessel regional chemotherapy with FOLFOX plus bevacizumab perfusion through the hepatic artery was effective and safe in CRLM. The optimal combination of TVRC and bevacizumab needs further confirmation in future phase II-III clinical trials.

  14. Intranuclear protein transduction through a nucleoside salvage pathway.

    PubMed

    Hansen, James E; Tse, Chung-Ming; Chan, Grace; Heinze, Emil R; Nishimura, Robert N; Weisbart, Richard H

    2007-07-20

    Regulation of gene expression by intranuclear transduction of macromolecules such as transcription factors is an alternative to gene therapy for the treatment of numerous diseases. The identification of an effective intranuclear delivery vehicle and pathway for the transport of therapeutic macromolecules across plasma and nuclear membranes, however, has posed a significant challenge. The anti-DNA antibody fragment 3E10 Fv has received attention as a novel molecular delivery vehicle due to its penetration into living cells with specific nuclear localization, absence of toxicity, and successful delivery of therapeutic cargo proteins in vitro and in vivo. Elucidation of the pathway that allows 3E10 Fv to cross cell membranes is critical to the development of new molecular therapies. Here we show that 3E10 Fv penetrates cells through a nucleoside salvage transporter. 3E10 Fv is unable to penetrate into cells deficient in the equilibrative nucleoside transporter ENT2, and reconstitution of ENT2 into ENT2-deficient cells restores 3E10 Fv transport into cell nuclei. Our results represent the first demonstration of protein transport through a nucleoside salvage pathway. We expect that our finding will facilitate a variety of methods of gene regulation in the treatment of human diseases, open up new avenues of research in nucleoside salvage pathways, and enhance our understanding of the pathophysiology of autoimmune diseases.

  15. A Cost-Utility Analysis of Amputation versus Salvage for Gustilo IIIB and IIIC Open Tibial Fractures

    PubMed Central

    Chung, Kevin C.; Saddawi-Konefka, Daniel; Haase, Steven C.; Kaul, Gautam

    2009-01-01

    Background: Lower extremity trauma is common. Despite an abundance of literature on severe injuries that can be treated with salvage or amputation, the appropriate management of these injuries remains uncertain. In this situation, a cost-utility analysis is an important tool in providing evidence-based practice an approach to guide treatment decisions. Methods: Costs following amputation and salvage were derived from data presented in a study that emerged from the Lower Extremity Assessment Project. We extracted relevant data on projected lifetime costs and analyzed them to include discounting and sensitivity analysis for consider patient age. The utilities for the various health states (amputation or salvage, including possible complications) were previously measured using the standard gamble method and a decision tree simulation to determine quality-adjusted life years (QALYs). Results: Amputation is more expensive than salvage independent of varied ongoing prosthesis needs, discount rate, and patient age at presentation. Moreover, amputation yields fewer QALYs than salvage. Salvage is deemed the dominant, cost-saving strategy. Conclusions: Unless the injury is so severe that salvage is not a possibility, based on this economic model, surgeons should consider limb salvage, which will yield lower costs and higher utility when compared to amputation. PMID:19952652

  16. Salvage chemotherapy for gestational trophoblastic neoplasia: Utility or futility?

    PubMed

    Essel, Kathleen G; Bruegl, Amanda; Gershenson, David M; Ramondetta, Lois M; Naumann, R Wendel; Brown, Jubilee

    2017-07-01

    To determine the efficacy of chemotherapy after failed initial treatment in patients with high risk gestational trophoblastic neoplasia (GTN). We performed a retrospective IRB-approved chart review of all patients with GTN seen at a single institution from 1985 to 2015, including all patients who failed initial treatment. We summarized clinical characteristics with descriptive statistics and estimated progression-free survival (PFS) and overall survival (OS) with the Kaplan-Meier method. Of 68 identified patients, 38 required >2 chemotherapy regimens. Patients were treated for GTN (n=53), including choriocarcinoma, persistent GTN, and invasive mole; for placental site trophoblastic tumor (PSTT) (n=5); and for intermediate trophoblastic tumor (ITT) (n=10). Patients with GTN had a median of 2 salvage regimens, median PFS of 4.0months, and median OS was not reached at median follow-up of 71.2months. Active regimens included EMACO, MAC, BEP, platinum- and etoposide-based combination therapies, and ICE; 8 of 53 patients died of disease (DOD). Patients with PSTT had a median of 3 salvage regimens, median PFS of 2.8months, and median OS of 38.8months. Active regimens included ICE and EMA-EP; 4 of 5 patients DOD. Patients with ITT had a median of 3 salvage regimens, median PFS of 4.1months, and median OS of 38.2months. Active regimens included liposomal doxorubicin, platinum-containing regimens, EMA-CO, and EMA-EP; 7 of 10 patients DOD. Several salvage chemotherapy regimens demonstrate activity in high risk GTN. Multiple regimens may be required and cure is not universal. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Robotic Salvage Lymph Node Dissection After Radical Prostatectomy.

