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Sample records for chemotherapy agent thiotepa

  1. Chemotherapy drug thioTEPA exacerbates stress-induced anhedonia and corticosteroid responses but not impairment of hippocampal cell proliferation in adult mice.

    PubMed

    Wilson, Courtney L; Weber, E Todd

    2013-01-01

    Cancer patients often suffer long-lasting affective and cognitive impairments as a result of chemotherapy treatment. Previous work in our lab has shown deficits in learning and memory and hippocampal cell proliferation in mice lasting up to 20 weeks following acute administration of thioTEPA. In this study, the effects of thioTEPA in conjunction with effects of chronic stress on depression-related behavior were examined in C57BL/6J mice, 12 weeks following thioTEPA administration. Chemotherapy-treated mice showed a diminished sucralose preference compared to controls that was further exacerbated after 2 weeks of daily restraint stress. This intensifying effect was not observed in the Porsolt forced swim test. Moreover, stress-induced corticosteroid responses were exaggerated in thioTEPA-treated mice. Cell proliferation in the dentate gyrus of the hippocampus was also impaired similarly by prior thioTEPA treatment and by daily restraint stress, with no additive effect. Results suggest that some depression-related impairments may be exacerbated by chemotherapy treatment through altered corticosteroid regulation. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Chemotherapy drug thioTEPA exacerbates stress-induced anhedonia and corticosteroid responses but not impairment of hippocampal cell proliferation in adult mice

    PubMed Central

    Wilson, Courtney L.; Weber, E. Todd

    2012-01-01

    Cancer patients often suffer long-lasting affective and cognitive impairments as a result of chemotherapy treatment. Previous work in our lab has shown deficits in learning and memory and hippocampal cell proliferation in mice lasting up to 20 weeks following acute administration of thioTEPA. In this study, the effects of thioTEPA in conjunction with effects of chronic stress on depression-related behavior were examined in C57BL/6J mice, 12 weeks following thioTEPA administration. Chemotherapy-treated mice showed a diminished sucralose preference compared to controls that was further exacerbated after 2 weeks of daily restraint stress. This intensifying effect was not observed in the Porsolt forced swim test. Moreover, stress-induced corticosteroid responses were exaggerated in thioTEPA-treated mice. Cell proliferation in the dentate gyrus of the hippocampus was also impaired similarly by prior thioTEPA treatment and by daily restraint stress, with no additive effect. Results suggest that some depression-related impairments may be exacerbated by chemotherapy treatment through altered corticosteroid regulation. PMID:22981560

  3. Second allogeneic stem cell transplantation for acute leukemia using a chemotherapy only cytoreduction with clofarabine, melphalan, and thiotepa

    PubMed Central

    Spitzer, Barbara; Perales, Miguel-Angel; Kernan, Nancy A.; Prockop, Susan E.; Zabor, Emily C.; Webb, Nicholas; Castro-Malaspina, Hugo; Papadopoulos, Esperanza B.; Young, James W.; Scaradavou, Andromachi; Kobos, Rachel; Giralt, Sergio A.; O'Reilly, Richard J; Boulad, Farid

    2016-01-01

    Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) remains one of the leading causes of mortality in patients with leukemia. Treatment options in this population remain limited, with concern for both increased toxicity and further relapse. We treated 18 patients with acute leukemia for marrow +/- extramedullary relapse after a prior alloHSCT, with a myeloablative cytoreductive regimen including clofarabine, melphalan, and thiotepa, followed by a second or third transplant (HSCT2/3) from the same or different donor. All patients were in remission at the time of HSCT2/3. All evaluable patients engrafted. The most common toxicity was reversible transaminitis associated with clofarabine. Two patients died from transplant-related causes. Seven patients relapsed post-HSCT2/3 and died of disease. Nine of 18 patients are alive and disease-free, with a three-year 49% probability of overall survival. Patients whose remission duration after initial alloHSCT was >6 months achieved superior outcomes (3-year OS 74%, 95% CI: 53-100%), compared with those relapsing within 6 months (0%), (p<0.001). This new cytoreductive regimen has yielded promising results with acceptable toxicity for second transplants in patients with high-risk ALL and AML who relapsed after a prior transplant, using various graft and donor options,. This approach merits further evaluation in collaborative group studies. PMID:27184623

  4. Toxicity of high-dose chemotherapy with etoposide, thiotepa and CY in treating poor-prognosis Ewing's sarcoma family tumors: the experience of the Bambino Gesù Children's Hospital.

    PubMed

    Ilari, I; De Ioris, M A; Milano, G M; Pessolano, R; De Lurentis, C; De Sio, L; Fidani, P; Jenkner, A; Cozza, R

    2010-08-01

    We report the toxicity of high-dose chemotherapy (HDC) based on etoposide, thiotepa and CY (ETC) in children with poor-prognosis Ewing's sarcoma family tumors (ESFTs). A total of 26 patients with high-risk ESFT (metastasis or axis localization or tumor volume >200 ml or necrosis <95%) were reviewed. The conditioning was based on etoposide (600 mg/m(2)), thiotepa (750 mg/m(2)) and CY (120 mg/kg) followed by autologous BM or PBSC rescue. The conditioning regimen was well tolerated, without any toxic deaths. The median time from transplant to a neutrophil count of >0.5 x 10(9)/l was 10 days (range 6-27) and 22.5 days (range 9-114) for a plt count of >50 x 10(9)/l. Oral mucositis was recorded in 20 patients, grade 1/2 in 19 and grade 3 in the last patient. Diarrhea grade 1/2 was recorded in four patients and grade 1/2 liver toxicity in four patients. Sepsis was documented in four cases and skin toxicity in three. Lung and tubular toxicity, respectively, were reported in one patient each. We conclude that the ETC regimen presented a limited and manageable toxicity. Further studies would confirm the role of ETC in high-risk ESFT.

  5. Pig-a gene mutation and micronucleated reticulocyte induction in rats exposed to tumorigenic doses of the leukemogenic agents chlorambucil, thiotepa, melphalan, and 1,3-propane sultone.

    PubMed

    Dertinger, Stephen D; Phonethepswath, Souk; Avlasevich, Svetlana L; Torous, Dorothea K; Mereness, Jared; Cottom, John; Bemis, Jeffrey C; Macgregor, James T

    2014-05-01

    To evaluate whether blood-based genotoxicity endpoints can provide temporal and dose-response data within the low-dose carcinogenic range that could contribute to carcinogenic mode of action (MoA) assessments, we evaluated the sensitivity of flow cytometry-based micronucleus and Pig-a gene mutation assays at and below tumorigenic dose rate 50 (TD50) levels. The incidence of micronucleated reticulocytes (MN-RET) was used to evaluate chromosomal damage, and the frequency of CD59-negative reticulocytes (RET(CD59-) ) and erythrocytes (RBC(CD59-) ) served as phenotypic reporters of mutation at the X-linked Pig-a gene. Several leukemogenic agents with a presumed genotoxic MoA were studied. Specifically, male Sprague Dawley rats were treated via oral gavage for 28 days with chlorambucil, thiotepa, melphalan, and 1,3-propane sultone at doses corresponding to 0.33x, 1x, and 3x TD50, as well as at the maximum tolerated dose. Frequencies of MN-RET were determined at Days 4 and 29, and RET(CD59-) and RBC(CD59-) data were collected pretreatment as well as Days 15/16, 29, and 56/57. Dose-related increases were observed for each endpoint, and time to maximal effect was consistently: MN-RET < RET(CD59-)  < RBC(CD59-) . For each of the chemicals studied, the genotoxic events occurred long before tumors or preneoplastic lesions would be expected. Furthermore, in the case of Pig-a gene mutation, the responses were observed at or below the TD50 dose for three out of the four chemicals studied. These data illustrate the potential for quantitative blood-based analyses to provide dose-response and temporality information that relates genetic damage to cancer induction.

  6. A comprehensive understanding of thioTEPA metabolism in the mouse using UPLC-ESI-QTOFMS-based metabolomics.

    PubMed

    Li, Fei; Patterson, Andrew D; Höfer, Constance C; Krausz, Kristopher W; Gonzalez, Frank J; Idle, Jeffrey R

    2011-04-15

    ThioTEPA, an alkylating agent with anti-tumor activity, has been used as an effective anticancer drug since the 1950s. However, a complete understanding of how its alkylating activity relates to clinical efficacy has not been achieved, the total urinary excretion of thioTEPA and its metabolites is not resolved, and the mechanism of formation of the potentially toxic metabolites S-carboxymethylcysteine (SCMC) and thiodiglycolic acid (TDGA) remains unclear. In this study, the metabolism of thioTEPA in a mouse model was comprehensively investigated using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based-metabolomics. The nine metabolites identified in mouse urine suggest that thioTEPA underwent ring-opening, N-dechloroethylation, and conjugation reactions in vivo. SCMC and TDGA, two downstream thioTEPA metabolites, were produced from thioTEPA from two novel metabolites 1,2,3-trichloroTEPA (VII) and dechloroethyltrichloroTEPA (VIII). SCMC and TDGA excretion were increased about 4-fold and 2-fold, respectively, in urine following the thioTEPA treatment. The main mouse metabolites of thioTEPA in vivo were TEPA (II), monochloroTEPA (III) and thioTEPA-mercapturate (IV). In addition, five thioTEPA metabolites were detected in serum and all shared similar disposition. Although thioTEPA has a unique chemical structure which is not maintained in the majority of its metabolites, metabolomic analysis of its biotransformation greatly contributed to the investigation of thioTEPA metabolism in vivo, and provides useful information to understand comprehensively the pharmacological activity and potential toxicity of thioTEPA in the clinic.

  7. Rational Choice of Antiemetic Agents during Cancer Chemotherapy

    PubMed Central

    Brigden, Malcolm L.; Wilson, Kenneth S.; Barnett, Jeffrey B.

    1983-01-01

    Nausea and vomiting are major limitations in cancer chemotherapy. Individual susceptibility to nausea varies enormously. There is no ideal antiemetic, but some work with some chemotherapeutic agents, and some are more effective in younger patients. This article describes a flexible, stepped approach using the phenothiazines, metoclopramide, cannabinoids, anticholinergics, antihistamines and others. PMID:21283402

  8. Principles and major agents in clinical oncology chemotherapy

    SciTech Connect

    Weller, R.E.

    1991-10-01

    This paper provides a brief classification of drugs available for veterinary chemotherapy, as well as justifications for their use. Some common neoplasia and the drugs of choice for their treatment are described. A listing by class of systemic chemotherapeutic agents, their mode of action, tumors responsive to the drugs, precautions and common adverse effects and mode of administration is provided. 2 tabs. (MHB)

  9. Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

    PubMed

    Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

    2015-02-01

    Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents.

  10. Rapid desensitization of hypersensitivity reactions to chemotherapy agents.

    PubMed

    Castells, Mariana

    2006-08-01

    All chemotherapy agents can cause hypersensitivity reactions, which have limited the used of critical drugs in very sick patients for fear of inducing a more severe reaction and possibly death. The choice of an alternative chemotherapy regimen is often limited by tumor sensitivity and, because of the increasing number of cancer survivors, exposure to multiple courses of the same or similar chemotherapy agents. Increased exposures lead to sensitization and to hypersensitivity reactions in an increasing patient population. The need to offer first line therapy after cancer recurrence has spurred the clinical development of rapid desensitizations, which allow patients to be treated with medications to which they have presented hypersensitivity reactions. Desensitization protocols are available to treat hypersensitivity reactions to most chemotherapy agents including taxenes, platinums, doxorubicin, monoclonal antibodies and others, by gradual re-introduction of small amounts of drug antigens up to full therapeutic doses. Candidate patients include those who present mild to severe type I hypersensitivity, mast cell/IgE dependent, reactions during the chemotherapy infusion or shortly after. Symptoms include pruritus, flushing, urticaria, angioedema, respiratory and gastrointestinal distress, changes in blood pressure including hypotension, and shock with anaphylaxis. Associated musculoskeletal symptoms and pain can be present in patients reacting to taxenes as in anaphylactoid reactions, in which mast cell/IgE mechanisms cannot be demonstrated. There is now strong evidence that anaphylactoid reactions are amendable to treatment with the same rapid desensitization protocols as for type I hypersensitivity reactions. Initial rapid desensitizations should only be performed in settings with one on one nurse-patient care and where resuscitation personnel and resources are readily available. Temporary tolerization is achieved in a few hours. After the first desensitization

  11. Chemotherapy

    MedlinePlus

    ... the cancer cells. This is called palliative chemotherapy. Chemotherapy for conditions other than cancer Some chemotherapy drugs ... you'll receive. Side effects that occur during chemotherapy treatment Common side effects of chemotherapy drugs include: ...

  12. Antiangiogenic Agents in Combination with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Ulahannan, Susanna V; Brahmer, Julie R

    2011-01-01

    Most patients with non-small cell lung cancer (NSCLC) present with advanced disease requiring systemic chemotherapy. Treatment with the antiangiogenic agent bevacizumab in combination with standard platinum-based doublet chemotherapy has been shown to improve outcomes in patients with advanced NSCLC. Several multitargeted antiangiogenic tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, and axitinib) are also being evaluated in combination with standard chemotherapy. Here we review current clinical data with combination therapy involving antiangiogenic agents and cytotoxic chemotherapy in patients with advanced NSCLC. PMID:21469981

  13. Chemotherapy

    MedlinePlus

    ... during chemotherapy. Chemotherapy is most often given in cycles. These cycles may last 1 day, several days, or a ... period when no chemotherapy is given between each cycle. A rest period may last for days, weeks, ...

  14. Treatment of patients with secondary central nervous system lymphoma with high-dose busulfan/thiotepa-based conditioning and autologous stem cell transplant.

    PubMed

    Oh, Danielle H; Chua, Neil; Street, Lesley; Stewart, Douglas A

    2016-01-01

    Although the survival rates are extremely low for patients with secondary central nervous system lymphoma (SCNSL) treated with conventional chemotherapy and radiotherapy, more encouraging outcomes have recently been reported in small series with high-dose (HD) therapy and autologous stem cell transplant (ASCT). The optimal HD regimen for SCNSL is unknown. Despite reports of thiotepa/busulfan-based conditioning for primary CNS lymphoma, very little data exist regarding the use of this regimen for SCNSL. We analyzed 23 patients with SCNSL (median age 62 years) who underwent ASCT at two Alberta centers using thiotepa, busulfan, cyclophosphamide (TBC) in six patients prior to 2011 and rituximab-busulfan, melphalan, thiotepa (R-BuMelTt) in 17 patients after 2011. At a median follow-up of 27.8 months (4.2-113.6), the 2-year actuarial rate of progression-free survival was 76.1%. In conclusion, our results demonstrate encouraging survival outcomes for patients with SCNSL treated with R-BuMelTt and ASCT.

  15. Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

    PubMed Central

    Lefranc, Florence; Carbone, Marianna; Mollo, Ernesto; Gavagnin, Margherita; Betancourt, Tania; Dasari, Ramesh

    2016-01-01

    Abstract The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity. PMID:27925266

  16. Chemotherapy

    Cancer.gov

    Chemotherapy is a type of cancer treatment that uses drugs to kill cancer cells. Learn how chemotherapy works against cancer, why it causes side effects, and how it is used with other cancer treatments.

  17. Iron Supplementation for Chemotherapy-Induced Anemia in Patients Receiving Erythropoiesis-Stimulating Agents.

    PubMed

    Mhaskar, Rahul; Djulbegovic, Benjamin

    2016-11-01

    What are the benefits and harms of iron supplementation alone and as an adjunct to erythropoiesis-stimulating agents (ESAs) compared with ESA alone in the treatment of chemotherapy-induced anemia? Addition of iron to ESAs improves hematopoietic response, reduces the need for red blood cell transfusions, increases hemoglobin levels, and seems to be well tolerated. The subgroup analyses suggest the superiority of parenteral iron over oral iron supplementation in the treatment of chemotherapy-induced anemia.

  18. Chemotherapy

    MedlinePlus

    ... people. But knowing what chemotherapy is, how it works, and what to expect can often help calm your fears. It can also give you a better sense of control over your cancer treatment. ... Drugs Work CancerQuest: Chemotherapy [video] Interactive Chemotherapy Program from Emmi ...

  19. Management of chemotherapy-induced nausea and vomiting : focus on newer agents and new uses for older agents.

    PubMed

    Navari, Rudolph M

    2013-03-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a serotonin 5-HT3 receptor antagonist, dexamethasone and a neurokinin 1 (NK1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Aprepitant, the first and only agent clinically available in the NK1 receptor antagonist drug class has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone to control CINV. Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US-FDA approved antipsychotic, has emerged in recent trials as an effective preventative agent for CINV, as well as a very effective agent for the treatment of breakthrough emesis and nausea. Clinical trials using gabapentin, cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

  20. Third-line chemotherapy and novel agents for metastatic germ cell tumors.

    PubMed

    Veenstra, Christine M; Vaughn, David J

    2011-06-01

    Although germ cell tumors (GCT) are among the most curable solid tumors, a subset of patients with GCT experience relapse or progression despite appropriate cisplatin-based therapy or first-line salvage therapy. This article describes the molecular mechanisms of cisplatin resistance, outlines single-agent chemotherapy and combination chemotherapy regimens that are active against GCT in the third-line or later setting, discusses the use of drug therapy for treating growing teratoma syndrome and teratoma with malignant transformation, outlines novel agents used to treat GCT, and highlights ongoing clinical trials and future directions in the treatment of refractory GCT. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain - The Cause of Chemo Brain

    DTIC Science & Technology

    2006-11-01

    of Neuronal Birthing in the Brain – The Cause of “Chemo Brain” PRINCIPAL INVESTIGATOR: Robert A Gross, M.D., Ph.D...Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain – The 5a. CONTRACT NUMBER Cause of “Chemo Brain” 5b. GRANT NUMBER DAMD17-03-1...agents that do not (Adriamycin and Taxol) with respect to their ability to impair the birthing of new neurons in the hippocampus of adult mice. By

  2. Managing toxicities associated with antiangiogenic biologic agents in combination with chemotherapy for metastatic colorectal cancer.

    PubMed

    Grenon, Nina N

    2013-08-01

    Toxicities commonly associated with antiangiogenic agents include hypertension, proteinuria, wound-healing complications, bleeding or hemorrhage, thromboembolic events, hypersensitivity reactions, and gastrointestinal perforation; however, toxicities most often attributed to chemotherapy include nausea, vomiting, diarrhea, constipation, fatigue, neuropathy, mucositis, hand-foot syndrome, hypersensitivity reactions, and myelosuppression. Patients with metastatic colorectal cancer (mCRC) who receive an antiangiogenic agent in combination with chemotherapy may experience toxicities related to both chemotherapy and the antiangiogenic agent. If possible, evidence-based interventions should be used for the management of toxicities. Patient education about expected toxicities and optimal toxicity management can promote the optimal use of therapy to improve survival and quality of life. Oncology nurses are well positioned to educate patients and their families on anticipated treatment and management of side effects. This article summarizes the incidence of toxicities associated with the antiangiogenic biologic agents aflibercept and bevacizumab, in combination with chemotherapy for patients with mCRC, and provides strategies for managing these toxicities based on clinical practice guidelines.