    PubMed

    Torricelli, Fabio C M; Cividanes, Arnaldo; Guglielmetti, Giuliano B; Coelho, Rafael F

    2015-01-01

    Radical prostatectomy is a first-line treatment for localized prostate cancer. However, in some cases, biochemical recurrence associated with imaging-detected nodal metastases may happen. Herein, we aim to present the surgical technique for salvage lymph node dissection after radical prostatectomy. A 70 year-old asymptomatic man presented with a prostate-specific antigen (PSA) of 7.45 ng/mL. Digital rectal examination was normal and trans-rectal prostate biopsy revealed a prostate adenocarcinoma Gleason 7 (3+4). Pre-operative computed tomography scan and bone scintigraphy showed no metastatic disease. In other service, the patient underwent a robotic-assisted radical prostatectomy plus obturador lymphadenectomy. Pathologic examination showed a pT3aN0 tumor. After 6 months of follow-up, serum PSA was 1.45 ng/mL. Further investigation with 11C--Choline PET/CT revealed only a 2-cm lymph node close to the left internal iliac artery. The patient was counseled for salvage lymph node dissection. Salvage lymph node dissection was uneventfully performed. Operative time was 1.5 hour, blood loss was minimal, and there were no intra- or postoperative complications. The patient was discharged from hospital in the 1st postoperative day. After 12 months of follow-up, his PSA was undetectable with no other adjuvant therapy. Robotic salvage pelvic lymph node dissection is an effective option for treatment of patients with biochemical recurrence after radical prostatectomy and only pelvic lymph node metastasis detected by C11-Choline PET/CT.

  18. Salvage treatment with lenalidomide and dexamethasone in relapsed/refractory mantle cell lymphoma: clinical results and effects on microenvironment and neo-angiogenic biomarkers

    PubMed Central

    Zaja, Francesco; De Luca, Stefano; Vitolo, Umberto; Orsucci, Lorella; Levis, Alessandro; Salvi, Flavia; Rusconi, Chiara; Ravelli, Erika; Tucci, Alessandra; Bottelli, Chiara; Balzarotti, Monica; Brusamolino, Ercole; Bonfichi, Maurizio; Pileri, Stefano A.; Sabattini, Elena; Volpetti, Stefano; Monagheddu, Chiara; Vacca, Angelo; Ria, Roberto; Fanin, Renato

    2012-01-01

    Background Preclinical studies have highlighted the activity of lenalidomide in mantle cell lymphoma and its anti-proliferative synergy with dexamethasone. Design and Methods In this prospective, multicenter, phase II study, patients with relapsed/refractory mantle cell lymphoma who were not eligible for, or had relapsed after, intensive treatments received lenalidomide 25 mg/day (days 1–21 of each 28-day cycle) and dexamethasone (40 mg/day on days 1, 8, 15, and 22) for up to 12 months. Results The primary end-points, overall and complete response rates, were achieved by 17 of 33 (52%; 95% confidence interval [CI], 35–68%) and 8 of 33 patients (24%; 95% CI, 13–41%), respectively, by the end of treatment. Fifteen patients (45%) discontinued treatment prematurely, 13 due to lack of response. The median progression-free and overall survival were 12 months (95% CI, 5–19 months) and 20 months (95% CI, 12 months to not estimable), respectively. Treatment resulted in a significant increase in microvessel density (P=0.033) and non-significant increases in macrophage and natural killer cell counts, while serum levels of neoangiogenic factors did not change significantly. Grade 3/4 adverse events were neutropenia (53%), leukopenia (25%), thrombocytopenia (22%), infections (12%), and febrile neutropenia (12%). Conclusions These results confirm a favorable safety and activity profile of lenalidomide in relapsed/refractory mantle cell lymphoma. The contribution of dexamethasone in achieving these results is unclear because of its possible detrimental effect on the immune activation generated by lenalidomide and a higher risk of developing infectious complications. (clinicaltrials.gov identifier: NCT00786851). PMID:22058200

  19. Adenine and adenosine salvage in Leishmania donovani.

    PubMed

    Boitz, Jan M; Ullman, Buddy

    2013-08-01

    6-aminopurine metabolism in Leishmania is unique among trypanosomatid pathogens since this genus expresses two distinct routes for adenine salvage: adenine phosphoribosyltransferase (APRT) and adenine deaminase (AAH). To evaluate the relative contributions of APRT and AAH, adenine salvage was evaluated in Δaprt, Δaah, and Δaprt/Δaah null mutants of L. donovani. The data confirm that AAH plays the dominant role in adenine metabolism in L. donovani, although either enzyme alone is sufficient for salvage. Adenosine salvage was also evaluated in a cohort of null mutants. Adenosine is also primarily converted to hypoxanthine, either intracellularly or extracellularly, but can also be phosphorylated to the nucleotide level by adenosine kinase when the predominant pathways are genetically or pharmacologically blocked. These data provide genetic verification for the relative contributions of 6-aminopurine metabolizing pathways in L. donovani and demonstrate that all of the pathways can function under appropriate conditions of genetic or pharmacologic perturbation.

  20. The potential of a multiplex high-throughput molecular assay for early detection of first and second line tuberculosis drug resistance mutations to improve infection control and reduce costs: a decision analytical modeling study.

    PubMed

    Van't Hoog, A H; Bergval, I; Tukvadze, N; Sengstake, S; Aspindzelashvili, R; Anthony, R M; Cobelens, F

    2015-10-26

    Molecular resistance detection (MRD) of resistance to second-line anti-tuberculous drugs provides faster results than phenotypic tests, may shorten treatment and allow earlier separation among patients with and without second-line drug resistance. In a decision-analytical model we simulated a cohort of patients diagnosed with TB in a setting where drug resistant TB is highly prevalent and requires initial hospitalization, to explore the potential benefits of a high-throughput MRD-assay for reducing potential nosocomial transmission of highly resistant strains, and total costs for diagnosis of drug resistance, treatment and hospitalization. In the base case scenario first-line drug resistance was diagnosed with WHO-endorsed molecular tests, and second-line drug resistance with culture and phenotypic methods. Three alternative scenarios were explored, each deploying high-throughput MRD allowing either detection of second-line mutations in cultured isolates, directly on sputum, or MRD with optimized markers. Compared to a base case scenario, deployment of high-throughput MRD reduced total costs by 17-21 %. The period during which nosocomial transmission may take place increased by 15 % compared to the base case if MRD had currently reported suboptimal sensitivity and required cultured isolates; increased by 7 % if direct sputum analysis were possible including in patients with smear-negative TB, and reduced by 24 % if the assay had improved markers, but was still performed on cultured isolates. Improved clinical sensitivity of the assay (additional markers) by more than 35 % would be needed to avoid compromising infection control. Further development of rapid second-line resistance testing should prioritize investment in optimizing markers above investments in a platform for direct analysis of sputum.

  1. Advanced bladder cancer: status of first-line chemotherapy and the search for active agents in the second-line setting.

    PubMed

    Gallagher, David J; Milowsky, Matthew I; Bajorin, Dean F

    2008-09-15

    Urothelial carcinoma (UC) remains a significant health problem affecting an estimated 68,810 people in 2008 alone in the US. The majority of patients with metastatic disease develop disease recurrence, and long-term survival rates are poor. There is no standard of care for the treatment of patients with UC after the failure of cisplatin-based regimens in the first-line setting. Efforts to improve second-line treatment have led to the evaluation of single agents such as vinflunine and pemetrexed, and multidrug combinations with cytotoxic and targeted agents, including trastuzumab and bevacizumab. The authors reviewed the activity of several single agents and combination regimens in patients with UC. Emerging strategies for the measurement of response in clinical trials were also outlined.

  2. Is whole gland salvage cryotherapy effective as palliative treatment of haematuria in patients with locally advanced prostate cancer? Results of a preliminary case series

    PubMed Central

    Mucciardi, Giuseppe; Galì, Alessandro; Pappalardo, Rosa; Lembo, Francesco; Anastasi, Giuseppina; Butticè, Salvatore; Ascenti, Giorgio; Lugnani, Franco

    2015-01-01

    Objectives: Locally advanced prostate cancer may cause several complications such as haematuria, bladder outlet obstruction, and renal failure due to the ureteral obstruction. Various treatments have been suggested, including radiotherapy, antifibrinolytics, bladder irrigation with alum solution, transurethral surgery and angioembolization, none of which have proven effectiveness. In the last years cryoablation has become a valid therapeutic option for prostate cancer. In our experience we used this ‘new’ technique as haemostatic therapy. Methods: We selected four patients with gross haematuria affected by locally advanced hormone refractory prostate cancer, who had already been treated with primary radiotherapy. We used third-generation cryotherapy: under ultrasonographic guidance, we inserted six cryoprobes, two in each of the vascular pedicles reaching at least −60°C, and three thermometers. We then induced two freeze–thaw cycles. Results: After the operation the haematuria stopped in all patients and at 9-month follow up we observed a mean of four red cells (range three to five) in the urinary sediment with no evidence of bacteriuria. Prostate volume, prostate-specific antigen and postmicturition residue were significantly reduced. Qmax improved significantly too. Conclusion: Our experience has given us good results with minimal intra- and postoperative complications. We think that haemostatic cryotherapy as a palliative approach for locally advanced prostate cancer could represent a valid treatment option and more consideration could be given to its use. PMID:26425138

  3. Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings.

    PubMed

    Phillips, Andrew; Cambiano, Valentina; Nakagawa, Fumiyo; Mabugu, Travor; Magubu, Travor; Miners, Alec; Ford, Debbie; Pillay, Deenan; De Luca, Andrea; Lundgren, Jens; Revill, Paul

    2014-01-01

    To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations being identified. An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa. Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted outcomes were assessed over 2015-2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used. The most effective strategy, in terms of DALYs averted, was one using viral load monitoring without confirmation. The incremental cost-effectiveness ratio for this strategy was $2113 (the same as that for viral load monitoring with confirmation). ART monitoring strategies which involved resistance testing did not emerge as being more effective or cost effective than strategies not using it. The slightly reduced ART costs resulting from use of resistance testing, due to less use of second line regimens, was of similar magnitude to the costs of resistance tests. Use of resistance testing at the time of first line failure as part of the decision whether to switch to second line therapy was not cost-effective, even though the test was assumed to be very inexpensive.

  4. Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients

    PubMed Central

    Kim, Min Kyoung; Ahn, Jin Hee; Lee, Soon Im; Ahn, Sei-Hyun; Son, Byung Ho; Gong, Gyungyub; Kim, Hak-Hee; Lee, Jung-Shin; Kang, Yoon-Koo; Kim, Woo Kun

    2006-01-01

    Purpose To evaluate the efficacy of gemcitabine-based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2nd-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and gemcitabine/capecitabine (GX). Materials and Methods Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively. Results The median number of prior metastatic chemotherapy regimens was 2 (range 0~4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5~9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0~4.2 months). Compared with monotherapy (G), com - bination therapy with vinorelbine or capecitabine (GV/GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival. Conclusions The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2nd-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients. PMID:19771244

  5. Partner-based adherence intervention for second-line antiretroviral therapy (ACTG A5234): a multinational randomised trial.