  3. Phase I study of temozolomide in combination with thiotepa and carboplatin with autologous hematopoietic cell rescue in patients with malignant brain tumors with minimal residual disease.

    PubMed

    Egan, G; Cervone, K A; Philips, P C; Belasco, J B; Finlay, J L; Gardner, S L

    2016-04-01

    Recurrence of malignant brain tumors results in a poor prognosis with limited treatment options. High-dose chemotherapy with autologous hematopoietic cell rescue (AHCR) has been used in patients with recurrent malignant brain tumors and has shown improved outcomes compared with standard chemotherapy. Temozolomide is standard therapy for glioblastoma and has also shown activity in patients with medulloblastoma/primitive neuro-ectodermal tumor (PNET), particularly those with recurrent disease. Temozolomide was administered twice daily on days -10 to -6, followed by thiotepa 300 mg/m(2) per day and carboplatin dosed using the Calvert formula or body surface area on days -5 to -3, with AHCR day 0. Twenty-seven patients aged 3-46 years were enrolled. Diagnoses included high-grade glioma (n=12); medulloblastoma/PNET (n=9); central nervous system (CNS) germ cell tumor (n=4); ependymoma (n=1) and spinal cord PNET (n=1). Temozolomide doses ranged from 100 mg/m(2) per day to 400 mg/m(2) per day. There were no toxic deaths. Prolonged survival was noted in several patients including those with recurrent high-grade glioma, medulloblastoma and CNS germ cell tumor. Increased doses of temozolomide are feasible with AHCR. A phase II study using temozolomide, carboplatin and thiotepa with AHCR for children with recurrent malignant brain tumors is being conducted through the Pediatric Blood and Marrow Transplant Consortium.

  4. Beyond chemotherapy: new agents for targeted treatment of lymphoma

    PubMed Central

    Younes, Anas

    2011-01-01

    An improved understanding of the molecular biology of cancer cell growth and survival and the role of the microenvironment in supporting the survival of cancer cells, including lymphoma cells, has led to the identification of a number of potential therapeutic targets. Despite these advances, drug development for lymphoma remains slow, inefficient, and frequently unfocused. Future work should focus on identifying `driver' molecular defects of oncogenic pathways that can be targeted therapeutically, discovering predictive biomarkers for treatment response, and prioritizing promising drugs to accelerate their approval. This Review summarizes the current development status of novel agents for lymphoma and discusses strategies to move the field forward. PMID:21151205

  5. Temozolomide single-agent chemotherapy for newly diagnosed anaplastic oligodendroglioma.

    PubMed

    Mikkelsen, T; Doyle, T; Anderson, J; Margolis, J; Paleologos, N; Gutierrez, J; Croteau, D; Hasselbach, L; Avedissian, R; Schultz, L

    2009-03-01

    The treatment of patients with anaplastic oligodendroglioma (AO) has been significantly impacted by the molecular detection of loss of sequences on chromosomes 1p and 19q. We performed a clinical trial to prospectively evaluate the safety of treating patients with AO with temozolomide (TMZ) alone in patients with chromosome 1p/19q loss and with chemo-radiation in patients not harboring this loss. Forty-eight patients were enrolled, 36/48 (75%) with evidence of chromosome 1p/19q loss treated with TMZ alone and 12/18 (25%) without such losses, treated with pre-radiation TMZ followed by chemo-radiation. Despite more aggressive treatment, patients without 1p/19q loss had a shorter progression-free survival (PFS) of 13.5 months. With a median follow-up time of 32 months, patients with 1p/19q LOH had a median TTP of 28.7 months. Patients with AO with 1p/19q LOH can be safely treated with single-agent TMZ and do not appear to experience earlier or more frequent tumor progression. This treatment regimen should be studied as part of a formal randomized clinical trial.

  6. Single-agent Taxane Versus Taxane-containing Combination Chemotherapy as Salvage Therapy for Advanced Urothelial Carcinoma.

    PubMed

    Sonpavde, Guru; Pond, Gregory R; Choueiri, Toni K; Mullane, Stephanie; Niegisch, Guenter; Albers, Peter; Necchi, Andrea; Di Lorenzo, Giuseppe; Buonerba, Carlo; Rozzi, Antonio; Matsumoto, Kazumasa; Lee, Jae-Lyun; Kitamura, Hiroshi; Kume, Haruki; Bellmunt, Joaquim

    2016-04-01

    Single-agent taxanes are commonly used as salvage systemic therapy for patients with advanced urothelial carcinoma (UC). To study the impact of combination chemotherapy delivering a taxane plus other chemotherapeutic agents compared with single-agent taxane as salvage therapy. Individual patient-level data from phase 2 trials of salvage systemic therapy were used. Trials evaluating either single agents (paclitaxel or docetaxel) or combination chemotherapy (taxane plus one other chemotherapeutic agent or more) following prior platinum-based therapy were used. Information regarding the known major baseline prognostic factors was required: time from prior chemotherapy, hemoglobin, performance status, albumin, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of prognostic factors and combination versus single-agent chemotherapy with overall survival (OS). Data were available from eight trials including 370 patients; two trials (n=109) evaluated single-agent chemotherapy with docetaxel (n=72) and cremophor-free paclitaxel (n=37), and six trials (n=261) evaluated combination chemotherapy with gemcitabine-paclitaxel (two trials, with n=99 and n=24), paclitaxel-cyclophosphamide (n=32), paclitaxel-ifosfamide-nedaplatin (n=45), docetaxel-ifosfamide-cisplatin (n=26), and paclitaxel-epirubicin (n=35). On multivariable analysis after adjustment for baseline prognostic factors, combination chemotherapy was independently and significantly associated with improved OS (hazard ratio: 0.60; 95% confidence interval, 0.45-0.82; p=0.001). The retrospective design of this analysis and the trial-eligible population were inherent limitations. Patients enrolled in trials of combination chemotherapy exhibited improved OS compared with patients enrolled in trials of single-agent chemotherapy as salvage therapy for advanced UC. Prospective randomized trials are required to validate a potential role for rational and tolerable combination

  7. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT.

    PubMed

    Sellner, L; Boumendil, A; Finel, H; Choquet, S; de Rosa, G; Falzetti, F; Scime, R; Kobbe, G; Ferrara, F; Delmer, A; Sayer, H; Amorim, S; Bouabdallah, R; Finke, J; Salles, G; Yakoub-Agha, I; Faber, E; Nicolas-Virelizier, E; Facchini, L; Vallisa, D; Zuffa, E; Sureda, A; Dreger, P

    2016-02-01

    Clinical information about thiotepa-based autologous stem cell transplantation (auto-SCT) outside the primary central nervous system lymphoma (PCNSL) field is sparse. In this registry-based retrospective study, we evaluated potential risks and benefits of thiotepa-based preparative regimens compared with BEAM (carmustine, etoposide, cytarabine, melphalan) in auto-SCT for diffuse large B-cell lymphoma (DLBCL, excluding PCNSL), follicular lymphoma (FL) or Hodgkin lymphoma (HL). A total of 14 544 patients (589 thiotepa and 13 955 BEAM) met the eligibility criteria, and 535 thiotepa- and 1031 BEAM-treated patients were matched in a 1:2 ratio for final comparison. No significant differences between thiotepa and BEAM groups for any survival end point were identified in the whole sample or disease entity subsets. For a more detailed analysis, 47 TEAM (thiotepa, etoposide, cytarabine, melphalan)-treated patients were compared with 75 matched BEAM patients with additional collection of toxicity data. Again, there were no significant differences between the two groups for any survival end point. In addition, the frequency of common infectious and non-infectious complications including secondary malignancies was comparable between TEAM and BEAM. These results indicate that thiotepa-based high-dose therapy might be a valuable alternative to BEAM in DLBCL, HL and FL. Further evaluation by prospective clinical trials is warranted.

  8. Nicotinamide Inhibits Alkylating Agent-Induced Apoptotic Neurodegeneration in the Developing Rat Brain

    PubMed Central

    Naseer, Muhammad Imran; Ullah, Ikram; Suh, Joo Won; Kim, Myeong Ok

    2011-01-01

    Background Exposure to the chemotherapeutic alkylating agent thiotepa during brain development leads to neurological complications arising from neurodegeneration and irreversible damage to the developing central nerve system (CNS). Administration of single dose of thiotepa in 7-d postnatal (P7) rat triggers activation of apoptotic cascade and widespread neuronal death. The present study was aimed to elucidate whether nicotinamide may prevent thiotepa-induced neurodegeneration in the developing rat brain. Methodology/Principal Findings Neuronal cell death induced by thiotepa was associated with the induction of Bax, release of cytochrome-c from mitochondria into the cytosol, activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase (PARP-1). Post-treatment of developing rats with nicotinamide suppressed thiotepa-induced upregulation of Bax, reduced cytochrome-c release into the cytosol and reduced expression of activated caspase-3 and cleavage of PARP-1. Cresyl violet staining showed numerous dead cells in the cortex hippocampus and thalamus; post-treatment with nicotinamide reduced the number of dead cells in these brain regions. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) and immunohistochemical analysis of caspase-3 show that thiotepa-induced cell death is apoptotic and that it is inhibited by nicotinamide treatment. Conclusion Nicotinamide (Nic) treatment with thiotepa significantly improved neuronal survival and alleviated neuronal cell death in the developing rat. These data demonstrate that nicotinamide shows promise as a therapeutic and neuroprotective agent for the treatment of neurodegenerative disorders in newborns and infants. PMID:22164206

  9. Primary gastric Hodgkin's lymphoma: favourable outcome following multi-agent chemotherapy without surgical intervention.

    PubMed

    Quintyne, K I; Mulcahy, E; Wallis, F; Wilson, L; Gupta, R K

    2011-02-15

    The authors report the case of a 51-year-old man who presented with left-sided abdominal pain and weight loss associated with drenching night sweats. Preliminary blood tests yielded no specific cause for his symptoms, but abdominal ultrasound revealed multiple hepatic lesions and peripancreatic lymphadenopathy. Further imaging, including positron emission tomography (PET)/CT, revealed fludeoxyglucose 18F (FDG) avid uptake within lymphadenopathy above and below the diaphragm and also noted gastric thickening. Diagnosis was established with gastric biopsy and revealed gastric Hodgkin's lymphoma. He was started on and tolerated multi-agent chemotherapy. Repeated PET/CT and gastric biopsy showed complete metabolic and pathologic response to treatment.

  10. Effects of ethanolamine and choline on thiotepa cellular accumulation and cytotoxicity in L1210 cells

    SciTech Connect

    Egorin, M.J.; Snyder, S.W.; Wietharn, B.E. )

    1990-07-15

    The amino alcohols, ethanolamine and choline, were studied for their effects on (a) L1210 cell growth, (b) N,N{prime},N{double prime}-triethylenetheiphosphoramide (thiotepa)-induced growth inhibition of L1210 cells, and (c) 14C accumulation by L1210 cells incubated with (14C)thiotepa. Ethanolamine, at concentrations up to 300 microM, had no effect on L1210 cell growth but, at concentrations greater than 300 microM, produced a dose-dependent reduction in cell growth. Choline, at concentrations up to 20 mM, had no effect on L1210 cell growth. Neither ethanolamine, at 250 microM, nor choline, at 10 mM, altered the ability of thiotepa to reduce L1210 cell growth. Neither ethanolamine, at 250 microM, nor choline, at 10 mM, affected the rapid phase of 14C accumulation by L1210 cells incubated with (14C)thiotepa. The slow phase of 14C accumulation by L1210 cells incubated with 5 microM (14C)thiotepa, a process which is 80-85% due to production of (14C)phosphatidylethanolamine, was not affected by 250 microM choline. In contrast, ethanolamine produced a dose-dependent reduction in this slow rate of 14C accumulation. The reduction in the slow rate of 14C accumulation produced by ethanolamine was due almost entirely to a decrease in the accumulation of nonexchangeable 14C. Kinetic analysis of the inhibition of 14C accumulation produced by 25, 100, and 250 microM ethanolamine was compatible with competitive inhibition. Thin layer chromatography of cell extracts showed that the ability of ethanolamine to reduce 14C accumulation by L1210 cells incubated with (14C)thiotepa was due solely to reduction in production of (14C)phosphatidylethanolamine. These results are all compatible with and predicted by our previously described scheme wherein thiotepa enters cells by simple diffusion and serves as a prodrug for aziridine.

  11. The use of antioxidant agents for chemotherapy-induced peripheral neuropathy treatment in animal models.

    PubMed

    Carvalho, Larissa F; Silva, Ana Maria F; Carvalho, Adriana A

    2017-10-01

    Antineoplastic drugs such as cisplatin, oxaliplatin, paclitaxel and vincristin are widely used in the treatment of several solid and blood tumours. However, the severity of peripheral neuropathy caused by these agents can affect the patient's quality of life. The major symptoms of chemotherapy-induced peripheral neuropathy (CIPN) involve: sensory loss, paresthesia, dysesthaesia, numbness, tingling, temperature sensitivity, allodynia and hyperalgesia, in a "stocking and glove" distribution. Why many different chemotherapeutic agents result in similar neuropathy profiles is unclear. Many drug classes such as antidepressants, anticonvulsants, antispastic agents and others have been used in clinical practice, but there is no scientific evidence to prove their effectiveness. But drugs as the antioxidant have shown a protective effect against free radical damage. In order to find out a successful treatment for CIPN, animal studies (ie pharmacological and mechanical tests and histopathological immunohistochemical analyses) have been developed to try to determinate the action of the antioxidant agents. This review provides an overview of the major antioxidant agents recently investigated to treat CIPN and the animal models used for this purpose. © 2017 John Wiley & Sons Australia, Ltd.

  12. Chemotherapy

    MedlinePlus

    ... able to change the environment around the cell. Hormones—These substances may interfere with tumor growth by blocking the production of certain proteins in the tumor cells. Mitotic inhibitors—These agents are usually plant-based, natural substances that interfere with the production ...

  13. DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology.

    PubMed

    Cheung-Ong, Kahlin; Giaever, Guri; Nislow, Corey

    2013-05-23

    DNA-damaging agents have a long history of use in cancer chemotherapy. The full extent of their cellular mechanisms, which is essential to balance efficacy and toxicity, is often unclear. In addition, the use of many anticancer drugs is limited by dose-limiting toxicities as well as the development of drug resistance. Novel anticancer compounds are continually being developed in the hopes of addressing these limitations; however, it is essential to be able to evaluate these compounds for their mechanisms of action. This review covers the current DNA-damaging agents used in the clinic, discusses their limitations, and describes the use of chemical genomics to uncover new information about the DNA damage response network and to evaluate novel DNA-damaging compounds.

  14. Treatment of carcinoma in situ of the glans penis with topical chemotherapy agents.

    PubMed

    Alnajjar, Hussain M; Lam, Wayne; Bolgeri, Marco; Rees, Rowland W; Perry, Matthew J A; Watkin, Nicholas A

    2012-11-01

    The use of topical agents in the treatment of carcinoma in situ (CIS) of the penis has been well described in the literature. Previous studies have been limited by small sample size and imprecise end points. Establish the response rate of 5-fluorouracil (5-FU) and imiquimod (IQ) in the treatment of penile CIS in a large contemporary series in a supranetwork centre. Retrospective review of all primary and recurrent cases of penile CIS treated with 5-FU and IQ identified from a prospective database over a 10-yr period. Therapy was standardised in all cases with application to the lesion for 12h every 48 h for 28 d. 5-FU was the first-line therapy, and IQ was the second-line topical agent. The primary end point was defined as complete response (CR; i.e., resolution of lesion), partial response (PR; i.e., lesion reduced in size and or visibility), or no response (NR; ie, no improvement in lesion size and or visibility). The secondary end points included local toxicity and adverse events. No statistical analysis or software was used. A total of 86 patients were diagnosed with CIS of the penis over the 10-yr period. Forty-four (51%) received topical chemotherapy. The mean follow-up was 34 mo. CR to topical chemotherapy was seen in 25 (57%), PR was seen in 6 (13.6%), and NR was seen in the remaining 13 (29.5%) patients. Local toxicity was experienced by 10% of patients, and 12% had an adverse event following application of 5-FU. The retrospective design and short follow-up were the major limitations of this study. Topical chemotherapy agents are moderately effective first-line therapy in the treatment of penile CIS. Toxicity and adverse events were few with our treatment protocol. The issues of long-term surveillance and assessment of partial responders remain a challenge. Topical chemotherapy should remain a first-line treatment option for penile CIS. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  15. The prognostic values of CYP2B6 genetic polymorphisms and metastatic sites for advanced breast cancer patients treated with docetaxel and thiotepa.

    PubMed

    Song, Qingkun; Zhou, Xinna; Yu, Jing; Dong, Ningning; Wang, Xiaoli; Yang, Huabing; Ren, Jun; Lyerly, H Kim

    2015-11-25

    This study investigated interactive effects of CYP2B6 genotypes and liver metastasis on the prognosis of metastatic breast cancer patients who received combined chemotherapy of docetaxel and thiotepa. Totally 153 patients were retrospectively genotyped rs8192719 (c.1294 + 53C > T) and rs2279343 (c.785A > G). Kaplan-Meier method and Cox Proportional Hazard Regression model were used to estimate the survival. Patients with liver metastasis had worsen prognosis, conferring a 2.26-fold high risk of progression and 1.93-fold high risk of death (p < 0.05). Both CT/TT genotype of rs8192719 (c.1294 +  3C > T) and AG genotype of rs2279343 (c.785A > G) prolonged survival (p < 0.05). Furthermore, among liver metastatic patients, AG genotype of rs2279343 (c.785A > G) was associated with a 47% reduced risk of death and a 6-month-longer overall survival (p < 0.05). Among non-liver metastatic patients, hazard ratios of CT/TT genotype of rs8192719 (c.1294 + 53C > T) were 0.45 for progression and 0.40 for death; and the corresponding survival was improved by 6 months and 16 months, respectively (p < 0.05). Genotypes of CYP2B6 had an interaction with clinical efficacy of docetaxel and thiotepa on metastatic breast cancer patients; and metastatic sites also affected clinical responses. Further therapies should take into account of chemotherapy regimen, genotypes of metabolizing enzymes and metastatic sites for the particular subpopulation.

  16. Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

    PubMed Central

    Cairncross, G.; Swinnen, L.; Bayer, R.; Rosenfeld, S.; Salzman, D.; Paleologos, N.; Kaminer, L.; Forsyth, P.; Stewart, D.; Peterson, K.; Hu, W.; Macdonald, D.; Ramsay, D.; Smith, A.