    PubMed

    Gross, Robert; Zheng, Lu; La Rosa, Alberto; Sun, Xin; Rosenkranz, Susan L; Cardoso, Sandra Wagner; Ssali, Francis; Camp, Rob; Godfrey, Catherine; Cohn, Susan E; Robbins, Gregory K; Chisada, Anthony; Wallis, Carole L; Reynolds, Nancy R; Lu, Darlene; Safren, Steven A; Hosey, Lara; Severe, Patrice; Collier, Ann C

    2015-01-01

    Adherence is key to the success of antiretroviral therapy. Enhanced partner support might benefit patients with previous treatment failure. We aimed to assess whether an enhanced partner-based support intervention with modified directly observed therapy would improve outcomes with second-line therapy in HIV-infected patients for whom first-line therapy had failed. We did a multicentre, international, randomised clinical trial at nine sites in Botswana, Brazil, Haiti, Peru, South Africa, Uganda, Zambia, and Zimbabwe. Participants aged 18 years or older for whom first-line therapy had failed, with HIV RNA concentrations greater than 1000 copies per mL and with a willing partner, were randomly assigned (1:1), via computer-generated randomisation, to receive partner-based modified directly observed therapy or standard of care. Randomisation was stratified by screening HIV RNA concentration (≤10 000 copies per mL vs >10 000 copies per mL). Participants and site investigators were not masked to group assignment. Primary outcome was confirmed virological failure (viral load >400 copies per mL) by week 48. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00608569. Between April 23, 2009, and Sept 29, 2011, we randomly assigned 259 participants to the modified directly observed therapy group (n=129) or the standard-of-care group (n=130). 34 (26%) participants in the modified directly observed therapy group achieved the primary endpoint of virological failure by week 48 compared with 23 (18%) participants in the standard-of-care group. The Kaplan-Meier estimated cumulative probability of virological failure by week 48 was 25·1% (95% CI 17·7-32·4) in the modified directly observed therapy group and 17·3% (10·8-23·7) in the standard-of-care group, for a weighted difference in standard of care versus modified directly observed therapy of -6·6% (95% CI -16·5% to 3·2%; p=0·19). 36 (14%) participants reported at least

  6. First- and Second-Line Bevacizumab in Addition to Chemotherapy for Metastatic Colorectal Cancer: A United States–Based Cost-Effectiveness Analysis

    PubMed Central

    Goldstein, Daniel A.; Chen, Qiushi; Ayer, Turgay; Howard, David H.; Lipscomb, Joseph; El-Rayes, Bassel F.; Flowers, Christopher R.

    2015-01-01

    Purpose The addition of bevacizumab to fluorouracil-based chemotherapy is a standard of care for previously untreated metastatic colorectal cancer. Continuation of bevacizumab beyond progression is an accepted standard of care based on a 1.4-month increase in median overall survival observed in a randomized trial. No United States–based cost-effectiveness modeling analyses are currently available addressing the use of bevacizumab in metastatic colorectal cancer. Our objective was to determine the cost effectiveness of bevacizumab in the first-line setting and when continued beyond progression from the perspective of US payers. Methods We developed two Markov models to compare the cost and effectiveness of fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab in the first-line treatment and subsequent fluorouracil, leucovorin, and irinotecan with or without bevacizumab in the second-line treatment of metastatic colorectal cancer. Model robustness was addressed by univariable and probabilistic sensitivity analyses. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Results Using bevacizumab in first-line therapy provided an additional 0.10 QALYs (0.14 life-years) at a cost of $59,361. The incremental cost-effectiveness ratio was $571,240 per QALY. Continuing bevacizumab beyond progression provided an additional 0.11 QALYs (0.16 life-years) at a cost of $39,209. The incremental cost-effectiveness ratio was $364,083 per QALY. In univariable sensitivity analyses, the variables with the greatest influence on the incremental cost-effectiveness ratio were bevacizumab cost, overall survival, and utility. Conclusion Bevacizumab provides minimal incremental benefit at high incremental cost per QALY in both the first- and second-line settings of metastatic colorectal cancer treatment. PMID:25691669

  7. First- and second-line bevacizumab in addition to chemotherapy for metastatic colorectal cancer: a United States-based cost-effectiveness analysis.

    PubMed

    Goldstein, Daniel A; Chen, Qiushi; Ayer, Turgay; Howard, David H; Lipscomb, Joseph; El-Rayes, Bassel F; Flowers, Christopher R

    2015-04-01

    The addition of bevacizumab to fluorouracil-based chemotherapy is a standard of care for previously untreated metastatic colorectal cancer. Continuation of bevacizumab beyond progression is an accepted standard of care based on a 1.4-month increase in median overall survival observed in a randomized trial. No United States-based cost-effectiveness modeling analyses are currently available addressing the use of bevacizumab in metastatic colorectal cancer. Our objective was to determine the cost effectiveness of bevacizumab in the first-line setting and when continued beyond progression from the perspective of US payers. We developed two Markov models to compare the cost and effectiveness of fluorouracil, leucovorin, and oxaliplatin with or without bevacizumab in the first-line treatment and subsequent fluorouracil, leucovorin, and irinotecan with or without bevacizumab in the second-line treatment of metastatic colorectal cancer. Model robustness was addressed by univariable and probabilistic sensitivity analyses. Health outcomes were measured in life-years and quality-adjusted life-years (QALYs). Using bevacizumab in first-line therapy provided an additional 0.10 QALYs (0.14 life-years) at a cost of $59,361. The incremental cost-effectiveness ratio was $571,240 per QALY. Continuing bevacizumab beyond progression provided an additional 0.11 QALYs (0.16 life-years) at a cost of $39,209. The incremental cost-effectiveness ratio was $364,083 per QALY. In univariable sensitivity analyses, the variables with the greatest influence on the incremental cost-effectiveness ratio were bevacizumab cost, overall survival, and utility. Bevacizumab provides minimal incremental benefit at high incremental cost per QALY in both the first- and second-line settings of metastatic colorectal cancer treatment. © 2015 by American Society of Clinical Oncology.

  8. Laser Science and Limb Salvage.

    PubMed

    Friedman, Steven G

    2011-12-01

    Harnessing light energy in the form of lasers became possible after the discovery of electricity. Scientists found various uses for lasers beginning in the 1960s. Creating large amounts of pulsed UV light with any device, including a laser, remained difficult until excimer lasers were invented in the following decade. The invention of excimer lasers coincided with the advent of balloon angioplasty, leading physicians to speculate about using laser energy to obliterate obstructing arterial lesions. The first report of laser energy to vaporize an atherosclerotic plaque appeared in 1980. The ensuing decades witnessed dramatic refinements of laser fibers, laser energy sources, and catheter delivery systems. The favorable results achieved with excimer laser angioplasty in the early 2000s led to a renewed interest in this technology and to the current widespread use of these devices to treat peripheral as well as coronary artery disease. This paper provides a review of laser energy principles, traces the history of the use of lasers to treat vascular disease, and reviews the current literature pertaining to laser angioplasty and limb salvage.

  9. Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

    PubMed Central

    Rimassa, Lorenza; Abbadessa, Giovanni; Personeni, Nicola; Porta, Camillo; Borbath, Ivan; Daniele, Bruno; Salvagni, Stefania; Van Laethem, Jean-Luc; Van Vlierberghe, Hans; Trojan, Jörg; De Toni, Enrico N.; Weiss, Alan; Miles, Steven; Gasbarrini, Antonio; Lencioni, Monica; Lamar, Maria E.; Wang, Yunxia; Shuster, Dale; Schwartz, Brian E.; Santoro, Armando

    2016-01-01

    ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials. PMID:27579536

  10. The prognostic value of D-dimer levels in metastatic osteosarcoma patients treated with second-line chemotherapy

    PubMed Central

    Sun, Yuanjue; Zhang, Jianjun; Yao, Yang; He, Aina

    2016-01-01

    We performed a retrospective analysis of 32 metastatic osteosarcoma cases to examine the prognostic value of the plasma D-dimer level. We assessed the D-dimer level before second-line chemotherapy (D1) and the D-dimer level after two cycles of second-line chemotherapy (D2). The change in D-dimer level (ΔD) was defined as D2 minus D1. The overall survival (OS) of patients with a high D1 was significantly shorter than those with a low D1 (median OS, 4.7 vs. 16.2 months, P=0.001). Similar results were observed for the D2 (median OS, 4.7 vs. 8.6 months, P=0.033). Multivariable analysis demonstrated that a high D1 (hazard ratio, 3.375; 95% confidence interval, 1.133–10.053; P=0.029) was an unfavorable independent prognostic factor. The mean D2 of 11 patients with stable disease decreased by 0.69 mg/mL compared to the D1 (P = 0.016). The mean D2 increased by 1.47 mg/mL compared to the D1 in 21 patients with progressive disease (P = 0.004). The data suggest that D-dimer may serve as a prognostic biomarker for metastatic osteosarcoma patients treated with second-line chemotherapy. PMID:27564105

  11. Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen.

    PubMed

    De Luca, Andrea; Flandre, Philippe; Dunn, David; Zazzi, Maurizio; Wensing, Annemarie; Santoro, Maria Mercedes; Günthard, Huldrych F; Wittkop, Linda; Kordossis, Theodoros; Garcia, Federico; Castagna, Antonella; Cozzi-Lepri, Alessandro; Churchill, Duncan; De Wit, Stéphane; Brockmeyer, Norbert H; Imaz, Arkaitz; Mussini, Cristina; Obel, Niels; Perno, Carlo Federico; Roca, Bernardino; Reiss, Peter; Schülter, Eugen; Torti, Carlo; van Sighem, Ard; Zangerle, Robert; Descamps, Diane

    2016-05-01

    The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV-1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27% and raltegravir or maraviroc or enfuvirtide in 53%. The prediction model included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R(2) = 0.47 [average squared error (ASE) = 0.67, P < 10(-6)]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our final model outperformed models with existing interpretation systems in both training and validation sets. A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Cost-effectiveness of sorafenib compared to best supportive care in second line renal cell cancer from a payer perspective in Cyprus.

    PubMed

    Petrou, Panagiotis Ke; Talias, Michael A

    2014-02-01

    The objective of this study is to assess the cost effectiveness of sorafenib as a second line treatment of advanced renal cell carcinoma compared to standard best supportive care (BSC) in Cyprus. A probabilistic Decision analytic Markov Model was created to simulate disease progression and data from landmark trials were used. Actual local costs were set according to current guidelines in Cyprus. The incremental cost per quality adjusted life year of sorafenib versus BSC was €102,059. The probability of sorafenib to be cost effective at the threshold of €60,000 was 0%. Total costs were sensitive to the price of product, its effectiveness and to a lesser degree to the utility values. Sorafenib demonstrated superior clinical effectiveness compared to BSC, but it's not cost effective under current willingness to pay threshold. Its orphan status along with solidarity principle may justify reimbursement on an individual patient basis.

  13. SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives

    PubMed Central

    Gurgle, Holly E; White, Karen; McAdam-Marx, Carrie

    2016-01-01

    Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM) who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium–glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient. PMID:27350752

  14. Trial-Based Cost-Utility Analysis of Icotinib versus Gefitinib as Second-Line Therapy for Advanced Non-Small Cell Lung Cancer in China.