    2000-01-01

    The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status. PMID:11303620

  17. Neurologic complications of chemotherapy and other newer and experimental approaches.

    PubMed

    Soffietti, Riccardo; Trevisan, Elisa; Rudà, Roberta

    2014-01-01

    Neurologic complications of conventional cytototxic agents as well as those from monoclonal antibodies and targeted therapies are increasingly observed in patients with cancer. The major categories are represented by alkylating agents (platinum compounds, ifosfamide, procarbazine, thiotepa), mitotic spindle inhibitors (vinca alkaloids, taxanes, etoposide, teniposide), proteasome inhibitors (bortezomib), antibiotics, antimetabolites, thalidomide, lenalidomide, topoisomerase inhibitors, interferon-α, hormones, bevacizumab, trastuzumab, and small tyrosine kinase inhibitors. Peripheral neuropathy is a common adverse effect of a number of chemotherapeutic drugs and often represents a critical factor limiting an adequate dose-intensity of chemotherapy. Regarding the central nervous system (CNS), it is vulnerable to many forms of toxicity from chemotherapeutic agents, including encephalopathy syndromes and confusional states, seizures, headache, cerebrovascular complications, visual loss, cerebellar syndromes, and myelopathy. For a given drug, the occurrence of CNS toxicity depends on several factors, including the total dose, route of administration, presence of structural brain lesions, exposure to prior or concurrent irradiation, and interactions with other drugs. However, many of the neurotoxic reactions are rare and idiosyncratic, and remain unpredictable. Several forms of neuroprotection and rehabilitation are being investigated. Last, the so-called "chemobrain" is an emerging issue, as it is a model of a subtle of and long-lasting damage to neuronal structures from some antineoplastic agents. © 2014 Elsevier B.V. All rights reserved.

  18. Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer.

    PubMed

    de Almeida, Carlos E B; Alves, Lais Nascimento; Rocha, Henrique F; Cabral-Neto, Januário Bispo; Missailidis, Sotiris

    2017-06-20

    Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects. Thus, chemotherapy or radiotherapy agents, famous for their side effects, can be coupled to aptamers for specific delivery. Equally, siRNA have great therapeutic potential and specificity, but one of their shortcomings remain the delivery and internalisation into cells. Various methodologies have been proposed to date, including aptamers, to resolve this problem. Therapeutic or imaging reagents benefit from the adaptability and ease of chemical manipulation of aptamers, their high affinity for the specific marker of a cell type, and their internalisation ability via cell mediated endocytosis. In this review paper, we explore the potential of the aptamers as delivery agents and offer an update on current status and latest advancements. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine

    PubMed Central

    Segura-Pacheco, Blanca; Perez-Cardenas, Enrique; Taja-Chayeb, Lucia; Chavez-Blanco, Alma; Revilla-Vazquez, Alma; Benitez-Bribiesca, Luis; Duenas-González, Alfonso

    2006-01-01

    Background The development of resistance to cytotoxic chemotherapy continues to be a major obstacle for successful anticancer therapy. It has been shown that cells exposed to toxic concentrations of commonly used cancer chemotherapy agents develop DNA hypermetylation. Hence, demethylating agents could play a role in overcoming drug resistance. Methods MCF-7 cells were rendered adriamycin-resistant by weekly treatment with adriamycin. Wild-type and the resulting MCF-7/Adr cells were analyzed for global DNA methylation. DNA methyltransferase activity and DNA methyltransferase (dnmt) gene expression were also determined. MCF-7/Adr cells were then subjected to antisense targeting of dnmt1, -3a, and -b genes and to treatment with the DNA methylation inhibitor hydralazine to investigate whether DNA demethylation restores sensitivity to adriamycin. Results MCF-7/Adr cells exhibited the multi-drug resistant phenotype as demonstrated by adriamycin resistance, mdr1 gene over-expression, decreased intracellular accumulation of adriamycin, and cross-resistance to paclitaxel. The mdr phenotype was accompanied by global DNA hypermetylation, over-expression of dnmt genes, and increased DNA methyltransferase activity as compared with wild-type MCF-7 cells. DNA demethylation through antisense targeting of dnmts or hydralazine restored adriamycin sensitivity of MCF-7/Adr cells to a greater extent than verapamil, a known inhibitor of mdr protein, suggesting that DNA demethylation interferes with the epigenetic reprogramming that participates in the drug-resistant phenotype. Conclusion We provide evidence that DNA hypermethylation is at least partly responsible for development of the multidrug-resistant phenotype in the MCF-7/Adr model and that hydralazine, a known DNA demethylating agent, can revert the resistant phenotype. PMID:16893460

  20. Comparison of single agent versus combined chemotherapy in previously treated patients with advanced urothelial carcinoma: a meta-analysis.

    PubMed

    Wu, Xiao-Jun; Zhi, Yi; He, Peng; Zhou, Xiao-Zhou; Zheng, Ji; Chen, Zhi-Wen; Zhou, Zhan-Song

    2016-01-01

    Platinum-based chemotherapy is the standard treatment for advanced urothelial cancer (UC) and is generally used in the first-line setting. However, the optimal salvage treatment for previously treated UC patients is unclear. We conducted a systematic review of published clinical trials of single agent versus combined chemotherapy as salvage treatment in previously treated UC patients. Trials published between 1994 and 2015 were identified by an electronic search of public databases (MEDLINE, EMBASE, Cochrane library). All relevant studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), disease control rate (DCR), median progression-free and overall survival (PFS, OS), and grade 3/4 toxicities were extracted and analyzed using Comprehensive Meta Analysis software (Version 2.0). Fifty cohorts with 1,685 patients were included for analysis: 814 patients were treated with single agent chemotherapy and 871 with combined chemotherapy. Pooled OS was significantly higher at 1 year for combined chemotherapy than for single agent (relative risk [RR] 1.52; 95% CI: 1.01-2.37; P=0.03) but not for 2-year OS (RR 1.31; 95% CI: 0.92-1.85; P=0.064). Additionally, combined chemotherapy significantly improved ORR (RR 2.25; 95% CI: 1.60-3.18; P<0.001) and DCR (RR 1.12; 95% CI: 1.01-1.25, P=0.033) compared to single agent for advanced UC patients. As for grade 3 and 4 toxicities, more frequencies of leukopenia and thrombocytopenia were observed in the combined chemotherapy than in single agent group, while equivalent frequencies of anemia, nausea, vomiting, and diarrhea were found between the two groups. In comparison with single agent alone, combined chemotherapy as salvage treatment for advanced UC patients significantly improved ORR, DCR, and 1-year OS, but not 2-year OS. Our findings support the need to compare combined chemotherapy with single agent alone in the salvage setting in large prospective

  1. Multi-agent chemotherapy for mast cell tumours in the dog.

    PubMed

    Gerritsen, R J; Teske, E; Kraus, J S; Rutteman, G R

    1998-01-01

    Seventeen dogs with mast cell tumours received chemotherapy. Fifteen dogs were treated with a vincristine, cyclophosphamide, hydroxyurea, and prednisolone (VCHP) regimen. Seven of these were later switched to doxyrubicin and prednisolone either because they stopped responding or because they did not respond from the start of the treatment. Two dogs received the latter regimen as the primary therapy. All dogs were treated with cimitidine and metoclopramide to minimize the effect of paraneoplastic syndrome associated with histamine release. Ten of the 17 dogs were found to respond (4/17 complete response (CR), 6/17 partial response (PR)). Response duration varied from 39 to 910 days (median 53 days), including 3 dogs with a CR that lasted more than 2 years. Survival time in responders varied from 41 to 910 days (median 97 days) and from 30 to 126 (median 39) in the other 7 dogs. Dogs that became refractory to VCHP did not respond to doxyrubicin and prednisolone. It is concluded that multi-agent chemotherapy has anti-tumour activity in a considerable proportion of dogs with mast cell tumours, but its efficacy is variable. The multivariate analyses showed that significant factors predicting survival in dogs with mast cell tumours were sex (P = 0.009), absence or presence of non-abdominal distant metastases, or abdominal metastases, respectively (P = 0.023), and malignancy grade of the tumours (P = 0.053).

  2. [Sensitivity of esophageal cancer to anticancer agents and supplementary chemotherapy combined with surgical treatment].

    PubMed

    Masaki, Y; Ishigami, K; Oka, M; Matsumoto, N; Honma, K; Uchiyama, T

    1986-04-01

    The authors examined the sensitivities of esophageal cancer to Bleomycin (BLM), Peplomycin (PEP), Cisplatin (CDDP) and 5-FU by the INAS method using 3H-thymidine or 14C-formate as labeled precursors, and determined the concentrations of anticancer agents in cancer lesions by the Band Culture method. On the other hand, the authors investigated the superiority or inferiority of various methods of BLM administration by observing the prevention effect of BLM on the development of experimental esophageal cancer in rats. Forty-three cases out of 76, 57%, showed a sensitivity to BLM, 60% to PEP, 38% to CDDP and 56% to 5-FU. As to the types of roentgenological findings, the superficial and tumorous types showed a high sensitivity rate. As to the types of macroscopical findings, the protruded and superficial types showed a high sensitivity rate. As to the types of histological findings, well differentiated squamous cell carcinoma showed a high sensitivity rate. Sensitivity was higher in metastatic lymph nodes than in main cancer lesions. Tumor tissues which had undergone previous hyperthermic management (at 42 degrees C) showed a higher sensitivity than those which had not. PEP at a half dose brought about the same grade of anticancer effect as BLM. The sensitivities of esophageal cancer to various anticancer agents showed individual differences among clinical cases. Therefore, combination chemotherapy for esophageal cancer was thought to be an effective administration method. The divided administration of small doses of BLM was thought to be more superior than the one-shot administration of a large dose for esophageal cancer. The results of the INAS sensitivity test were perfectly coincident with the effects of chemotherapy in clinical cases of esophageal cancer.

  3. The Use of Triethylenethiophosphoramide (Thio-TEPA) in the Treatment of Metastatic Carcinoma of the Breast

    PubMed Central

    Kuwayti, Kamal; Hilton, James H. B.

    1963-01-01

    Twenty-two patients with metastatic breast cancer were treated by a combination of testosterone and N,N′,N″, triethylenethiophosphoramide (Thio-TEPA). All had undergone mastectomy and received radiation; six had had an oophorectomy and 12 had had oophorectomy and adrenalectomy. For its marrow-stimulating effect testosterone was given intramuscularly, 100 mg. daily for five days; then 100 mg. of depo-testosterone was given intramuscularly once a week. On the sixth day of treatment, 15 mg. of Thio-TEPA was given intramuscularly and repeated daily or every second day until a definite depression of the leukocyte and/or platelet counts occurred. To 15 patients a total dose of 200 mg. or more of triethylenethiophosphoramide was given. Thirteen patients improved subjectively and five of these improved objectively. The duration of improvement varied between one and 12 months. Treatment was most effective in patients with bony metastases. PMID:13927682

  4. Liquid chromatography-thermospray mass spectrometry of DNA adducts formed with mitomycin C, porfiromycin and thiotepa.

    PubMed

    Musser, S M; Pan, S S; Callery, P S

    1989-07-14

    High-performance liquid chromatography (HPLC) and thermospray mass spectrometry were combined for the analysis of DNA adducts formed from the interaction of the anticancer drugs mitomycin C, porfiromycin and thiotepa with calf thymus DNA. The adducts formed from reaction of mitomycin C and porfiromycin with DNA were separated from unmodified nucleosides by HPLC on a C18 column and identified by thermospray mass spectrometry. Thiotepa DNA adducts readily depurinated from DNA and were chromatographed and identified by thermospray liquid chromatography-mass spectrometry as the modified bases without the ribose moiety attached. The utility of thermospray mass spectrometry for the identification of microgram quantities of nucleoside adducts and depurinated base adducts of these anticancer drugs was demonstrated.

  5. Two novel high-dose treatment regimens for metastatic breast cancer--ifosfamide, carboplatin, plus etoposide and mitoxantrone plus thiotepa: outcomes and toxicities.

    PubMed

    Fields, K K; Elfenbein, G J; Perkins, J B; Hiemenz, J W; Janssen, W E; Zorsky, P E; Ballester, O F; Kronish, L E; Foody, M C

    1993-10-01

    This report describes the results of two phase I/II dose escalation trials for the treatment of metastatic breast cancer. Successive groups of patients with metastatic breast cancer responsive to induction therapy following standard doses of chemotherapy were treated with escalating doses of ifosfamide (6,000 to 24,000 mg/m2), carboplatin (1,200 to 2,100 mg/m2), and etoposide (1,800 to 3,000 mg/m2) followed by autologous stem cell rescue. The maximum tolerated doses of these drugs were defined as ifosfamide 20,100 mg/m2, carboplatin 1,800 mg/m2, and etoposide 3,000 mg/m2. Major nonhematologic toxicity consisted of mucositis and enteritis, and the dose-limiting toxicities were central nervous system toxicity and acute renal failure. The overall treatment-related mortality rate was 4%. The event-free survival rate at 500 days for these patients was 31%. Patients with metastatic breast cancer refractory to all standard dose therapy were treated with escalating doses of mitoxantrone (45 to 105 mg/m2) and thiotepa (900 to 1,350 mg/m2) followed by autologous stem cell rescue. The maximum tolerated doses of these drugs were defined as mitoxantrone 90 mg/m2 and thiotepa 1,200 mg/m2 with mucositis and enteritis as the major nonhematologic toxicities and delayed myelosuppression as the dose-limiting toxicity. Twelve percent of the patients remain event free at 500 days and the treatment-related mortality rate for this group of heavily pretreated patients was 17%. These data suggest that patients with metastatic breast cancer may benefit from high-dose therapy and that treatment-related toxicity is tolerable.

  6. Release of thiotepa sterilized males into caged populations of Aedes aegypti: life table analysis.

    PubMed

    Gato, René; Companioni, Ariamys; Bruzón, Rosa Y; Menéndez, Zulema; González, Aileen; Rodríguez, Misladys

    2014-04-01

    Successful SIT trials against mosquitoes in the 1960-70s were achieved by sterilizing male mosquitoes using chemosterilants. Their use was discontinued after concerns were raised about the effect of residues on non-target organisms, although scant evidence has been published. Irradiation is an expensive process; chemosterilization could be an affordable option for implementing SIT programs in developing countries. We compare life table parameters of three Aedes aegypti populations comprising different ratios of thiotepa-treated and non-treated males in order to identify the impact on reproductive potential of the presence of sterile males. No difference was observed in the survival of the treated and untreated males. The release of thiotepa sterilized males into caged Ae. aegypti populations had no effect on death or survival probability of the individuals in the cages but the fecundity of females was significantly reduced, as evaluated by hatch rate and stable age structure parameters. The significant decreases in net reproduction rate, finite rate of natural increase and intrinsic rate of natural increase in populations including sterile males are sufficient to indicate that such populations would not be able to proliferate in natural conditions. This suggests that release of Ae. aegypti thiotepa-treated males could be effective in reducing the reproductive capability of the target population and consequently contribute to vector control.

  7. Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain - The Cause of "Chemo Brain"

    DTIC Science & Technology

    2005-11-01

    of Neuronal Birthing in the Brain – The Cause of “Chemo Brain” PRINCIPAL INVESTIGATOR: Robert A. Gross, M.D., Ph.D. CONTRACTING...AND SUBTITLE 5a. CONTRACT NUMBER Chemotherapy Agents and the Inhibition of Neuronal Birthing in the Brain – The Cause of “Chemo Brain” 5b. GRANT...with respect to their ability to impair the birthing of new neurons in the hippocampus of adult mice. By testing whether chemotherapeutic agents

  8. The use of antimicrobial agents in children with fever during chemotherapy-induced neutropenia: the importance of risk stratification.

    PubMed

    Palazzi, Debra L

    2011-10-01

    Children with fever and chemotherapy-induced or cancer-associated neutropenia should be assessed with complete history and physical examinations, undergo appropriate diagnostic studies, and promptly receive broad-spectrum empirical antimicrobial therapy. Assessment of risk for severe infection is crucial in determining the appropriate antimicrobial, route, venue, and duration of empirical antimicrobial therapy and need for prophylactic antimicrobial agents.

  9. Assessment of the novel tubulin-binding agent EHT 6706 in combination with ionizing radiation or chemotherapy.

    PubMed

    Clémenson, Céline; Chargari, Cyrus; Désiré, Laurent; Casagrande, Anne-Sophie; Bourhis, Jean; Deutsch, Eric

    2012-12-01

    The potential of EHT 6706, a novel tubulin-binding agent, was investigated in combination with ionizing radiation (IR) and with conventional cytotoxic chemotherapy agents. Cell proliferation, cell cycle, apoptosis and clonogenic assays were performed in five human cancer cell lines: H460 (non small cell lung carcinoma, NSCLC), HCT116 and HCT116 p53-/- (colorectal cancer), MDA-MB-231 (breast cancer), and MiaPaca2 cells (pancreatic cancer). The drug inhibited cell proliferation in all cell lines. This effect was associated with G2/M arrest and activation of apoptosis in a dose-dependent manner. The drug was then tested in combination with chemotherapy and IR in vitro. Effects on proliferation and clonogenic survival were analyzed. EHT 6706 treatment inhibited clonogenic survival synergistically with IR in H460 and MiaPaca2 cell lines. In the remaining cell lines, the effects of EHT 6706 and IR were additive. For H460 and MiaPaca2 cell lines, the highest effect was seen when cells were exposed for 20 h to EHT 6706 before being irradiated. EHT 6706 also exerted additive inhibition of proliferation when given in combination with conventional chemotherapy agents, such as oxaliplatin, cisplatin and gemcitabine in H460 and MiaPaca2 tumor cell lines. These data show that EHT 6706 could act synergistically with IR and additively with chemotherapy in tumor cell lines in vitro. This provides a good rationale to further assess EHT 6706 in combination protocols and confirm these effects in vivo.

  10. Clinically relevant doses of chemotherapy agents reversibly block formation of glioblastoma neurospheres

    PubMed Central

    Mihaliak, Alicia M.; Gilbert, Candace A.; Li, Li; Daou, Marie-Claire; Moser, Richard P.; Reeves, Andrew; Cochran, Brent H.; Ross, Alonzo H.

    2010-01-01

    Glioblastoma patients have a poor prognosis, even after surgery, radiotherapy, and chemotherapy with temozolomide or 1,3-bis(2-chloroethy)-1-nitrosourea. We developed an in vitro recovery model using neurosphere cultures to analyze the efficacy of chemotherapy treatments, and tested whether glioblastoma neurosphere initiating cells are resistant. Concentrations of chemotherapy drugs that inhibit neurosphere formation are similar to clinically relevant doses. Some lines underwent a transient cell cycle arrest and a robust recovery of neurosphere formation. These results indicate that glioblastoma neurospheres can regrow after treatment with chemotherapy drugs. This neurosphere recovery assay will facilitate studies of chemo-resistant subpopulations and methods to enhance glioblastoma therapy. PMID:20435409

  11. Hyperfractionated radiotherapy and multi-agent chemotherapy (procarbazine, ACNU and vincristine) for high-grade gliomas: a prospective study.

    PubMed

    Ogawa, Kazuhiko; Yoshii, Yoshihiko; Toita, Takafumi; Saito, Atsushi; Kakinohana, Yasumasa; Iraha, Shiro; Sugimoto, Koichi; Tsuchida, Yukihiro; Tamaki, Wakana; Adachi, Genki; Hyodo, Akio; Murayama, Sadayuki

    2006-01-01

    To evaluate the feasibility, efficacy and toxicity of hyperfractionated radiotherapy and multi-agent chemotherapy, including procarbazine, nimustine (ACNU) and vincristine, in adults with high-grade gliomas. Radiotherapy was administered using two fractions per day of 1.2 Gy to a total dose of 72 Gy. The chemotherapy consisted of procarbazine (90 mg/m2 orally, days 1 to 14), ACNU (80 mg/m2 intravenously, day 1) and vincristine (0.5 mg/m2 intravenously, days 1 and 8) and was administered during and after radiotherapy, up to a maximum of four courses. From September 1997 to August 1999, a total of ten patients (five with glioblastoma and five with grade 3 gliomas) were enrolled. All ten patients were able to complete a total dose of 72 Gy hyperfractionated radiotherapy with one course of concurrent chemotherapy. Of eight assessable patients, three (38%) had an objective response, comprising two CR and one PR. The median time to progression was 10.7 months and the median survival time of all patients was 15.0 months. Although grade 4 leukopenia and grade 4 thrombocytopenia occurred in 10% and 10% of all patients, respectively, these were transient and no patients developed neutropenic fever or intracranial hemorrhage. No serious non-hematological or late toxicities occurred. Hyperfractionated radiotherapy and multi-agent chemotherapy using procarbazine, ACNU and vincristine is safe and well tolerated for high-grade gliomas.

  12. A systematic review of limited sampling strategies for platinum agents used in cancer chemotherapy.

    PubMed

    Loh, Gabriel W; Ting, Lillian S L; Ensom, Mary H H

    2007-01-01

    Despite evidence in the literature suggesting that a strong correlation exists between the pharmacokinetic parameters and pharmacodynamic effect of anticancer agents, many of these agents are still dosed by body surface area. Therapeutic drug monitoring with the aim of pharmacokinetic-guided dosing would not only maintain target concentrations associated with efficacy but may potentially minimise the likelihood of dose-related systemic toxicities. The pharmacokinetic parameter that displays the best correlation with the pharmacodynamics of anticancer drugs is the area under the plasma concentration-time curve (AUC). However, accurate determination of the AUC requires numerous blood samples over an extended interval, which is not feasible in clinical practice. Therefore, limited sampling strategies (LSSs) have been proposed as a means to accurately and precisely estimate pharmacokinetic parameters with a minimal number of blood samples. LSSs have been developed for many drugs, particularly ciclosporin and other immunosuppressants, as well as for certain anticancer drugs. This systematic review evaluates LSSs developed for the platinum compounds and categorises 18 pertinent citations according to criteria adapted from the US Preventive Services Task Force. Thirteen citations (four level I, six level II-1, three level II-2) pertained to LSSs for carboplatin, four citations (one level II-1, one level II-2, two level III) to cisplatin LSSs, and one citation (level II-2) to nedaplatin. Based on the current evidence, it appears that LSSs may be useful for pharmacokinetic-guided dosage adjustments of carboplatin in both adults and children with cancer. Although some validation studies suggest that LSSs can be extended to different cancer populations or different chemotherapy regimens, other studies dispute this finding. Although the use of LSSs to predict the pharmacokinetic parameters of cisplatin and nedaplatin appear promising, the quality of evidence from published

  13. Medication Therapy Management for Patients Receiving Oral Chemotherapy Agents at a Community Oncology Center: A Pilot Study.

    PubMed

    Bertsch, Nathan S; Bindler, Ross J; Wilson, Poppy L; Kim, Anne P; Ward, Beverly

    2016-10-01

    Purpose: To determine the impact of a pharmacist-driven medication therapy management (MTM) program for patients receiving oral chemotherapy agents. Methods: We assessed the impact of MTM consultations with a pharmacist for patients who were receiving a new prescription for an oral chemotherapy agent. Data were assessed for outcomes including (1) number of medication errors identified in electronic medical records (EMRs), (2) number of interventions performed by the pharmacist, (3) time spent on the MTM process, and (4) patient satisfaction. Data were compared between patients who received their oral chemotherapy agents from the onsite specialty pharmacy or from a mail-order pharmacy. The data were also examined for correlations, and logistic regression was utilized to determine the largest variant cofactor to create an equation for estimating the number of errors in a patient's EMR. Results: Fifteen patients received an MTM consultation, and the pharmacists identified an average of 6 medication EMR errors per patient. There was an average of 3 pharmacist-led interventions per patient. Multiple significant correlations were noted between the variables: (1) total number of prescriptions a patient was taking, (2) total number of medication errors identified, (3) time spent on the MTM process, and (4) total number of interventions performed by the pharmacist. Patient satisfaction was favorable for the program. Conclusion: The implementation of a pharmacist-driven MTM program for patients receiving a prescription for an oral chemotherapy agent had a significant impact on patient care by improving medication reconciliation, identifying drug-related problems, and strengthening pharmacist-patient interactions in the oncology clinic.

  14. Role of chemotherapy and molecularly targeted agents in the treatment of adenoid cystic carcinoma of the lacrimal gland.

    PubMed

    Le Tourneau, Christophe; Razak, Albiruni R A; Levy, Christine; Calugaru, Valentin; Galatoire, Olivier; Dendale, Rémi; Desjardins, Laurence; Gan, Hui K

    2011-11-01

    Adenoid cystic carcinoma (ACC) is the most common malignant epithelial cancer of the lacrimal gland. Despite a slow rate of growth, ACCs are ultimately associated with poor clinical outcome. Given the rarity of this disease, most recommendations regarding therapy are guided by expert opinion and retrospective data rather than level 1 evidence. Surgery and postoperative radiation therapy are commonly used as initial local treatment. In patients at high risk of recurrence, concomitant platinum-based chemotherapy may be added to postoperative radiotherapy in an attempt to enhance radio-sensitivity. While encouraging responses have been reported with intra-arterial neoadjuvant chemotherapy, this strategy is associated with substantial toxicity and should be considered investigational. For patients with metastatic disease not amenable to surgery or radiotherapy, chemotherapy may have a role based on its modest efficacy in non-lacrimal ACC. Similarly, molecular targeted agents may have a role, although the agents tested to date in non-lacrimal ACC have been disappointing. A better understanding of the biology of ACC will be crucial to the future success of developing targeted agents for this disease.

  15. Monascus Pigment Rubropunctatin: A Potential Dual Agent for Cancer Chemotherapy and Phototherapy.

    PubMed

    Zheng, Yunquan; Zhang, Yun; Chen, Deshan; Chen, Haijun; Lin, Ling; Zheng, Chengzhuo; Guo, Yanghao

    2016-03-30

    The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR), and its cytotoxic activities against human cervical carcinoma HeLa cells were studied under the conditions with or without light irradiation. The IC50 value of rubropunctatin against HeLa cells in the dark was 93.71 ± 1.96 μM (24 h), while the cytotoxic activity was enhanced more than 3 times (IC50 = 24.02 ± 2.17 μM) under light irradiation (halogen lamp, 500 W; wavelength, 597-622 nm; and fluence rate, 15 mW cm(-2), for 30 min). However, the IC50 value of rubropunctatin against the immortalized human cervical epithelial H8 cells was more than 300 μM, even under light irradiation, indicating that rubropunctatin has a favorable selectivity index (SI). Treatment of HeLa cells with rubropunctatin in the dark or under light irradiation resulted in a dose-dependent apoptosis, as validated by the increase in the percentage of cells in the sub-G1 phase and phosphatidylserine externalization, and the inductive effect on HeLa cell apoptosis was boosted by the light irradiation. In addition, treatment with rubropunctatin alone or under light irradiation was found to induce apoptosis in HeLa cells via the mitochondrial pathway, including loss of mitochondrial membrane potential, activation of caspase-3, caspase-8, and caspase-9, and increase of the level of intracellular reactive oxygen species (ROS). It was suggested that rubropunctatin could be a promising natural dual anticancer agent for photodynamic therapy and chemotherapy.

  16. Pharmacotherapeutic Management of Metastatic, Castration-Resistant Prostate Cancer in the Elderly: Focus on Non-Chemotherapy Agents

    PubMed Central

    Beer, Tomasz M.

    2015-01-01

    In the past 4 years, five new agents have been approved for metastatic, castration-resistant prostate cancer. Four of them are non-chemotherapeutic and generally well tolerated. However, each has toxicities that can negatively impact patients, particularly the elderly. This review covers the epidemiology of prostate cancer in elderly men. It discusses the efficacy data for sipuleucel-T, abiraterone in chemotherapy-naïve patients, enzalutamide in chemotherapy-naïve patients and radium-223 and presents any additional studies done for those over 75 years of age. Disease burden, such as the presence or absence of visceral disease, and comorbid conditions weigh into the selection of therapy and are discussed here. Drug–drug interactions between these agents and other drugs commonly used in the elderly population are also considered. The emerging therapies tasquinimod and ipilimumab are reviewed. With the arrival of so many agents for prostate cancer, selection of the most appropriate agent can be perplexing, particularly because these agents were tested against placebo, not one another. Furthermore, the study population differs significantly from those seen in clinical practice. This review addresses these issues. PMID:25387443

  17. Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

    PubMed

    Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

    2016-01-01

    Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

  18. The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation

    SciTech Connect

    Hoppe, R.T.; Kushlan, P.; Kaplan, H.S.; Rosenberg, S.A.; Brown, B.W.

    1981-09-01

    Between 1975 and 1978, 51 patients with favorable histology non-Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed.

  19. Characterization of nonexchangeable radioactivity in L1210 cells incubated with ( sup 14 C)thiotepa: Labeling of phosphatidylethanolamine

    SciTech Connect

    Egorin, M.J.; Snyder, S.W. )

    1990-07-01

    N,N',N''-Triethylenethiophosphoramide ((14C)thiotepa) accumulation by L1210 cells is a biphasic process. A very rapid initial phase is followed by a much slower second phase that reflects accumulation of radioactivity in a form that is not lost or exchanged when cells are resuspended and incubated in drug-free medium for up to 8 h. In this study we attempted to characterize this nonexchangeable radioactivity. Nuclei (10(7)) isolated from L1210 cells and incubated with (14C)thiotepa did not accumulate 14C during incubations of up to 5 h. Similarly, nuclei isolated from 10(7) L1210 cells that had been shown to accumulate nonexchangeable 14C after incubation with (14C)thiotepa did not show an increase in nuclear-associated 14C. Eighty to 85% of nonexchangeable 14C in L1210 cells incubated with (14C)thiotepa was soluble in ethanol or chloroform:methanol (2:1, v/v), and although most of this cell-associated nonexchangeable 14C was precipitated by trichloroacetic acid, subsequent treatment of that precipitate with methanol solubilized most of the 14C so that only 15 to 20% remained with the final precipitate. When chloroform:methanol-soluble nonexchangeable 14C was analyzed with thin-layer chromatography systems suitable for thiotepa or simple lipids, all radioactivity remained at the origin. In contrast, when analyzed with one- and two-dimensional thin-layer chromatographic systems suitable for complex lipids, all chloroform:methanol-soluble radioactivity was associated with a single lipid spot. This lipid cochromatographed with phosphatidylethanolamine, reacted with ninhydrin but not with 4-(p-nitrobenzyl)pyridine or the Dragendorff choline reagent, and was digested by phospholipases C and D, all of which lead to its identification as phosphatidylethanolamine.

  20. Improving adherence with oral antiemetic agents in patients with breast cancer receiving chemotherapy.

    PubMed

    Hendricks, Carolyn B

    2015-05-01

    In this small breast cancer-dedicated solo practice, a retrospective medical record review disclosed the following: significant rate of chemotherapy-related nausea and vomiting and discordance between patient-reported compliance with prescribed antiemetics and medical record documentation of compliance. As part of the curriculum for the American Society of Clinical Oncology (ASCO) Quality Training Program, a quality improvement project was developed to improve adherence to oral antiemetics in our patients with breast cancer receiving highly emetogenic chemotherapy. The following steps were undertaken in plan-do-study-act cycles to improve adherence: enhanced patient education at time of chemotherapy consent, implementation of standardized in-person or e-mail contact with our patients receiving chemotherapy, and improvement of our electronic health record documentation of adherence to oral antiemetics. A run chart was generated to analyze our data. After our interventions, the percentage of patients who took their antiemetics as prescribed rose from a baseline of 49% to 79%. Significant improvement in adherence to oral antiemetics among patients with breast cancer receiving chemotherapy was achieved and sustained in this small-practice setting using the framework provided by participation in the ASCO Quality Training Program. Copyright © 2015 by American Society of Clinical Oncology.

  1. 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

  2. [Effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy and research the drug resistance].

    PubMed

    Lu, Li-Xia; Wang, Ying; Lu, Xiao-Jun; Li, Da-Jiang; Xu, Kong-Wen; Tang, Hong; Liu, Li; Liu, Cong; Wang, Li-Chun

    2011-09-01

    To study the effect of Lamivudine on chronic hepatitis B patients with chemotherapy or immunosuppressive agents therapy, and research the drug resistance. Thirty-one cases of chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents therapy were enrolled and divided into two group, HBeAg-positive group (n = 20) and HBeAg-negative group (n = 11), then given Lamivudine for preventive treatment. Virus response, biochemical response and serum response were evaluated as effective index, and analyzed the difference between the two groups for statistical significance. Meanwhile, drug resistance rate, impact factor of resistance and security were analyzed. At the end of 48 weeks' treatment, the rate of HBV DNA under the detection limit was 41.94%, and the decline of HBV DNA compared with baseline was 2.35 lg. The normalization rate of ALT, the negative rate of HbeAg and the seroconversion rate of HBeAg/HBeAb were 92.31%, 25% and 20% respectively. HBeAg-positive group and HBeAg-negative group patients in the complete virus response, the decline of HBV DNA compared with baseline and the resistance rate had no statistics significance (P > 0.05). At the same time, virology breakthrough occurred in four patients, and resistance mutation was detected in three cases among them. The resistance rate was 9.68%. The type of genotype mutation were all rtM204I. Multi-factor regression analysis showed that the baseline factors including age, gender, HBeAg status, baseline HBV DNA level and baseline ALT had no significant compact on drug resistance. Serious adverse reactions were not found in all patients. For chronic hepatitis B patients who needed chemotherapy or immunosuppressive agents treatment, Lamivudine for preventive antiviral therapy is a good option with good antiviral effect and safety. It is necessary to pay attention to the occurrence of drug resistance.

  3. Thiotepa Injection

    MedlinePlus

    ... that begins in the female reproductive organs where eggs are formed), breast, and bladder cancer. It is ... comes as a powder to be mixed with liquid to be injected intravenously (into a vein) by ...

  4. Budget impact analysis on erythropoiesis–stimulating agents use for the management of chemotherapy-induced anaemia in Greece

    PubMed Central

    2013-01-01

    Background Chemotherapy-induced anaemia is a common and significant complication of chemotherapy treatment. Blood transfusion and administration of Erythropoiesis-Stimulating Agents (ESAs) either alone or in combination with iron are the most widely used therapeutic options. In Greece, ESAs are among the top ten therapeutic groups with the highest pharmaceutical expenditure, since they are fully reimbursed by social security funds. The objective of the study is to determine potential cost savings related with the use of biosimilar over originator ESAs for the management of the newly diagnosed chemotherapy-induced anemic patients. Methods A budget impact analysis has been carried through the elaboration of national epidemiological, clinical and economic data. Epidemiological data derived from WHO (GLOBOCAN) and the European Cancer Anaemia Survey. Clinical data reflect oncology patients’ disease management. ESAs consumption was based on data from the biggest social security fund (IKA). The administration of ESAs under different dosing schemes and time periods has been estimated by separating them in originators and biosimilars as well as by classifying anaemic patients in responders and non-responders. Cost analysis is based on newly diagnosed patients’ alternative treatment scenarios. Treatment costs and prices are used in 2012 values. The Social Security Funds’s perspective was undertaken. Results Based on the annual incidence rates, 2.551 newly diagnosed chemotherapy-induced anemic patients are expected to be treated with ESAs. Average cost of treatment on originators ESAs for responders is €2.887 for the 15-week ESAs treatment and €5.019 for non-responders, while on biosimilars €2.623 and €4.009 respectively. Treatment cost on biosimilars is 10.1% lower than originators for responders and 25.2% for non-responders. Budget impact estimates show that treating anemic patients with originator ESAs was estimated at €10.084.800 compared to €8

  5. The High Incidence of Vascular Thromboembolic Events in Advanced Urothelial Cancer Treated with Platinum Chemotherapy Agents

    PubMed Central

    Tully, Christopher M.; Apolo, Andrea B.; Zabor, Emily C.; Regazzi, Ashley M.; Ostrovnaya, Irina; Rosenberg, Jonathan E.; Bajorin, Dean F.

    2016-01-01

    Background This study compared the incidence of vascular thromboembolic events (VTEs) in advanced urothelial carcinoma (UC) patients treated with either gemcitabine/carboplatin (GCb), gemcitabine/carboplatin/bevacizumab (GCbBev) or gemcitabine/cisplatin (GCis). Patients and Methods Patients with advanced UC treated with GCbBev on protocol were analyzed prospectively and two contemporary control cohorts receiving GCb or GCis were obtained retrospectively. VTE was defined as either venous or arterial (myocardial infarctions or cerebral vascular accidents) thrombosis. VTEs were treatment-related if they occurred between the start of treatment and 4 weeks after completion of chemotherapy. Associations with chemotherapy regimen were tested using either the Fisher’s exact test or Kruskal-Wallis test. Clinical factors associated with VTEs were analyzed using conditional logistic regression stratified by treatment regimen. Results Among 198 patients, VTEs occurred in 13/51 (26%) GCbBev patients, 22/92 (24%) GCb patients and 8/55 (15%) GCis patients. Patient characteristics were significantly different between treatment cohorts in terms of age, prior cystectomy, tumor near pelvic vessels, Khorana risk group and anti-platelet therapy. The type of chemotherapy was not associated with any VTEs or type of VTEs (arterial vs. venous). Prior cystectomy was associated with increased risk of VTEs (OR 2.2, 95% CI 1.0–4.9, p=0.047). Conclusions This is the largest series reporting VTEs in UC patients treated with first–line combination platinum-based therapy. The incidence of VTE in cisplatin-treated patients is similar to prior reports. However, the VTE rate in carboplatin-treated patients had not been previously defined and thus represents a new baseline. The addition of bevacizumab does not appear to increase VTE risk. This high incidence of carboplatin-related VTEs warrants further study. PMID:26618338

  6. Large indoor cage study of the suppression of stable Aedes aegypti populations by the release of thiotepa-sterilised males

    PubMed Central

    Gato, René; Lees, Rosemary Susan; Bruzon, Rosa Y; Companioni, Ariamys; Menendez, Zulema; González, Aileen; Rodríguez, Misladys

    2014-01-01

    The sterile insect technique (SIT) is a promising pest control method in terms of efficacy and environmental compatibility. In this study, we determined the efficacy of thiotepa-sterilised males in reducing the target Aedes aegypti populations. Treated male pupae were released weekly into large laboratory cages at a constant ratio of either 5:1 or 2:1 sterile-to-fertile males. A two-to-one release ratio reduced the hatch rate of eggs laid in the cage by approximately a third and reduced the adult catch rate by approximately a quarter, but a 5:1 release drove the population to elimination after 15 weeks of release. These results indicate that thiotepa exposure is an effective means of sterilising Ae. aegypti and males thus treated are able to reduce the reproductive capacity of a stable population under laboratory conditions. Further testing of the method in semi-field enclosures is required to evaluate the mating competitiveness of sterile males when exposed to natural environmental conditions. If proven effective, SIT using thiotepa-sterilised males may be incorporated into an integrated programme of vector control to combat dengue in Cuba. PMID:24863972

  7. Large indoor cage study of the suppression of stable Aedes aegypti populations by the release of thiotepa-sterilised males.