    PubMed

    Zhang, Chunxiang; Zhang, Hongmei; Shi, Jinning; Wang, Dong; Zhang, Xiuwei; Yang, Jian; Zhai, Qizhi; Ma, Aixia

    2016-01-01

    Our objective is to compare the cost-utility of icotinib and gefitinib for the second-line treatment of advanced non-small cell lung cancer (NSCLC) from the perspective of the Chinese healthcare system. Model technology was applied to assess the data of randomized clinical trials and the direct medical costs from the perspective of the Chinese healthcare system. Five-year quality-adjusted life years (QALYs) and incremental cost-utility ratios (ICURs) were calculated. One-way and probabilistic sensitivity analyses (PSA) were performed. Our model suggested that the median progression-free survival (PFS) was 4.2 months in the icotinib group and 3.5 months in the gefitinib group while they were 4.6 months and 3.4 months, respectively, in the trials. The 5-year QALYs was 0.279 in the icotinib group and 0.269 in the gefitinib group, and the according medical costs were $10662.82 and $13127.57. The ICUR/QALY of icotinib versus gefitinib presented negative in this study. The most sensitive parameter to the ICUR was utility of PFS, ranging from $-1,259,991.25 to $-182,296.61; accordingly the icotinib treatment consistently represented a dominant cost-utility strategy. The icotinib strategy, as a second-line therapy for advanced NSCLC patients in China, is the preferred strategy relative to gefitinib because of the dominant cost-utility. In addition, icotinib shows a good curative effect and safety, resulting in a strong demand for the Chinese market.

  15. Cost Effectiveness Analysis of Different Management Strategies between Best Supportive Care and Second-line Chemotherapy for Platinum-resistant or Refractory Ovarian Cancer.

    PubMed

    Luealon, Phanida; Khempech, Nipon; Vasuratna, Apichai; Hanvoravongchai, Piya; Havanond, Piyalamporn

    2016-01-01

    There is no standard treatment for patients with platinum-resistant or refractory epithelial ovarian cancer. Single agent chemotherapies have evidence of more efficacy and less toxicity than combination therapy. Most are very expensive, with appreciable toxicity and minimal survival. Since it is difficult to make comparison between outcomes, economic analysis of single-agent chemotherapy regimens and best supportive care may help to make decisions about an appropriate management for the affected patients. To evaluate the cost effectiveness of second-line chemotherapy compared with best supportive care for patients with platinum-resistant or refractory epithelial ovarian cancer. A Markov model was used to estimate the effectiveness and total costs associated with treatments. The hypothetical patient population comprised women aged 55 with platinum-resistant or refractory epithelial ovarian cancer. Four types of alternative treatment options were evaluated: 1) gemcitabine followed by BSC; 2) pegylated liposomal doxorubicin (PLD) followed by BSC; 3) gemcitabine followed by topotecan; and 4) PLD followed by topotecan. Baseline comparator of alternative treatments was BSC. Time horizon of the analysis was 2 years. Health care provider perspective and 3% discount rate were used to determine the costs of medical treatment in this study. Quality-adjusted life-years (QALY) were used to measure the treatment effectiveness. Treatment effectiveness data were derived from the literature. Costs were calculated from unit cost treatment of epithelial ovarian cancer patients at various stages of disease in King Chulalongkorn Memorial Hospital (KCMH) in the year 2011. Parameter uncertainty was tested in probabilistic sensitivity analysis by using Monte Carlo simulation. One-way sensitivity analysis was used to explore each variable's impact on the uncertainty of the results. Approximated life expectancy of best supportive care was 0.182 years and its total cost was 26,862 Baht. All

  16. Salvage penile curvature correction surgery.

    PubMed

    Hsieh, Cheng-Hsing; Chen, Heng-Shuen; Lee, Wen-Yuan; Chen, Kuo-Liang; Chang, Chao-Hsiang; Hsu, Geng-Long

    2010-01-01

    It is commonly believed that coarser suture materials should be used to provide sufficient tenacity in surgery for penile curvature correction. We report our 15-year experience of fine sutures in a second operation in 31 patients who underwent prior curvature correction elsewhere with coarser sutures, resulting in recurrent penile curvature. Suture materials used in prior surgeries in these patients were either 2-0 or 3-0 nylon sutures. In this series, all 31 patients underwent a modified Nesbit procedure at the level of the collagen bundles using finer sutures. Prior to July 1998, 10 men underwent salvage surgery using 4-0 polyglactin sutures. Thereafter, we adapted 6-0 nylon sutures for another 21 patients. We categorized the patients into the polyglactin (n = 10) and nylon (n = 21) groups respectively. Overall, 29 patients were available for follow-up while using the abridged 5-item version of the International Index of Erectile Function (IIEF-5) scoring system, with 21 patients in the nylon group. We have found cavernosography a practical and reliable method to objectively assess penile morphology in these patients. The penile morphology both subjectively and objectively was excellent in all patients, except for 1 in each group. Erectile function restoration showed a trend of satisfaction in the polyglactin group and based on IIEF-5 was significantly improved in the nylon group (14.2 ± 3.6 vs 21.9 ± 2.1, n = 20, P < .001). These results suggest that in penile tunical surgery, fine sutures such as 6-0 nylon may result in better penile morphology and functional outcomes.

  17. Salvage Lymph Node Dissection for Node-only Recurrence of Prostate Cancer: Ready for Prime Time?

    PubMed

    Suardi, Nazareno; Briganti, Alberto; Gandaglia, Giorgio; Fossati, Nicola; Montorsi, Francesco

    2016-12-30

    Several studies show that salvage lymph-node dissection for node-only recurrence of prostate cancer after radical treatment might represent a viable treatment modality for node-only recurrent PCa. However, as long as high quality data is not available, this approach should still be considered experimental.

  18. The efficacy of salvage logging in reducing subsequent fire severity in conifer-dominated forests of Minnesota, USA

    USGS Publications Warehouse

    Fraver, S.; Jain, T.; Bradford, J.B.; D'Amato, A.W.; Kastendick, D.; Palik, B.; Shinneman, D.; Stanovick, J.