    PubMed

    Gato, René; Lees, Rosemary Susan; Bruzon, Rosa Y; Companioni, Ariamys; Menendez, Zulema; González, Aileen; Rodríguez, Misladys

    2014-06-01

    The sterile insect technique (SIT) is a promising pest control method in terms of efficacy and environmental compatibility. In this study, we determined the efficacy of thiotepa-sterilised males in reducing the target Aedes aegypti populations. Treated male pupae were released weekly into large laboratory cages at a constant ratio of either 5:1 or 2:1 sterile-to-fertile males. A two-to-one release ratio reduced the hatch rate of eggs laid in the cage by approximately a third and reduced the adult catch rate by approximately a quarter, but a 5:1 release drove the population to elimination after 15 weeks of release. These results indicate that thiotepa exposure is an effective means of sterilising Ae. aegypti and males thus treated are able to reduce the reproductive capacity of a stable population under laboratory conditions. Further testing of the method in semi-field enclosures is required to evaluate the mating competitiveness of sterile males when exposed to natural environmental conditions. If proven effective, SIT using thiotepa-sterilised males may be incorporated into an integrated programme of vector control to combat dengue in Cuba.

  8. Outcomes of children with central nervous system germinoma treated with multi-agent chemotherapy followed by reduced radiation.

    PubMed

    Cheng, Sylvia; Kilday, John-Paul; Laperriere, Normand; Janzen, Laura; Drake, James; Bouffet, Eric; Bartels, Ute

    2016-03-01

    CNS germinomas have an excellent prognosis with radiation therapy alone. However, in children, volume and dose of CNS radiation are associated with neurocognitive and neuroendocrine sequelae. Our objective was to determine long-term outcomes of our cohort who received chemotherapy and reduced radiation. This retrospective cohort study analyzed treatment and outcome of intracranial germinoma patients consecutively treated at Sick Kids, Toronto, Canada, from January 2000 to December 2013. 24 children (13 male, 11 female; median age 13.36 years) were identified. Median follow up was 61 months (range 1-144 months). Tumor location was suprasellar (n = 9), bifocal (8), pineal (6), and basal ganglia (1). Three children showed dissemination on imaging. 2/24 had only elevated serum human chorionic gonadotropin, 3/24 only elevated lumbar cerebrospinal fluid (CSF) hCG, and 2/24 had both elevated serum and lumbar CSF hCG. 23/24 children completed treatment and received multi-agent chemotherapy followed by either ventricular radiation (2340-2400 cGy) (n = 9), ventricular radiation + boost (1600 cGy) (n = 8), whole brain (2340 cGy) (n = 3), focal (4000 cGy) (n = 2) or craniospinal radiation (2340 cGy) (n = 1). Five-year progression free and overall survival was 96 and 100 % respectively. 8/24 patients with ventricular radiation ± boost (2340/4000 cGy) displayed stable full scale intelligence quotient over a mean interval of 3 years following radiation, but showed declined processing speed. In this limited experience, excellent 5-year overall survival rates were achieved with chemotherapy followed by reduced whole ventricular radiation even if ventricular radiation was delivered without boost.

  9. Erythropoiesis-stimulating agents (ESAs): do they still have a role in chemotherapy-induced anemia (CIA)?

    PubMed

    Bormanis, Janis; Quirt, Ian; Chang, José; Kouroukis, C Tom; MacDonald, David; Melosky, Barb; Verma, Sunil; Couture, Felix

    2013-08-01

    Anemia in cancer patients can be a result of the underlying cancer or related to treatment. Erythropoiesis-stimulating agents (ESAs) are an important option for many patients with chemotherapy-induced anemia, but are immersed in controversy. This article aims to reconcile conflicting opinions and provide expert guidance for appropriate ESA use. Teleconference, email, and a face-to-face meeting were used to assess ESA therapy "interpretive" data, which included two current meta-analyses, expert guidelines, and regulatory approved indications from Canada, Europe, and the USA. Risks and benefits are associated with both red blood cell transfusions and ESA therapy, including improvements in hemoglobin levels and quality of life. ESAs have been associated with concerns regarding survival and progression of cancer, particularly when used in patients with cancer-related anemia. Although safety concerns do exist, ESA therapy can be considered for use in patients with chemotherapy-induced anemia in accordance with Health Canada labeling. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  10. 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

  11. Multi-agent chemotherapy overcomes glucocorticoid resistance conferred by a BIM deletion polymorphism in pediatric acute lymphoblastic leukemia.

    PubMed

    Soh, Sheila Xinxuan; Lim, Joshua Yew Suang; Huang, John W J; Jiang, Nan; Yeoh, Allen Eng Juh; Ong, S Tiong

    2014-01-01

    A broad range of anti-cancer agents, including glucocorticoids (GCs) and tyrosine kinase inhibitors (TKIs), kill cells by upregulating the pro-apoptotic BCL2 family member, BIM. A common germline deletion in the BIM gene was recently shown to favor the production of non-apoptotic BIM isoforms, and to predict inferior responses in TKI-treated chronic myeloid leukemia (CML) and EGFR-driven lung cancer patients. Given that both in vitro and in vivo GC resistance are predictive of adverse outcomes in acute lymphoblastic leukemia (ALL), we hypothesized that this polymorphism would mediate GC resistance, and serve as a biomarker of poor response in ALL. Accordingly, we used zinc finger nucleases to generate ALL cell lines with the BIM deletion, and confirmed the ability of the deletion to mediate GC resistance in vitro. In contrast to CML and lung cancer, the BIM deletion did not predict for poorer clinical outcome in a retrospective analysis of 411 pediatric ALL patients who were uniformly treated with GCs and chemotherapy. Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate) were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs. Together, our work demonstrates how effective therapy can overcome intrinsic resistance in ALL patients, and suggests the potential of using combinations of drugs that work via divergent mechanisms of cell killing to surmount BIM deletion-mediated drug resistance in other cancers.

  12. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  13. Prevention of chemotherapy-induced ovarian damage: possible roles for hormonal and non-hormonal attenuating agents.

    PubMed

    Roness, Hadassa; Kalich-Philosoph, Lital; Meirow, Dror

    2014-01-01

    demonstrate that co-treatment with these agents will not interfere with the anti-cancer activity of the chemotherapy drugs, or produce genetically comprised embryos. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Chemotherapy for relapsed small cell lung cancer: a systematic review and practice guideline.

    PubMed

    Cheng, Susanna; Evans, William K; Stys-Norman, Denise; Shepherd, Frances A

    2007-04-01

    This clinical practice guideline, based on a systematic review, evaluates chemotherapy options for patients with relapsed small cell lung cancer (SCLC). Relevant randomized trials and meta-analyses were identified through a systematic search of the literature. External feedback was obtained from practitioners in Ontario, and the guideline was approved by the provincial lung cancer disease site group. Six randomized trials met the eligibility criteria and were included for review. One randomized phase III trial of oral topotecan versus no treatment in patients receiving best supportive care found topotecan to have a significant benefit in terms of 6-month survival and quality of life. A randomized phase III trial compared outcomes of carboplatin in patients receiving a combination of etoposide and cisplatin (EP) and found no significant improvement associated with carboplatin, although it was associated with significantly higher grade 3/4 thrombocytopenia. Two randomized trials directly compared chemotherapy regimens (intravenous [i.v.] topotecan versus cyclophosphamide, doxorubicin, and vincristine (CAV); and bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide (BTOC) versus EP), but these trials found no significant differences in terms of disease response or survival. I.v. topotecan was associated with significantly higher toxicities (grade 4 thrombocytopenia and grade 3/4 anemia) and greater improvement in patient-reported symptoms compared with CAV. Two randomized trials of topotecan-treated patients comparing route of administration (i.v. versus oral) found no significant differences in terms of disease response, survival, or quality of life, although oral administration was associated with increased grade 3 or 4 diarrhea in both trials. Evidence on the clinical benefit of second-line therapy in SCLC is limited. Topotecan is the most studied agent in this population; it has a response and survival benefit in comparison with placebo, but it

  15. Fludarabine, Melphalan, Thiotepa and ATG Conditioning for Unrelated Cord Blood Transplantation

    PubMed Central

    Ciurea, Stefan O.; Saliba, Rima M.; Hamerschlak, Nelson; Aurueta, Amado J. Karduss; Bassett, Roland; Fernandez-Vina, Marcelo; Petropoulos, Demetrios; Worth, Laura L.; Chan, Ka Wah; Couriel, Daniel R.; Rondon, Gabriela; Sharma, Manish; Qazilbash, Muzaffar; Jones, Roy B.; Kebriaei, Partow; McMannis, John; Hosing, Chitra M.; Nieto, Yago; Champlin, Richard E.; Shpall, Elizabeth J.; de Lima, Marcos

    2014-01-01

    Unrelated cord blood transplantation (CBT) is an alternative treatment option for patients who lack a matched donor. However, the optimal type and intensity of the preparative regimen remains unclear. We evaluated the toxicity and outcomes of a conditioning regimen consisting of melphalan 140 mg/m2 (day −8), thiotepa 10 mg/kg (day −7), fludarabine 160 mg/m2 over 4 days (days −6 to −3), and rabbit ATG 1.25 mg/kg (day −4) and 1.75 mg/kg (day −3) (FMT). Forty-seven patients with advanced hematologic malignancies with a median age of 23 years (30 adults and 17 children) were treated. Sixty percent of patients were in remission at transplant. Ninety-one percent of the patients engrafted neutrophils after a median of 22 days, and all but one of the patients achieving donor engraftment had hematopoietic recovery with 100% cord blood-derived cells. Grade 3 gastrointestinal toxicity was the major non-hematopoietic toxicity occurring in 32% of patients. Cumulative incidence of day-100 grade II-IV aGVHD and cGVHD were 53% and 34%, respectively, and non-relapse mortality at day 100 and 2 years was 11% and 40%. Two-year disease-free and overall survival rates were 31% and 44%, respectively. These results suggest that FMT is a feasible conditioning regimen for patients undergoing CBT. PMID:21988645

  16. Effects of single-agent and combination chemotherapy for gestational trophoblastic tumors on risks of second malignancy and early menopause.

    PubMed

    Savage, Philip; Cooke, Rosie; O'Nions, Jenny; Krell, Jon; Kwan, Amy; Camarata, Michelle; Dancy, Gairin; Short, Dee; Seckl, Michael J; Swerdlow, Anthony

    2015-02-10

    To assess the risks of second malignancy and early menopause in a large cohort of patients with gestational trophoblastic tumor who were treated with chemotherapy. A survey of patients treated at Charing Cross Hospital between 1958 and 2000 was performed in 2006 to assemble incidence data for subsequent malignancies and the age at menopause. Treatment records were reviewed for the regimens and durations, and the incidence of subsequent malignancies was compared with that in the national age-matched population. Data were obtained for 1,903 patients, with a mean follow-up of 16.9 years. Eighty-six patients developed a subsequent malignancy compared with an expected number of 79 (standardized incidence ratio [SIR], 1.1; 95% CI, 0.9 to 1.3). The overall risk was low for patients treated with single-agent methotrexate and folinic acid (MTX-FA; SIR, 0.7; 95% CI, 0.5 to 1.1) and also for patients treated with etoposide, methotrexate, and dactinomycin followed by cyclophosphamide and vincristine on alternating weeks (EMA-CO) with an SIR of 0.9 (95% CI, 0.4 to 2.2), but there were significantly increased risks of oral cancer, melanoma, meningioma, and leukemia. The cumulative risk of early menopause was low after MTX-FA but was substantial after EMA-CO, reaching 13% by age 40 years and 36% by age 45 years. Subsequent cancer risks for patients cured of gestational trophoblastic tumors with modern chemotherapy appear similar to those of the normal population with no overall increased risk of malignancy after MTX-FA or EMA-CO. However, there was evidence of an increased risk of leukemia after EMA-CO and some evidence of other site-specific increased risks based on small patient numbers. All major treatments except MTX-FA increased the risk of early menopause. © 2014 by American Society of Clinical Oncology.

  17. Erythropoiesis-Stimulating Agent (ESA) Practice Patterns in Patients With Chemotherapy-Induced Anemia (CIA) Treated at Hospital Oncology Clinics.

    PubMed

    Reitan, John F; van Breda, Arletta; Shreay, Sanatan; Corey-Lisle, Patricia K; Cong, Ze

    2013-02-01

    To characterize erythropoiesis-stimulating agent (ESA) usage initiated in hospital outpatient oncology centers that employ weekly (QW) and every-3-week (Q3W) ESA dosing regimens; describe the frequency of ESA dosing, transfusions, hemoglobin determinations, and anemia-related visits between these 2 regimens; and compare the rates at which inpatient ESA doses are administered on QW versus Q3W schedules. This was a retrospective, observational record review evaluating ESA usage in 641 patients from 8 outpatient oncology clinics throughout the United States. Adult patients who initiated myelosuppressive chemotherapy for a documented solid tumor between August 1, 2007 and June 30, 2009 and received their first 3 consecutive outpatient ESA doses on a QW or Q3W schedule were eligible for study inclusion. During a single course of chemotherapy, ESA administrations were recorded as long as ESA therapy was continued on the initial regimen. ESA doses were captured until termination of ESA therapy, until 9 months had elapsed since the first ESA dose, until the patient was switched to another ESA regimen, or until death. ESA administration during inpatient admissions was also recorded. ESA utilization varied between the dosing groups, with fewer ESA doses administered per follow-up month in patients receiving Q3W versus QW ESA therapy (mean, 1 vs 2 doses). Compared to weekly administration, extended-dose ESA therapy also reduced the number of hemoglobin determinations and anemia-related visits without chemotherapy required per follow-up month. Neither the number of transfusions nor the number of packed red blood cell units administered per follow-up month differed between treatment groups. Compared to weekly ESA therapy, Q3W administration reduced costs associated with ESA prescribing and utilization. Extended-dose ESA therapy (Q3W dosing) may improve practice efficiency and may be associated with reduced frequencies of hemoglobin determinations and ESA doses required. Q3W

  18. Third-generation chemotherapy agents in the treatment of advanced non-small cell lung cancer: a meta-analysis.

    PubMed

    Baggstrom, Maria Q; Stinchcombe, Thomas E; Fried, Daniel B; Poole, Charles; Hensing, Thomas A; Socinski, Mark A

    2007-09-01

    To estimate the efficacy of third-generation (3G) chemotherapy agents (paclitaxel, docetaxel, gemcitabine, vinorelbine, and irinotecan) on response and survival in stage IIIB/IV non-small cell lung cancer (NSCLC). A meta-analysis was performed using trials identified through MEDLINE. Results on tumor response and survival were collected from randomized trials comparing 3G monotherapy versus best supportive care (BSC), 3G monotherapy versus second-generation (2G) platinum-based regimens, and 3G platinum-based regimens versus 2G platinum-based regimens. Of the 2480 citations screened, 20 randomized controlled trials fulfilled the inclusion and exclusion criteria, and 19 trials were used in the analyses. The data from two, three-arm trials were used in two different comparisons. Five trials (n = 1029 patients) compared 3G monotherapy with BSC. The summary risk difference (RD) for 1-year survival favored 3G agents by 7% (95% confidence interval [CI]: 2%, 12%). Four trials (n = 871 patients) compared treatment with 3G monotherapy versus 2G platinum-based regimens. The response RD was -6% (95% CI: -11%, 0%), and the 1-year survival rate RD was 3% (95% CI: -3%, 10%), suggesting that despite a slightly higher response rate for 2G platinum-based regimens relative to 3G monotherapy, there is equivalency in survival. Twelve trials (n = 3995) compared 3G versus 2G platinum-based regimens. The RD for response was 12% (95% CI: 10%, 15%). A RD for 1-year was not calculated, because of heterogeneity among the trials. A subset analysis of 3G versus 2G platinum-based doublets revealed a 1-year survival-rate RD of 6% (95% CI: 2%, 10%), favoring 3G platinum-based regimens without evidence of heterogeneity. 3G agents have been a significant advance in the treatment of NSCLC.

  19. Combination of chemotherapy and cancer stem cell targeting agents: Preclinical and clinical studies.

    PubMed

    Li, Yanyan; Atkinson, Katharine; Zhang, Tao

    2017-03-12

    The cancer stem cell model claims that the initiation, maintenance, and growth of a tumor are driven by a small population of cancer cells termed cancer stem cells. Cancer stem cells possess a variety of phenotypes associated with therapeutic resistance and often cause recurrence of the diseases. Several strategies have been investigated to target cancer stem cells in a variety of cancers, such as blocking one or more self-renewal signaling pathways, reducing the expression of drug efflux and ATP-binding cassette efflux transporters, modulating epigenetic aberrations, and promoting cancer stem cell differentiation. A number of cell and animal studies strongly support the potential benefits of combining chemotherapeutic drugs with cancer stem cell targeting agents. Clinical trials are still underway to address the pharmacokinetics, safety, and efficacy of combination treatment. This mini-review provides an updated discussion of these preclinical and clinical studies.

  20. Chemotherapy Studies on Schistosomiasis.

    DTIC Science & Technology

    Schistosoma mansoni, *Chemotherapy, *Prophylaxis, Preventive medicine, Mice, Drugs, Brazil , Laboratory tests, Snails, Cercariae, Tropical medicine, Selection, Parasitology, Schistosomiasis, Chemotherapeutic agents, Medical research

  1. Intracavitary chemotherapy

    SciTech Connect

    Markman, M.

    1985-01-01

    Pharmacokinetic modeling has suggested, and clinical investigations have confirmed, that intracavitary drug administration can result in a much greater drug exposure for the cavity into which the agent is instilled compared to the plasma. Both the safety and the efficacy of several agents administered individually or in combination have now been demonstrated. Several malignancies, in particular ovarian carcinoma and malignant mesothelioma, which remain confined to body cavities for much of their natural history, might be most rationally treated by the intracavitary treatment approach. Early clinical trials have demonstrated significant activity of intracavitary chemotherapy in both of these malignancies. Optimal drugs and dosages as well as appropriate scheduling for the various tumors involving body cavities remain to be defined. Whether or not combination intracavitary chemotherapy will significantly improve survival of patients with malignant disease confined to body cavities must await carefully controlled clinical trials comparing this treatment approach to standard systemically administered chemotherapy. 144 references.

  2. Stability of antineoplastic agents in use for home-based intravenous chemotherapy.

    PubMed

    Benizri, Frédéric; Bonan, Brigitte; Ferrio, Anne-Laure; Brandely, Marie-Laure; Castagné, Vincent; Théou-Anton, Nathalie; Verlinde-Carvalho, Muriel; Havard, Laurent

    2009-02-01

    The aim of this work was first to define which antineoplastic agents with sufficiently long stability could be eligible in the circuit of home-based therapy (centralised preparation, transport to the patient's home and administration by nurses) and, second, to propose a standardisation of the stability data of anticancer drugs in use for home hospitalisation. A survey carried out in six hospital pharmacies of the Assistance Publique-Hôpitaux de Paris (AP-HP) hospitals, with important activity in oncology, listed the stability data used locally by each site. The final goal is to reach a consensus for the stability of cytotoxic drugs, which was the result of an original collaboration between the pharmacists of the compounding unit and the quality control unit. These results were compared to marketing authorisation data. The survey showed that eight antineoplastic agents of 34 were prepared under identical conditions (infusion diluent, concentration range, protection from light, temperature) by all hospitals (3 < or = n < or = 6): the stability was identical between each site for only two cytotoxic drug preparations (fotemustine and gemcitabine) and varied by up to 168 h or 7 days for the preparations of dacarbazine, epirubicine and cisplatin. Stability validated by pharmacists and those provided by marketing authorisation ranged respectively from "extemporaneously prepared" at 1,344 h (median = 168 h) to "extemporaneously prepared" at 720 h (median = 4 h). For 11 antineoplastic drugs, no information about the stability after compounding was specified in the marketing authorisation. Of all cytotoxic drugs used in the Hospital at Home of AP-HP, stability after compounding validated by pharmacists was less than 30 h for six of them, between 30 and 78 h for four and exceeding 78 h for the remaining 24. Considering the lack of data about cytotoxic drugs stability provided by the pharmaceutical companies and the difficulties in retrieving and interpreting the literature

  3. Self-assembled nanoplatform for targeted delivery of chemotherapy agents via affinity-regulated molecular interactions.

    PubMed

    Park, Spencer; Kang, Sungkwon; Veach, Alexander J; Vedvyas, Yogindra; Zarnegar, Rasa; Kim, Ju-Young; Jin, Moonsoo M

    2010-10-01

    Site-specific delivery of drugs while minimizing unwanted distribution has been one of the pursued goals in cancer therapy. In this endeavor, we have developed targeted polymeric nanoparticles called amphiphilic urethane acrylate nonionomer (UAN) for encapsulation of diverse water-insoluble drugs and diagnostic agents, as well as for simple and reproducible surface conjugation of targeting ligands. Using monoclonal antibodies or lymphocyte function-associated antigen-1 (LFA-1) I domain engineered for varying affinities to intercellular adhesion molecule (ICAM)-1, we were able to deliver UAN nanoparticles to human cancer cells with the efficiency dependent on the strength of the molecular interactions and the degree of ICAM-1 expression on cell surface. Compared to non-specific uptake of free drugs, targeted delivery of UAN nanoparticles carrying equal amount of drugs produced more potent cytotoxicity. Notably, without the targeting ligands attached, UAN nanoparticles were largely precluded from non-specific uptake by the cells, resulting in much lower toxicity. The versatility of our UAN nanoparticles in both payload encapsulation and presentation of targeting ligands may facilitate developing a robust platform for evaluating various combinations of cancer drugs and molecular interactions toward developing effective cancer therapy formulations.

  4. Microtubule-Targeting Agents Eribulin and Paclitaxel Differentially Affect Neuronal Cell Bodies in Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Benbow, Sarah J; Wozniak, Krystyna M; Kulesh, Bridget; Savage, April; Slusher, Barbara S; Littlefield, Bruce A; Jordan, Mary Ann; Wilson, Leslie; Feinstein, Stuart C

    2017-04-08

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anticancer treatment with microtubule-targeted agents (MTAs). The frequency of severe CIPN, which can be dose limiting and even life threatening, varies widely among different MTAs. For example, paclitaxel induces a higher frequency of severe CIPN than does eribulin. Different MTAs also possess distinct mechanisms of microtubule-targeted action. Recently, we demonstrated that paclitaxel and eribulin differentially affect sciatic nerve axons, with paclitaxel inducing more pronounced neurodegenerative effects and eribulin inducing greater microtubule stabilizing biochemical effects. Here, we complement and extend these axonal studies by assessing the effects of paclitaxel and eribulin in the cell bodies of sciatic nerve axons, housed in the dorsal root ganglia (DRG). Importantly, the microtubule network in cell bodies is known to be significantly more dynamic than in axons. Paclitaxel induced activating transcription factor 3 expression, a marker of neuronal stress/injury. Paclitaxel also increased expression levels of acetylated tubulin and end binding protein 1, markers of microtubule stability and growth, respectively. These effects are hypothesized to be detrimental to the dynamic microtubule network within the cell bodies. In contrast, eribulin had no significant effect on any of these parameters in the cell bodies. Taken together, DRG cell bodies and their axons, two distinct neuronal cell compartments, contain functionally distinct microtubule networks that exhibit unique biochemical responses to different MTA treatments. We hypothesize that these distinct mechanistic actions may underlie the variability seen in the initiation, progression, persistence, and recovery from CIPN.

  5. Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe.

    PubMed

    Campone, Mario; Yang, Hongbo; Faust, Elizabeth; Kageleiry, Andrew; Signorovitch, James E; Zhang, Jie; Gao, Haitao

    2014-12-01

    Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE + EXE). This study estimates the costs of managing adverse events (AEs) during EVE + EXE therapy and single-agent chemotherapy in Western Europe. An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE + EXE or chemotherapies. AE rates for patients receiving EVE + EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€). The EVE + EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE + EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively. The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE + EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.

  6. SMAC mimetic (JP1201) sensitizes non-small cell lung cancers to multiple chemotherapy agents in an IAP dependent but TNFα independent manner

    PubMed Central

    Greer, Rachel M.; Peyton, Michael; Larsen, Jill E.; Girard, Luc; Xie, Yang; Gazdar, Adi; Harran, Patrick; Wang, Lai; Brekken, Rolf A.; Wang, Xiaodong; Minna, John D.

    2012-01-01

    Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are inhibited by the second mitocondrial activator of caspases (SMAC). Previously, a small subset of TNFα-expressing non-small cell lung cancers (NSCLCs) was found to be sensitive to SMAC mimetics alone. In this study we determined if a SMAC mimetic (JP1201) could sensitize non-responsive NSCLC cell lines to standard chemotherapy. We found that JP1201 sensitized NSCLCs to doxorubicin, erlotinib, gemcitabine, paclitaxel, vinorelbine, and the combination of carboplatin with paclitaxel in a synergistic manner at clinically achievable drug concentrations. Sensitization did not occur with platinum alone. Furthermore, sensitization was specific for tumor compared to normal lung epithelial cells, increased in NSCLCs harvested after chemotherapy treatment, and did not induce TNFα secretion. Sensitization also was enhanced in vivo with increased tumor inhibition and increased survival of mice carrying xenografts. These effects were accompanied by caspase 3, 4, and 9 activation, indicating that both mitochondrial and ER stress-induced apoptotic pathways are activated by the combination of vinorelbine and JP1201. Chemotherapies that induce cell death through the mitochondrial pathway required only inhibition of XIAP for sensitization, while chemotherapies that induce cell death through multiple apoptotic pathways required inhibition of cIAP1, cIAP2, and XIAP. Therefore, the data suggest that IAP-targeted therapy using a SMAC mimetic provides a new therapeutic strategy for synergistic sensitization of NSCLCs to standard chemotherapy agents, which appears to occur independently of TNFα secretion. PMID:22049529

  7. Chemotherapy versus Hypomethylating Agents for the Treatment of Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndrome after Allogeneic Stem Cell Transplant.

    PubMed

    Motabi, Ibraheem H; Ghobadi, Armin; Liu, Jingxia; Schroeder, Mark; Abboud, Camille N; Cashen, Amanda F; Stockler-Goldstein, Keith E; Uy, Geoffrey L; Vij, Ravi; Westervelt, Peter; DiPersio, John F

    2016-07-01

    Allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). For patients with relapsed disease after transplantation, intensive chemotherapy followed by donor lymphocyte infusion (DLI) or a second allo-SCT may result in a durable response in some patients. High-intensity chemotherapy and less aggressive therapy with hypomethylating agents (HAs) with and without DLI are often used for relapse after allo-SCT. Here we compared the treatment outcomes of intensive chemotherapy with that of HAs in relapsed AML and MDS after allo-SCT. Patients who had received a second SCT within 90 days of the relapse date were excluded. The primary endpoints were overall response rate (ORR) and overall survival (OS). Secondary endpoints were complete remission (CR) rate and progression-free survival (PFS). One hundred patients were included: 73 patients received chemotherapy and 27 patients received an HA. Fifty-six percent of patients in the chemotherapy group and 33% of patients in the HA group received at least 1 DLI after treatment. Treatment with chemotherapy resulted in a higher ORR (51% versus 19%, P = .004) and a higher CR rate (40% versus 7%, P = .002). The median OS (6 versus 3.9 months, P = .01) and PFS (4.9 versus 3.8 months, P = .02) were longer in the chemotherapy group. Similar benefit of chemotherapy over HAs was maintained in all treatment outcomes after controlling for the use of DLI. The use of chemotherapy followed by DLI offered the greatest benefit (ORR, 68%; CR, 59%, 1-year OS, 44%; and median OS, 9.8 months). In conclusion, in our hands, with limited numbers, the use of more conventional salvage chemotherapy, with DLI when possible, for the treatment of relapsed AML and MDS after allo-SCT is associated with better outcomes than nonchemotherapy (HA) options.

  8. Treatment of chemotherapy-induced anemia in ovarian cancer patients: does the use of erythropoiesis-stimulating agents worsen survival?

    PubMed

    Rocconi, Rodney P; Sullivan, Paula; Long, Beverly; Blaize, Marie; Brown, Jennifer; Arbuckle, Janeen; Bevis, Kerri; Estes, Jacob M; Reed, Eddie; Finan, Michael A

    2012-06-01

    Considering the paucity of data relating erythropoiesis-stimulating agent (ESA) use to ovarian cancer survival, our objective was to evaluate the effect of ESA as used for the treatment of chemotherapy-induced anemia (CIA) on survival in ovarian cancer patients. A multi-institution retrospective chart review was performed on ovarian cancer patients. Data collection included patient demographic, surgicopathologic, chemotherapy, ESA, and survival data. Patients were stratified by ever-use of ESA and were compared using appropriate statistical methods. A total of 581 patients were eligible for analysis with 39% (n = 229) patients with ever-use of ESA (ESA-YES) and 61% (n = 352) never-use ESA (ESA-NO). Mean age was 60.4 years with most patients having stage IIIC (60%) of papillary serous histological diagnosis (64%) with an optimal cytoreduction (67%). Median follow-up for the cohort was 27 months. Both ESA-YES and ESA-NO groups were similar regarding age, body mass index, race, stage, histological diagnosis, and debulking status. Compared with the ESA-NO group, ESA-YES patients were significantly more likely to experience recurrence (56% vs 80%, P < 0.001) and death (46% vs 59%, P = 0.002). Kaplan-Meier curves demonstrated a significant reduction in progression-free survival for ESA-YES patients (16 vs 24 months, P < 0.001); however, overall survival was statistically similar between the 2 groups (38 vs 46 months, P = 0.10). When stratifying by ever experiencing a CIA, ESA-YES patients demonstrated a significantly worse progression-free survival (17 vs 24 months, P = 0.02) and overall survival (37 vs 146 months, P < 0.001). Our data evaluating the use of ESA as a treatment of CIA in ovarian cancer patients are similar to reports in other tumor sites. Considering that patients who used ESA were more likely to experience recurrence and death and to have decreased survival, the use of ESA in ovarian cancer patients should be limited.

  9. Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease.

    PubMed

    Lee, Young Jae; Park, Jeong Yeol; Kim, Dae Yeon; Suh, Dae Shik; Kim, Jong Hyeok; Kim, Yong Man; Kim, Young Tak; Nam, Joo Hyun

    2017-03-01

    The aim of this study was to compare responses to single-agent chemotherapies and evaluate the predictive factors of resistance in low risk (LR) gestational trophoblastic disease (GTD). The chemotherapy agents included methotrexate (MTX) and actinomycin D (ACT-D). We conducted a retrospective study of 126 patients with GTD who were treated between 2000 and 2013. A total of 71 patients with LR GTD were treated with MTX (8-day regimen or weekly regimen, n=53) or ACT-D (bi-weekly pulsed regimen or 5-day regimen, n=18). The successful treatment group and the failed treatment group were compared and analyzed to identify prognostic factors. The complete response rates were 83.3% for ACT-D and 62.2% for MTX, with no statistically significant difference. There was no severe adverse effect reported for either group. Longer interval durations from the index pregnancy (>2 months, p=0.040) and larger tumor size (>3 cm, p=0.020) were more common in non-responders than in responders; these results were statistically significant. Based on our results, ACT-D may be a better option than MTX as a first-line single chemotherapy agent for LR GTD. The bi-weekly pulsed ACT-D regimen had minimal, or at least the same, toxicities compared with MTX. However, due to the lack of strong supporting evidence, it cannot be conclusively stated that this is the best single agent for first-line chemotherapy in LR GTD patients. Further larger controlled trials will be necessary to establish the best guidelines for GTD treatment.

  10. Comparing and evaluating the efficacy of methotrexate and actinomycin D as first-line single chemotherapy agents in low risk gestational trophoblastic disease

    PubMed Central

    Kim, Dae-Yeon; Suh, Dae-Shik; Kim, Jong-Hyeok; Kim, Young-Tak

    2017-01-01

    Objective The aim of this study was to compare responses to single-agent chemotherapies and evaluate the predictive factors of resistance in low risk (LR) gestational trophoblastic disease (GTD). The chemotherapy agents included methotrexate (MTX) and actinomycin D (ACT-D). Methods We conducted a retrospective study of 126 patients with GTD who were treated between 2000 and 2013. A total of 71 patients with LR GTD were treated with MTX (8-day regimen or weekly regimen, n=53) or ACT-D (bi-weekly pulsed regimen or 5-day regimen, n=18). The successful treatment group and the failed treatment group were compared and analyzed to identify prognostic factors. Results The complete response rates were 83.3% for ACT-D and 62.2% for MTX, with no statistically significant difference. There was no severe adverse effect reported for either group. Longer interval durations from the index pregnancy (>2 months, p=0.040) and larger tumor size (>3 cm, p=0.020) were more common in non-responders than in responders; these results were statistically significant. Conclusion Based on our results, ACT-D may be a better option than MTX as a first-line single chemotherapy agent for LR GTD. The bi-weekly pulsed ACT-D regimen had minimal, or at least the same, toxicities compared with MTX. However, due to the lack of strong supporting evidence, it cannot be conclusively stated that this is the best single agent for first-line chemotherapy in LR GTD patients. Further larger controlled trials will be necessary to establish the best guidelines for GTD treatment. PMID:27819410

  11. Efficacy and safety of single agent or combination adjuvant chemotherapy in elderly patients with colon cancer: a Canadian cancer institute experience.

    PubMed

    Kim, Christina A K; Spratlin, Jennifer L; Armstrong, Dawn E; Ghosh, Sunita; Mulder, Karen E

    2014-09-01

    The pattern of adjuvant chemotherapy (AC) use, toxicity profile, and survival benefit in elderly patients with colon cancer (CC) is unclear. We sought to (1) determine whether patients ≥ 65 years with stage III CC were offered single-agent or combination AC, (2) evaluate the reason for selecting single-agent versus combination AC, (3) evaluate the toxicity profile of single-agent and combination AC in the elderly, and (4) determine whether a survival benefit exists for elderly patients receiving combination AC. A retrospective analysis of records of patients ≥ 65 years diagnosed with stage III CC from 2004 to 2010 was performed to identify baseline characteristics, AC protocols, toxicity, dose intensity, and survival. Two hundred sixty-eight patients ≥ 65 years were diagnosed and treated with AC from 2004 to 2010. Of these patients, 178 were treated with single-agent AC and 90 were treated with combination AC. The most common reasons for choosing single-agent AC were patient preference, comorbidities, and lack of drug coverage. For each year over 65 years, the odds of receiving combination over single-agent AC decreased by 22%. There were more dose delays, dose reductions, and early chemotherapy discontinuation in the combination AC group because of hematologic toxicity. The 5-year overall survival (OS) was 73% in patients who received single-agent AC compared with 84% in those who received combination AC. There was no difference in cancer-related deaths between the groups. In elderly patients treated with AC for stage III CC, single-agent AC is used more frequently than combination AC, based on age, comorbidities, and patient choice. Toxicity with combination AC in elderly patients is high. No survival benefit was seen with combination AC over single-agent AC. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Metronomic chemotherapy

    PubMed Central

    Maiti, Rituparna

    2014-01-01

    Toxic effects and chemoresistance are major hurdles in chemotherapy and to avoid these problems caused by traditional chemotherapeutic regimens, a new modality of drug administration called “metronomic chemotherapy” has emerged. Such regimen involves the frequent administration of conventional chemotherapeutic agents at very low doses to target activated endothelial cells in tumors, the advantages of which include minimal adverse effects and a rare chance of developing acquired drug resistance. Previously it was thought that they act by targeting angiogenesis, but recently additional mechanisms have been discovered which has established metronomic chemotherapy as a type of multi-targeted therapy. The knowledge gained from the preclinical studies of metronomic chemotherapy, along with clinical experience, will help to design better therapeutic protocols against cancer. Detailed pharmacogenomic and pharmacoproteomic studies on tumor endothelial cells and large multi-centered clinical trials, integrating bio-marker analyzes, are needed to investigate and validate the best treatment combinations for each tumor type and patient population. PMID:25210398

  13. A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer.

    PubMed

    Cetina, Lucely; Crombet, Tania; Jiménez-Lima, Roberto; Zapata, Sergio; Ramos, Mayra; Avila, Sandra; Coronel, Jaime; Charco, Eduardo; Bojalil, Rafael; Astudillo, Horacio; Bazán, Blanca; Dueñas-González, Alfonso

    2015-01-01

    Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m(2) as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m(2)) or cisplatin (50 mg/m(2)) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5-96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were 163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.

  14. 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.

  15. A pilot study of nimotuzumab plus single agent chemotherapy as second- or third-line treatment or more in patients with recurrent, persistent or metastatic cervical cancer

    PubMed Central

    Cetina, Lucely; Crombet, Tania; Jiménez-Lima, Roberto; Zapata, Sergio; Ramos, Mayra; Avila, Sandra; Coronel, Jaime; Charco, Eduardo; Bojalil, Rafael; Astudillo, Horacio; Bazán, Blanca; Dueñas-González, Alfonso

    2015-01-01

    Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m2 as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m2) or cisplatin (50 mg/m2) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5–96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer. PMID:25802932

  16. Metronomic chemotherapy.

    PubMed

    Mutsaers, Anthony J

    2009-08-01

    Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

  17. Testing chemotherapeutic agents in the feather follicle identifies a selective blockade of cell proliferation and a key role for sonic hedgehog signaling in chemotherapy-induced tissue damage.