    2011-01-01

    Although primarily used to mitigate economic losses following disturbance, salvage logging has also been justified on the basis of reducing fire risk and fire severity; however, its ability to achieve these secondary objectives remains unclear. The patchiness resulting from a sequence of recent disturbances-blowdown, salvage logging, and ildfire- provided an excellent opportunity to assess the impacts of blowdown and salvage logging on wildfire severity. We used two fire-severity assessments (tree-crown and forest-floor characteristics) to compare post-wildfire conditions among three treatment combinations (Blowdown-Salvage-Fire, Blowdown-Fire, and Fire only). Our results suggest that salvage logging reduced the intensity (heat released) of the subsequent fire. However, its effect on severity (impact to the system) differed between the tree crowns and forest floor: tree-crown indices suggest that salvage logging decreased fire severity (albeit with modest statistical support), while forest-floor indices suggest that salvage logging increased fire severity. We attribute the latter finding to the greater exposure of mineral soil caused by logging operations; once exposed, soils are more likely to register the damaging effects of fire, even if fire intensity is not extreme. These results highlight the important distinction between fire intensity and severity when formulating post-disturbance management prescriptions. ?? 2011 by the Ecological Society of America.

  19. Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study.

    PubMed

    Wessalowski, Rüdiger; Schneider, Dominik T; Mils, Oliver; Friemann, Verena; Kyrillopoulou, Olga; Schaper, Jörg; Matuschek, Christiane; Rothe, Karin; Leuschner, Ivo; Willers, Reinhart; Schönberger, Stefan; Göbel, Ulrich; Calaminus, Gabriele

    2013-08-01

    Although the survival of children and adolescents with malignant germ-cell tumours has improved greatly in recent years, the outcome remains poor for those with refractory or recurrent malignant germ-cell tumours. We aimed to determine whether objective tumour response could be achieved in patients with refractory or recurrent malignant germ-cell tumours with PEI-regional deep hyperthermia as salvage treatment. Patients with refractory or recurrent non-testicular malignant germ-cell tumours after standard cisplatin-based chemotherapy were treated prospectively with PEI chemotherapy (cisplatin 40 mg/m(2), delivered intravenously on days 1 and 4; etoposide 100 mg/m(2), intravenously on days 1-4; and ifosfamide 1800 mg/m(2), intravenously on days 1-4) plus simultaneous 1-h regional deep hyperthermia (41-43°C) on days 1 and 4. Patients received three to four treatment courses at 21-day intervals until residual tumour resection was possible; they subsequently received one or two additional courses of PEI-regional deep hyperthermia. Local radiotherapy was given for incompletely resected tumours. Chemotherapy and hyperthermia toxic effects were assessed using WHO grading. The primary endpoint was the proportion of patients who had an objective response as assessed with Response Evaluation Criteria in Solid Tumors version 1.0 guidelines. Secondary endpoints were the event-free survival and overall survival after 5 years. This ongoing PEI-regional deep hyperthermia study (Hyper-PEI protocol) is registered at the German Cancer Society, number 50-2732. 44 patients aged 7 months to 21 years (median 2 years 7 months) with refractory or recurrent malignant germ-cell tumours (nine patients with poor response, 23 patients with first relapse, 12 patients with multiple relapses) were included in this study. We identified 34 yolk sac tumours, eight embryonal carcinomas, one choriocarcinoma, and one dysgerminoma by histology analysis. Of the 35 patients who had sufficient clinical

  20. Prognostic factors for salvage endoscopic resection for esophageal squamous cell carcinoma after chemoradiotherapy or radiotherapy alone

    PubMed Central

    Kondo, Shinya; Tajika, Masahiro; Tanaka, Tsutomu; Kodaira, Takeshi; Mizuno, Nobumasa; Hara, Kazuo; Hijioka, Susumu; Imaoka, Hiroshi; Goto, Hidemi; Yamao, Kenji; Niwa, Yasumasa

    2016-01-01

    Background and study aims: Endoscopic resection is one treatment option for residual or locally recurrent esophageal cancer after definitive chemoradiotherapy or radiotherapy alone. However, little is known about the clinical benefit of salvage endoscopic resection for these lesions. Therefore, the effectiveness and prognostic factors of salvage endoscopic resection were investigated. Patients and methods: A total of 37 patients with esophageal squamous cell carcinoma (SCC) who underwent salvage endoscopic resection after definitive chemoradiotherapy or radiotherapy alone were reviewed. The method of salvage endoscopic resection was endoscopic mucosal resection using a cap (EMR-C), strip biopsy, or endoscopic submucosal dissection. The effectiveness and prognostic factors of salvage endoscopic resection were retrospectively analyzed. Results: A total of 37 patients with 49 lesions underwent salvage endoscopic resection. Baseline clinical stages were I in 23 patients, II in 3 patients, III in 9 patients, and IV in 2 patients. The number of locoregional recurrences and residual lesions were 35 and 14, respectively. The curative en bloc resection rate was 53.1 % (26/49). The total incidence of complications was 18.9 % (7/37); all were successfully managed conservatively. The 3-year and 5-year overall survival rates were 72.9 % and 53.3 %, respectively, with a median follow-up period of 54 months. Baseline clinical T1 – 2 and N0 were significant factors for good prognosis in terms of overall survival on univariate analysis. Conclusions: Salvage endoscopic resection, especially EMR-C, is a safe and feasible procedure to control residual or recurrent superficial esophageal SCC after definitive chemoradiotherapy or radiotherapy alone. The present results showed that baseline clinical T1 – 2 and N0 before chemoradiotherapy or radiotherapy were significant prognostic factors. PMID:27540571

  1. Lower limb salvage surgery using Ilizarov circular external frame for a landmine injury about the knee.

    PubMed

    Demiralp, Bahtiyar; Yıldırım, Cengiz; Yurttaş, Yüksel; Çiçek, Engin Ilker; Başbozkurt, Mustafa

    2013-01-01

    Limb salvage for severe trauma has been replaced amputation as the primary treatment in many trauma centers. However, the long-term outcomes after limb reconstruction or amputation have not been fully evaluated. In this report, we present the treatment results of limb salvage surgery using Ilizarov external circular frame in a male case who had a-22-cm bone loss on the left distal femur and left proximal tibia and large soft tissue defect around the knee due to stepping on a landmine with his knee. The decision to amputate a severely injured limb, being irreversible, is challenging and significantly affects the body image and the patient. Extremity salvage surgery should be considered initially when evaluating patients with high-energy injured limbs at high risk for amputation.