    PubMed

    Xie, Guojiang; Wang, Hangwei; Yan, Zhipeng; Cai, Linyan; Zhou, Guixuan; He, Wanzhong; Paus, Ralf; Yue, Zhicao

    2015-03-01

    Chemotherapeutic agents induce complex tissue responses in vivo and damage normal organ functions. Here we use the feather follicle to investigate details of this damage response. We show that cyclophosphamide treatment, which causes chemotherapy-induced alopecia in mice and man, induces distinct defects in feather formation: feather branching is transiently and reversibly disrupted, thus leaving a morphological record of the impact of chemotherapeutic agents, whereas the rachis (feather axis) remains unperturbed. Similar defects are observed in feathers treated with 5-fluorouracil or taxol but not with doxorubicin or arabinofuranosyl cytidine (Ara-C). Selective blockade of cell proliferation was seen in the feather branching area, along with a downregulation of sonic hedgehog (Shh) transcription, but not in the equally proliferative rachis. Local delivery of the Shh inhibitor, cyclopamine, or Shh silencing both recapitulated this effect. In mouse hair follicles, those chemotherapeutic agents that disrupted feather formation also downregulated Shh gene expression and induced hair loss, whereas doxorubicin or Ara-C did not. Our results reveal a mechanism through which chemotherapeutic agents damage rapidly proliferating epithelial tissue, namely via the cell population-specific, Shh-dependent inhibition of proliferation. This mechanism may be targeted by future strategies to manage chemotherapy-induced tissue damage.

  18. In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers

    PubMed Central

    Lu, Qing-Bin; Zhang, Qin-Rong; Ou, Ning; Wang, Chun-Rong; Warrington, Jenny

    2015-01-01

    Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers. PMID:26351651

  19. Treosulfan-thiotepa-fludarabine-based conditioning regimen for allogeneic transplantation in patients with thalassemia major: a single-center experience from north India.

    PubMed

    Choudhary, Dharma; Sharma, Sanjeev Kumar; Gupta, Nitin; Kharya, Gaurav; Pavecha, Punita; Handoo, Anil; Setia, Rasika; Katewa, Satyendra

    2013-03-01

    Hematopoietic stem cell transplantation (HSCT) is the definite treatment for patients with thalassemia major. A busulfan (Bu) and cyclophosphamide (Cy)-based regimen has been the standard myeloablative chemotherapy, but it is associated with higher treatment-related toxicity, particularly in patients classified as high risk by the Pesaro criteria. Treosulfan-based conditioning regimens have been found to be equally effective and less toxic. Consequently, we analyzed the safety and efficacy of treosulfan/thiotepa/fludarabine (treo/thio/flu)-based conditioning regimens for allogeneic HSCT in patients with thalassemia major between February 2010 and September 2012. We compared those results retrospectively with results in patients who underwent previous HSCT with a Bu/Cy/antithymocyte globulin (ATG)-based conditioning regimen. A treo/thio/flu-based conditioning regimen was used in 28 consecutive patients with thalassemia major. The median patient age was 9.7 years (range, 2-18 years), and the mean CD34(+) stem cell dose was 6.18 × 10(6)/kg. Neutrophil and platelet engraftment occurred at a median of 15 days (range, 12-23 days) and 21 days (range, 14-34 days), respectively. Three patients developed veno-occlusive disease, 4 patients developed acute graft-versus-host disease (GVHD), and 2 patients had chronic GVHD. Treatment-related mortality (TRM) was 21.4%. Two patients experienced secondary graft rejection. We compared these results with results in patients who underwent previous HSCT using a Bu/Cy/ATG-based conditioning regimen. Twelve patients were treated with this protocol, at a median age of 7.2 years (range, 2-11 years). One patient had moderate veno-occlusive disease, 2 patients developed acute GVHD, 2 patients had chronic GVHD, and 2 patients experienced graft rejection. There was no TRM in this group. We found no significant differences between the 2 groups (treo/thio/flu vs Bu/Cy/ATG) in terms of the incidence of acute GVHD, chronic GVHD, TRM, and graft

  20. Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

    PubMed

    Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

    2017-05-01

    AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. SMAC mimetic (JP1201) sensitizes non-small cell lung cancers to multiple chemotherapy agents in an IAP-dependent but TNF-α-independent manner.

    PubMed

    Greer, Rachel M; Peyton, Michael; Larsen, Jill E; Girard, Luc; Xie, Yang; Gazdar, Adi F; Harran, Patrick; Wang, Lai; Brekken, Rolf A; Wang, Xiaodong; Minna, John D

    2011-12-15

    Inhibitors of apoptosis proteins (IAP) are key regulators of apoptosis and are inhibited by the second mitocondrial activator of caspases (SMAC). Previously, a small subset of TNF-α-expressing non-small cell lung cancers (NSCLC) was found to be sensitive to SMAC mimetics alone. In this study, we determined if a SMAC mimetic (JP1201) could sensitize nonresponsive NSCLC cell lines to standard chemotherapy. We found that JP1201 sensitized NSCLCs to doxorubicin, erlotinib, gemcitabine, paclitaxel, vinorelbine, and the combination of carboplatin with paclitaxel in a synergistic manner at clinically achievable drug concentrations. Sensitization did not occur with platinum alone. Furthermore, sensitization was specific for tumor compared with normal lung epithelial cells, increased in NSCLCs harvested after chemotherapy treatment, and did not induce TNF-α secretion. Sensitization also was enhanced in vivo with increased tumor inhibition and increased survival of mice carrying xenografts. These effects were accompanied by caspase 3, 4, and 9 activation, indicating that both mitochondrial and endoplasmic reticulum stress-induced apoptotic pathways are activated by the combination of vinorelbine and JP1201. Chemotherapies that induce cell death through the mitochondrial pathway required only inhibition of X-linked IAP (XIAP) for sensitization, whereas chemotherapies that induce cell death through multiple apoptotic pathways required inhibition of cIAP1, cIAP2, and XIAP. Therefore, the data suggest that IAP-targeted therapy using a SMAC mimetic provides a new therapeutic strategy for synergistic sensitization of NSCLCs to standard chemotherapy agents, which seems to occur independently of TNF-α secretion.

  2. Vorinostat, a histone deacetylase (HDAC) inhibitor, promotes cell cycle arrest and re-sensitizes rituximab- and chemo-resistant lymphoma cells to chemotherapy agents.

    PubMed

    Xue, Kai; Gu, Juan J; Zhang, Qunling; Mavis, Cory; Hernandez-Ilizaliturri, Francisco J; Czuczman, Myron S; Guo, Ye

    2016-02-01

    Preclinical models of chemotherapy resistance and clinical observations derived from the prospective multicenter phase III collaborative trial in relapsed aggressive lymphoma (CORAL) study demonstrated that primary refractory/relapsed B cell diffuse large B cell lymphoma has a poor clinical outcome with current available second-line treatments. Preclinically, we found that rituximab resistance is associated with a deregulation on the mitochondrial potential rendering lymphoma cells resistant to chemotherapy-induced apoptotic stimuli. There is a dire need to develop agents capable to execute alternative pathways of cell death in an attempt to overcome chemotherapy resistance. Posttranscriptional histone modification plays an important role in regulating gene transcription and is altered by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs regulate several key cellular functions, including cell proliferation, cell cycle, apoptosis, angiogenesis, migration, antigen presentation, and/or immune regulation. Given their influence in multiple regulatory pathways, HDAC inhibition is an attractive strategy to evaluate its anti-proliferation activity in cancer cells. To this end, we studied the anti-proliferation activity and mechanisms of action of suberoylanilide hydroxamic acid (SAHA, vorinostat) in rituximab-chemotherapy-resistant preclinical models. A panel of rituximab-chemotherapy-sensitive (RSCL) and rituximab-chemotherapy-resistant cell lines (RRCL) and primary tumor cells isolated from relapsed/refractory B cell lymphoma patients were exposed to escalating doses of vorinostat. Changes in mitochondrial potential, ATP synthesis, and cell cycle distribution were determined by Alamar blue reduction, Titer-Glo luminescent assays, and flow cytometric, respectively. Protein lysates were isolated from vorinostat-exposed cells, and changes in members of Bcl-2 family, cell cycle regulatory proteins, and the acetylation status of histone H3 were

  3. Effect of chemotherapy with alkylating agents on the yield of CD34+ cells in patients with multiple myeloma. Results of the Spanish Myeloma Group (GEM) Study.

    PubMed

    de la Rubia, Javier; Bladé, Joan; Lahuerta, Juan-José; Ribera, Josep M; Martínez, Rafael; Alegre, Adrián; García-Laraña, José; Fernández, Pascual; Sureda, Anna; de Arriba, Felipe; Carrera, Dolores; Besalduch, Joan; García Boyero, Raimundo; Palomera Bernal, Luis; Hernández, Miguel T; García, Paz Ribas; Pérez-Calvo, Javier; Alcalá, Antonio; Casado, Luis Felipe; San Miguel, Jesús

    2006-05-01

    Although alkylating agents are clearly beneficial in multiple myeloma (MM), their deleterious effect on bone marrow hematopoietic progenitor cells usually precludes their use as front-line therapy in patients scheduled to undergo autologous stem cell transplantation (ASCT). We analyzed the impact of first-line chemotherapy with alkylating agents on stem cell collection in MM patients. Seven hundred and eighty-nine patients included in the Spanish multicenter protocol GEM-2000 underwent mobilization therapy after four courses of alternating VBMCP/VBAD chemotherapy. The mobilization regimens consisted of standard or high-dose granulocyte colony-stimulating factor (G-CSF) in 551 (70%) patients, and chemotherapy and G-CSF in 206 (26%) patients. The CD34+ cell yield was lower than 4x10(6)/kg in 388 patients (49%), and equal or greater than 4x10(6)/kg in 401 patients (51%). Multivariate analysis indicated that advanced age (p<0.0001) and longer interval between diagnosis and mobilization (p=0.012) were the two variables associated with a lower CD34+ cell yield. Significant differences in CD34+ cell yield were not observed between the mobilization regimens. Of the 789 patients included in the protocol, 726 (92%) underwent the planned ASCT, whereas 25 (3%) patients did not because of the low number of CD34+ cells collected. Following ASCT, 0.5x10(9) neutrophils/L could be recovered after 11 days (median time; range, 5-71 days) and 20x10(9) platelets/L could be recovered after 12 days (median time; range, 6-69 days). A short-course of therapy with alkylating agents according to the GEM-2000 protocol was associated with an appropriate CD34+ cell collection, and allowed the planned ASCT to be performed in the majority of MM patients.

  4. Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells

    PubMed Central

    Owen, Sioned; Zhao, Huishan; Dart, Alwyn; Wang, Yamei; Ruge, Fiona; Gao, Yong; Wei, Cong; Wu, Yiling; Jiang, Wen G.

    2016-01-01

    Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP27. PMID:27600495

  5. Heat shock protein 27 is a potential indicator for response to YangZheng XiaoJi and chemotherapy agents in cancer cells.

    PubMed

    Owen, Sioned; Zhao, Huishan; Dart, Alwyn; Wang, Yamei; Ruge, Fiona; Gao, Yong; Wei, Cong; Wu, Yiling; Jiang, Wen G

    2016-11-01

    Heat shock protein 27 (HSP27) is a member of the heat shock protein family which has been linked to tumour progression and, most interestingly, to chemotherapy resistance in cancer patients. The present study examined the potential interplay between HSP27 and YangZheng XiaoJi, a traditional Chinese medicine used in cancer treatment. A range of cell lines from different tumour types including pancreatic, lung, gastric, colorectal, breast, prostate and ovarian cancer (both wild-type and resistant) were used. Levels and activation of HSP27 and its potential associated signalling pathways were evaluated by protein array and western blotting. Knockdown of HSP27 in cancer cells was achieved using siRNA. Localisation and co-localisation of HSP27 and other proteins were carried out by immunofluorescence. Cell growth and migration were evaluated in their response to a range of chemotherapeutic agents. The present study first identified, by way of protein array, that YangZheng XiaoJi was able to inhibit the phosphorylation of HSP27 protein in cancer cells. We further demonstrated that HSP27, which is co-localised with caspase-9, can be blocked from localising in focal adhesions and co-localising with caspase-9 by YangZheng XiaoJi. The study also demonstrated that YangZheng XiaoJi was able to sensitise cancer cells including those cells that were resistant to chemotherapy, to chemotherapeutic agents. Finally, knocking down HSP27 markedly reduced the migration of cancer cells and increased the sensitivity of cancer cells to the inhibitory effect on cellular migration by YangZheng XiaoJi. YangZheng XiaoJi can act as an agent in first sensitising cancer cells to chemotherapy and secondly to overcome, to some degree, chemoresistance when used in an appropriate fashion in patients who have active HSP27.

  6. Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual meeting. Part 2. 12-15 September 2009, San Francisco, CA, USA.

    PubMed

    Turner, Ben; Murch, Lisa

    2009-11-01

    The Interscience Conference on Antimicrobial Agents and Chemotherapy held in San Francisco included topics covering new therapeutic developments for the treatment of infectious diseases. This conference report highlights selected presentations on several antibiotics in development including a broad-spectrum penem beta-lactam antibiotic, a novel siderophore monobactam, as well as other novel antibiotics. Investigational drugs discussed include sulopenem and sulopenem etzadroxil (both Pfizer Inc), BAL-30072 (Basilea Pharmaceutica International Ltd), TP-120 and TP-787 (both Tetraphase Pharmaceuticals Inc), NAI-107 (New Anti Infectives Consortium/NexThera Biosciences) and ABI-200 (AdRem Biotech/US Department of Agriculture).

  7. Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment

    PubMed Central

    Pasquier, Eddy; Ciccolini, Joseph; Carre, Manon; Giacometti, Sarah; Fanciullino, Raphaelle; Pouchy, Charlotte; Montero, Marie-Pierre; Serdjebi, Cindy; Kavallaris, Maria; André, Nicolas

    2011-01-01

    Recent clinical evidence revealed that the use of beta-blockers such as propranolol, prior to diagnosis or concurrently with chemotherapy, could increase relapse-free and overall survival in breast cancer patients. We therefore hypothesized that propranolol may be able to increase the efficacy of chemotherapy either through direct effects on cancer cells or via anti-angiogenic mechanisms. In vitro proliferation assay showed that propranolol (from 50-100 μM) induces dose-dependent anti-proliferative effects in a panel of 9 human cancer and “normal” cell lines. Matrigel assays revealed that propranolol displays potent anti-angiogenic properties at non-toxic concentrations (<50 μM) but exert no vascular-disrupting activity. Combining chemotherapeutic drugs, such as 5-fluorouracil (5-FU) or paclitaxel, with propranolol at the lowest effective concentration resulted in synergistic, additive or antagonistic effects on cell proliferation in vitro depending on the cell type and the dose of chemotherapy used. Interestingly, breast cancer and vascular endothelial cells were among the most responsive to these combinations. Furthermore, Matrigel assays indicated that low concentrations of propranolol (10 – 50 μM) potentiated the anti-angiogenic effects of 5-FU and paclitaxel. Using an orthotopic xenograft model of triple-negative breast cancer, based on injection of luciferase-expressing MDA-MB-231 cells in the mammary fat pad of nude mice, we showed that propranolol, when used alone, induced only transient anti-tumor effects, if at all, and did not increase median survival. However, the combination of propranolol with chemotherapy resulted in more profound and sustained anti-tumor effects and significantly increased the survival benefits induced by chemotherapy alone (+19% and +79% in median survival for the combination as compared with 5-FU alone and paclitaxel alone, respectively; p<0.05). Collectively our results show that propranolol can potentiate the anti

  8. Shortened intensified multi-agent chemotherapy and non-cross resistant maintenance therapy for advanced lymphoblastic lymphoma in children and adolescents: report from the Children's Oncology Group.

    PubMed

    Abromowitch, Minnie; Sposto, Richard; Perkins, Sherrie; Zwick, David; Siegel, Stuart; Finlay, Jonathan; Cairo, Mitchell S

    2008-10-01

    Pediatric lymphoblastic lymphoma (LL) has utilized treatment strategies similar to childhood acute lymphoblastic leukaemia (ALL) with prolonged maintenance chemotherapy. We report the results of a pilot study to estimate the feasibility, toxicity and efficacy of a 12-month aggressive multi-agent chemotherapy regimen in children and adolescents with advanced LL. Between July 1994 and June 1997, 85 eligible children and adolescents with advanced LL (Stage III/IV) were enrolled on this pilot study. Patients achieving a complete response following induction and consolidation received six cycles of maintenance chemotherapy for a total duration of 12 months. Grade III/IV toxicities included: hematological (80%), infections (20%), stomatitis and elevated transaminases, (29%). There were a total of 19 events, 13 relapses, two secondary acute myeloid leukaemia and four toxic deaths (5%). The 5-year event-free survival (EFS) and overall survival (OS) was 78 +/- 4.5% and 85 +/- 3.9%, respectively. Relapsed patients had a 5-year OS of only 33 +/- 14%. Multivariate analysis failed to demonstrate age, gender, lactate dehydrogenase level, presence of marrow and/or central nervous system disease to have independent prognostic value. These results suggest that this experimental approach is safe and results in similar outcomes as more prolonged childhood ALL regimens.

  9. Triple Negative Breast Cancer Patients Treated at MD Anderson Cancer Center in Phase I Trials: Improved Outcomes with Combination Chemotherapy and Targeted Agents

    PubMed Central

    Ganesan, Prasanth; Moulder, Stacy; Lee, J. Jack; Janku, Filip; Valero, Vicente; Zinner, Ralph G.; Naing, Aung; Fu, Siqing; Tsimberidou, Apostolia M.; Hong, David; Stephen, Bettzy; Stephens, Philip; Yelensky, Roman; Meric-Bernstam, Funda; Kurzrock, Razelle; Wheler, Jennifer J.

    2014-01-01

    Patients with metastatic triple negative breast cancer (TNBC) have poor treatment outcomes. We reviewed the electronic records of consecutive patients with metastatic TNBC treated in phase I clinic at MD Anderson between August 2005 and May 2012. One hundred and six patients received at least 1 phase I trial. Twelve of 98 evaluable patients (12%) had either complete response (n=1); partial response (n=7); or, stable disease ≥6 months (n=4). Patients treated on matched therapy (n=16) compared to those on non-matched therapy (n=90) had improved SD≥6 months/PR/CR (33% vs 8%; p=0.018) and longer PFS (median, 6.4 vs 1.9 months; p=0.001). Eleven of 57 evaluable patients (19%) treated with combination chemotherapy and targeted therapy had SD≥ 6 months/PR/CR versus 1 of 41 evaluable patients (2%) treated on other phase I trials (p=0.013); and longer PFS (3.0 vs 1.6 months; p<0.0001). Patients with molecular alterations in the PI3K/AKT/mTOR pathway treated on matched therapy (n=16) had improved PFS compared to those with and without molecular alterations treated on non-matched therapy (n=27) (6.4 vs 3.2 months; p= 0.036). On multivariate analysis, improved PFS was associated with treatment with combined chemotherapy and targeted agents (p=0.0002); ≤2 metastatic sites (p=0.003); therapy with PI3K/AKT/mTOR inhibitors for those with cognate pathway abnormalities (p=0.018); and, treatment with anti-angiogenic agents (p=0.023). In summary, combinations of chemotherapy and angiogenesis and/or PI3K/AKT/mTOR inhibitors demonstrated improved outcomes in metastatic TNBC patients. PMID:25253784

  10. Feasibility of olanzapine, multi acting receptor targeted antipsychotic agent, for the prevention of emesis caused by continuous cisplatin- or ifosfamide-based chemotherapy.