  2. Second-line pazopanib in patients with relapsed and refractory small-cell lung cancer: a multicentre phase II study of the Hellenic Oncology Research Group.

    PubMed

    Koinis, F; Agelaki, S; Karavassilis, V; Kentepozidis, N; Samantas, E; Peroukidis, S; Katsaounis, P; Hartabilas, E; Varthalitis, I I; Messaritakis, I; Fountzilas, G; Georgoulias, V; Kotsakis, A

    2017-06-27

    Pazopanib is a tyrosine kinase inhibitor with antiangiogenic activity. Vascular endothelial growth factor expression is increased in SCLC and is correlated with poor prognosis. The efficacy and tolerance of second-line pazopanib in SCLC was evaluated. Patients with platinum-sensitive (cohort A; n=39) and -resistant/refractory (cohort B; n=19) SCLC were enrolled in a multicentre phase II study. The primary end point was the progression-free survival rate (PFS-R) at week 8 in each cohort. Pazopanib (800 mg per day per os) was administered until progressive disease (PD). Circulating tumour cells (CTCs) were enumerated using the Cellsearch assay. All patients were evaluable for response and toxicity. In the intention-to-treat analysis, eight (13.8%) patients achieved partial response (PR) (95% confidence interval (CI): 5.0-22.7), 20 (34.5%) stable disease (SD) and 30 (51.7%) PD. Accrual in cohort B was halted because the hard-stop rule was met; in cohort A, the PFS-R was 59% (95% CI: 43.5-74.4; PR=7, SD=16). Nine (23.1%) patients received pazopanib for >6 months and 3 of them for >12 months. One pazopanib cycle resulted to a significant decrease to the number of patients with ⩾5 CTCs/7.5 ml of blood (20%) compared with baseline (50%). The median PFS and OS for all patients was 2.5 months (95% CI: 1.9-3.1 months) and 6.0 months (95% CI: 3.8-8.2 months), respectively (cohort A: PFS=3.7 months and OS=8.0 months). No unexpected toxicity was observed. Second-line treatment with pazopanib in platinum-sensitive SCLC is well tolerated and resulted in promising objective responses and disease control; CTC enumeration might serve as a reliable surrogate biomarker of response.

  3. Viremia and HIV-1 drug resistance mutations among patients receiving second-line highly active antiretroviral therapy in Chennai, Southern India.

    PubMed

    Saravanan, Shanmugam; Vidya, Madhavan; Balakrishnan, Pachamuthu; Kantor, Rami; Solomon, Sunil S; Katzenstein, David; Kumarasamy, Nagalingeswaran; Yeptomi, Tokugha; Sivamalar, Sathasivam; Rifkin, Samara; Mayer, Kenneth H; Solomon, Suniti

    2012-04-01

    A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (interquartile range, 169-1 997 967). Sequencing was done for 107 samples with PVLs >2000 copies/mL: 33 patients (73%) had 1 of the protease (PR) inhibitor mutations; 41 (91%) had nucleoside reverse-transcriptase inhibitor (NRTI) mutations; 33 (73%) had non-NRTI (NNRTI) mutations; and 30 (66.7%) had both NRTI and NNRTI mutations. Triple-class resistance to NRTIs, NNRTIs, and PR inhibitors was observed in 24 (53%) patients. Based on the mutational profiles observed, all 45 sequences were susceptible to darunavir and tipranavir, whereas 47% showed resistance to lopinavir, 58% showed resistance to atazanavir, and >60% showed resistance to saquinavir, indinavir, nelfinavir, and fosamprenavir. The results of the study showed that the majority of patients receiving second-line antiretroviral therapy started to accumulate PR resistance mutations, and the mutation profiles suggest that darunavir might be the drug of choice for third-line regimens in India.

  4. Viremia and HIV-1 Drug Resistance Mutations Among Patients Receiving Second-Line Highly Active Antiretroviral Therapy in Chennai, Southern India

    PubMed Central

    Vidya, Madhavan; Balakrishnan, Pachamuthu; Kantor, Rami; Solomon, Sunil S.; Katzenstein, David; Kumarasamy, Nagalingeswaran; Yeptomi, Tokugha; Sivamalar, Sathasivam; Rifkin, Samara; Mayer, Kenneth H.; Solomon, Suniti

    2012-01-01

    Background. A cross-sectional study among individuals receiving second-line antiretroviral treatment was conducted to report on the level of detectable viremia and the types of drug resistance mutations among those with detectable human immunodeficiency virus (HIV) type 1 plasma viral loads (PVLs). Methods. PVLs were measured using Abbott m2000rt real-time polymerase chain reaction, and genotyping was performed with the ViroSeq genotyping system, version 2.0, and ViroSeq analysis software, version 2.8. Results. Of 107 patient plasma specimens consecutively analyzed, 30 (28%) had undetectable PVLs (<150 copies/mL), and 77 (72%) were viremic with a median PVL of 5450 copies/mL (