    PubMed

    Bun, Seiko; Yonemori, Kan; Akagi, Toru; Noguchi, Emi; Shimoi, Tatsunori; Shimomura, Akihiko; Yunokawa, Mayu; Shimizu, Chikako; Fujiwara, Yasuhiro; Makino, Yoshinori; Hayashi, Yoshikazu; Tamura, Kenji

    2017-07-21

    Background To determine the feasibility and efficacy of olanzapine, which is approved by the Pharmaceuticals and Medical Devices Agency as multi acting receptor targeted antipsychotic agent of the thienobenzodiazepine class, for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients undergoing continuous five-day chemotherapy. Patients and methods This study was a prospective dose escalation study at a single center (UMIN ID: UMIN000015386). Patients received a combination of adriamycin and ifosfamide (AI) or a combination of bleomycin, etoposide, and cisplatin (BEP). On days 1-5, all patients received intravenous granisetron (1 mg) and intravenous dexamethasone sodium phosphate (24 mg). Olanzapine was administrated on day-1 to day5 at bedtime. The dose of olanzapine followed a dose-escalation scheme, with monitoring of safety and tolerability at each dose. A 3 + 3 cohort design was used, with three to six patients per cohort. Results Nine patients were enrolled (three for each cohort). No patients experienced dose-limiting toxicity (DLT). The most frequent adverse events were dry mouth and constipation. In each cohort, the maximum severity of nausea was Grade 2, and no patients experienced a vomiting episode. Conclusion A 2.5 mg/day dosage of olanzapine is sufficient to prevent from CINV in Japanese patients receiving continuous five-day chemotherapy. A dose of 10 mg/day, which is recommended by international CINV guidelines, is also tolerated. If CINV is not controlled by an initial dose of 2.5 mg/day of olanzapine, dosage escalation is encouraged. Future studies should compare olanzapine with aprepitant.

  11. Allogeneic hematopoietic stem cell transplantation for nonmalignant hematologic disorders using chemotherapy-only cytoreductive regimens and T-cell-depleted grafts from human leukocyte antigen-matched or -mismatched donors.

    PubMed

    Mussetti, Alberto; Kernan, Nancy A; Prockop, Susan E; Scaradavou, Andromachi; Lehrman, Rachel; Ruggiero, Julianne M; Curran, Kevin; Kobos, Rachel; O'Reilly, Richard; Boulad, Farid

    2016-09-01

    Nonmalignant hematologic disorders (NMHD) of childhood comprise a variety of disorders, including acquired severe aplastic anemia and inherited marrow failure syndromes. Patients with high-risk NMHD without matched related donors fare poorly with allogeneic hematopoietic alternative donor stem cell transplantation (allo-HSCT) and are at high risk for developing graft-versus-host disease following unmodified grafts. The authors retrospectively analyzed data on 18 patients affected by NMHD, lacking a human leukocyte antigen (HLA)-identical sibling donor, who underwent an alternative donor allo-HSCT at their institution between April 2005 and May 2013. Fifty percent of the patients had received prior immunosuppressive therapy, 72% had a history of infections, and 56% were transfusion dependent at the time of transplant. Cytoreduction included a combination of 3 of 5 agents: fludarabine, melphalan, thiotepa, busulfan, and cyclophosphamide. Grafts were T-cell depleted. All evaluable patients engrafted. Five died of transplant complications. The cumulative incidence of graft-versus-host disease was 6%. No patient had recurrence of disease. Five-year overall survival was 77%. Age at transplant <6 years was strongly associated with better survival. Based on these results, transplant with chemotherapy-only cytoreductive regimens and T-cell-depleted stem cell transplants could be recommended for patients with high-risk NMHD, especially at a younger age.

  12. The Efficacy of Combining Antiangiogenic Agents with Chemotherapy for Patients with Advanced Non-Small Cell Lung Cancer Who Failed First-Line Chemotherapy: A Systematic Review and Meta-Analysis

    PubMed Central

    Yang, Bijun; Zhang, Yaxiong; Kang, Shiyang; Zhou, Ting; Hong, Shaodong; Qin, Tao; Hu, Zhihuang; Fang, Wenfeng; Huang, Yan; Zhang, Li

    2015-01-01

    Background The clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients. Methods We conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients. Results Thirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02). Conclusions This study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy. PMID:26034985

  13. The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents.

    PubMed

    Mhaskar, Rahul; Wao, Hesborn; Miladinovic, Branko; Kumar, Ambuj; Djulbegovic, Benjamin

    2016-02-04

    Erythropoiesis-stimulating agents (ESAs) are commonly used to treat chemotherapy-induced anemia (CIA). However, about half of patients do not benefit. To evaluate the benefits and harms related to the use of iron as a supplement to ESA and iron alone compared with ESA alone in the management of CIA. We searched for relevant trials from the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1 January 2016), MEDLINE (1950 to February 2016), and www.clinicaltrials.gov without using any language limits. All randomized controlled trials (RCTs) comparing 'iron plus ESA' or 'iron alone' versus 'ESA alone' in people with CIA were eligible for inclusion. We used standard methodological procedures expected by Cochrane. We included eight RCTs (12 comparisons) comparing ESA plus iron versus ESA alone enrolling 2087 participants. We did not find any trial comparing iron alone versus ESAs alone in people with CIA. None of the included RCTs reported overall survival. There was a beneficial effect of iron supplementation to ESAs compared with ESAs alone on hematopoietic response (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.09 to 1.26; P < 0.0001; 1712 participants; 11 comparisons; high-quality evidence). Assuming a baseline risk of 35% to 80% for hematopoietic response without iron supplementation, between seven and 16 patients should be treated to achieve hematopoietic response in one patient. In subgroup analyses, RCTs that used intravenous (IV) iron favored ESAs and iron (RR 1.20 (95% CI 1.10 to 1.31); P < 0.00001; 1321 participants; eight comparisons), whereas we found no evidence for a difference in hematopoietic response in RCTs using oral iron (RR 1.04 (95% CI 0.87 to 1.24); P = 0.68; 391 participants; three comparisons). There was no evidence for a difference between the subgroups of IV and oral iron (P = 0.16). There was no evidence for a difference between the subgroups of types of iron (P = 0.31) and types of ESAs (P = 0.16) for hematopoietic

  14. Managing Metastatic Castration-Resistant Prostate Cancer in the Pre-chemotherapy Setting: A Changing Approach in the Era of New Targeted Agents.

    PubMed

    Zafeiriou, Zafeiris; Jayaram, Anuradha; Sharp, Adam; de Bono, Johann S

    2016-03-01

    In recent years, the therapeutic options for treating men with metastatic castration-resistant prostate cancer have increased substantially. The hormonal treatments abiraterone acetate and enzalutamide, the chemotherapeutics docetaxel and cabazitaxel, the radiopharmaceutical alpharadin and the immunotherapeutic Sipuleucel-T have entered the field. Additionally, corticosteroids, which are used extensively, have documented activity but no documented survival benefit. Physicians treating patients with metastatic prostate cancer immediately after castration resistance develops currently have at least four different options to choose from for the first treatment. These therapeutic choices and their several possible ways of sequential use have not yet been compared to each other head-to-head and may never be. Therefore, there is an unmet need to inform their use with prospective clinical data. Additionally, the new indications of docetaxel for hormone naïve prostate cancer is changing the landscape of prostate cancer treatment and questions the traditional classifications 'pre-chemotherapy' and 'post-chemotherapy'. In this work we attempt to address these challenges in the treatment of metastatic castration-resistant prostate cancer with the focus mainly on the non-cytotoxic agents. We try to integrate available clinical and preclinical information to suggest optimal ways of treatment.

  15. Propensity score matched assessment of treatment patterns and cost of erythropoiesis stimulating agent treatment in patients with cancer receiving myelosuppressive chemotherapy.

    PubMed

    Tunceli, Ozgur; Bailey, Robert A; Stephenson, Judith J; Singer, Joseph

    2013-12-01

    To examine epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment patterns and erythropoiesis stimulating agent (ESA) costs in patients with cancer receiving chemotherapy (CRC), and to compare the results observed in the pre-matched total study population (TSP) with a propensity score matched population (PSMP). A medical claims analysis was conducted from 1 January 2004 through 31 July 2009 using the HealthCore Integrated Research Database. Patients were at least 18 years old, newly initiated on EPO or DARB, received ≥ 2 ESA doses, and had ≥ 1 claim for cancer and chemotherapy proximate to ESA treatment. Patients were matched using propensity scores. January 2010 Wholesale Acquisition Cost was used to calculate drug cost. Mean cumulative ESA dose and drug costs were evaluated in the TSP and PSMP. 4921 EPO and 9173 DARB patients with CRC were identified. In the TSP, mean cumulative ESA doses were EPO: 398,770 units and DARB: 1508 mcg, with similar treatment durations for each. Mean cumulative drug costs were EPO: $6041 and DARB: $7861 (30% higher for DARB). The cumulative dose ratio (EPO units: DARB mcg) was 264:1. The PSMP analysis identified 4831 ESA treated CRC patients in each group. Mean drug costs were EPO: $6055 and DARB: $7863 (30% higher for DARB). The observed dose ratio (EPO units: DARB mcg) was 265:1. In both analyses, the costs of DARB were higher, even after accounting for baseline differences in the PSMP. Similar trends in dose ratios were also observed in both groups.

  16. Chemotherapy, targeted agents, antiemetics and growth-factors in human milk: how should we counsel cancer patients about breastfeeding?

    PubMed

    Pistilli, Barbara; Bellettini, Giulia; Giovannetti, Elisa; Codacci-Pisanelli, Giovanni; Azim, Hatem A; Benedetti, Giovanni; Sarno, Maria Anna; Peccatori, Fedro A

    2013-05-01

    An increasing number of women are diagnosed with cancer during pregnancy and lactation. Women are usually advised to interrupt breastfeeding during systemic anticancer treatment for fear of serious adverse effects to the nursed infant. However, the issue is poorly addressed in the literature and very few studies have evaluated the safety of breastfeeding during or after cytotoxic drugs or target agents administration. In this review we will analyze the available evidence that addresses the issue of anticancer drugs, targeted agents, antiemetics and growth-factors excretion in human milk. This could serve as a unique resource that may aid physicians in the management of breastfeeding cancer patients interested in maintaining lactation during treatment.

  17. Chemotherapy-induced alopecia.

    PubMed

    Trüeb, Ralph M

    2010-12-01

    Few dermatologic conditions carry as much emotional distress as chemotherapy-induced hair loss. Forty-seven percent of female patients consider hair loss the most traumatic aspect of chemotherapy, and 8% would decline chemotherapy because of fear of hair loss. A number of agents have been evaluated on the basis of the current understanding of the underlying pathobiology. Among the agents that have been evaluated, topical minoxidil was able to reduce the severity or shorten the duration but could not prevent hair loss. The major approach to minimize chemotherapy-induced hair loss is by scalp cooling, although most published data on scalp cooling are of poor quality. Because chemotherapy-induced toxicity has been associated with nutritional status, nutritional assessment and support might confer beneficial effects. Several experimental approaches to the development of pharmacological agents are under evaluation including: anti-oxidants, cytokines and growth factors, cell cycle and proliferation modifiers, and inhibitors of apoptosis. At present, no approved pharmacologic treatment of chemotherapy-induced hair loss exists. The incidence and severity of the condition are variable and related to the particular chemotherapeutic protocol. Fortunately, chemotherapy-induced hair loss is mostly reversible, and appropriate hair and scalp care and temporarily wearing a wig may be the most effective coping strategy.

  18. Innovative Treatments for Cancer:. The Impact of Delivering siRNAs, Chemotherapies, and Preventative Agents Using Nanoformulations

    NASA Astrophysics Data System (ADS)

    Hook, Sara S.; Farrell, Dorothy; Hinkal, George W.; Ptak, Krzystzof; Grodzinski, Piotr; Panaro, Nicholas J.

    2013-09-01

    A multi-disciplinary approach to research epitomized by the emerging field of cancer nanotechnology can catalyze scientific developments and enable clinical translation beyond what we currently utilize. Engineers, chemists, and physical scientists are teaming up with cancer biologists and clinical oncologists to attack the vast array of cancer malignancies using materials at the nanoscale. We discuss how nanoformulations are enabling the targeted, efficient, delivery of not only genetic therapies such silencing RNAs, but also conventional cytotoxic agents and small molecules which results in decreased systemic toxicity and improved therapeutic index. As preventative approaches, there are various imaging agents and devices are being developed for screening purposes as well as new formulations of sunscreens, neutraceuticals, and cancer vaccines. The goal then of incorporating nanotechnology into clinical applications is to achieve new and more effective ways of diagnosing, treating, and preventing cancer to ultimately change the lives of patients worldwide.

  19. Chemotherapy-Related Neurotoxicity.

    PubMed

    Taillibert, Sophie; Le Rhun, Emilie; Chamberlain, Marc C

    2016-09-01

    Chemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer.

  20. A study of the susceptibility of different mice strains to thio-TEPA: An experiment with recombinant strains

    SciTech Connect

    Malashenko, A.M.; Beskova, T.B.

    1995-07-01

    The study is devoted to the clastogenic effect of thio-TEPA in raising recombinant strains 1XC3 in mice (obtained from 101/H x C3H/Sn crossing). By the summer of 1993, 15 strains had reached 10 generations of inbreeding. Five to six sibs of each strain (males and females) aged 6-8 weeks were treated with the mutagen (3 mg/kg, i/p). Strain sensitivity was estimated by the frequency of marrow cells exhibiting chromosome lesions (including gaps). According to this characteristic, the strains were divided into two unequal groups. The first one included 12 less-sensitive strains (chromosome aberrations were present, on average, in 33.5% of the cells, and lay in the range from 27.0{+-}4.5 to 39.8{+-}4.9). The second group included three more-sensitive strains with 51.2, 51.7, and 59.5% of the cells being affected (54.1% on average). A similar difference between the groups was found with respect to the number of breaks per cell: 1.15 in resistant strains and 2.88 in sensitive ones. This difference was significant and similar to that found earlier for C3H and 101 strains. Thus, the results obtained support the hypothesis that mice of the 101/H strain carry a gene enhancing sensitivity to chemical mutagens (mut-l). Some strains of the first group were eliminated; the remaining ones will be bred until the 20th generation, when they will be investigated again in more detail. 24 refs., 1 fig., 2 tabs.

  1. Alkylating agents and immunotoxins exert synergistic cytotoxic activity against ovarian cancer cells. Mechanism of action.

    PubMed Central

    Lidor, Y J; O'Briant, K C; Xu, F J; Hamilton, T C; Ozols, R F; Bast, R C

    1993-01-01

    Alkylating agents can be administered in high dosage to patients with ovarian cancer using autologous bone marrow support, but drug-resistant tumor cells can still persist. Immunotoxins provide reagents that might eliminate drug resistant cells. In the present study, concurrent treatment with alkylators and immunotoxins proved superior to treatment with each agent alone. Toxin immunoconjugates prepared from different monoclonal antibodies and recombinant ricin A chain (rRTA) inhibited clonogenic growth of ovarian cancer cell lines in limiting dilution assays. When alkylating agents and toxin conjugates were used in combination, the addition of the immunotoxins to cisplatin, or to cisplatin and thiotepa, produced synergistic cytotoxic activity against the OVCA 432 and OVCAR III cell lines. Studies performed to clarify the mechanism of action showed that cisplatin and thiotepa had no influence on internalization and binding of the 317G5-rRTA immunotoxin. Intracellular uptake of [195m]Pt-cisplatin was not affected by the immunoconjugate and thiotepa. The combination of the 317G5-rRTA and thiotepa, as well as 317G5-rRTA alone, increased [195m]Pt cisplatin-DNA adduct levels. The immunotoxin alone and in combination with the alkylators decreased intracellular glutathione levels and reduced glutathione-S-transferase activity. Repair of DNA damage induced by the combination of alkylators and 317G5-rRTA was significantly reduced when compared to repair after damage with alkylators alone. These findings suggest that immunotoxins affect levels and activity of enzymes required for the prevention and repair of alkylator damage. Images PMID:8227359

  2. [Correlation of changes in bone marrow cell sensitivity to the clastogenic effect of thiotepa and fertility in CBA/LacY mice in successive inbred generations].

    PubMed

    Malashenko, A M; Ignat'eva, E L; Beskova, T B

    1997-12-01

    The causes of the significant increases in the sensitivity to of clastogenic effect of thio-TEPA in bone marrow cells of inbred CBA/LacY mice were studied. The increases were shown to be associated with decreased fertility. The fluctuations of fertility and the association of fertility and sensitivity with thio-TEPA were analyzed in foundation stocks (FSs) for 24 and 6 inbred generations, respectively. The stocks examined were obtained in the Laboratory of Experimental Biological Models and the Stolbovaya breeding facility. The correlation analysis revealed a significant association of fluctuations of the coefficient of fertility in two FSs (eta = 0.78 +/- 0.13) and a high negative correlation between fertility and mutagen sensitivity in inbred generations (r = -0.91 +/- 0.21). The comparison between the fluctuations of fertility for four generations revealed the same fluctuation period in CBA/LacY, DBA/2Y, and C57Bl/6JY mice. The detected phenomena were assumed to result from genetically determined regular fluctuations in genome functioning. This explained a number of observations and allowed several prognoses to be made.

  3. Single-agent DTIC versus combination chemotherapy with or without immunotherapy in metastatic melanoma: a meta-analysis of 3273 patients from 20 randomized trials.

    PubMed

    Huncharek, M; Caubet, J F; McGarry, R

    2001-02-01

    It is currently unclear whether any combination therapy for the treatment of metastatic melanoma is superior to standard single-agent dacarbazine (DTIC) in terms of tumour response and overall survival. The available randomized clinical trial data were combined in a meta-analysis to address this question. Initially a thorough MEDLARS search was conducted covering the time period from January 1970 to January 1999. This literature search was supplemented by manual searches of study bibliographies (including review articles) and review of relevant textbooks. The meta-analysis was performed according to a prospective protocol using strict study eligibility criteria. Data derived from randomized controlled trials comparing single-agent DTIC with combination chemo/immunotherapy were combined using a fixed effects model. Data were stratified into three combination therapy groups: DTIC-containing regimens, non-DTIC-containing therapy, and chemotherapy plus immunotherapy. The primary outcome of interest was the proportion of patients demonstrating a complete or partial response to treatment. A total of 20 randomized trials comprising 3273 patients were initially combined in a meta-analysis. This yielded an odds ratio (OR) of 1.23 (95% confidence interval [CI] 1.02-1.48), demonstrating that combination drug therapies are associated with a 23% increase in response rate compared with single-agent DTIC. The combination of DTIC plus interferon-alpha produced a tumour response rate 53% greater (95% CI 1.10-2.13) than that seen with DTIC alone. This increase was greater than that seen with DTIC-containing multi-drug regimens, which had an OR of 1.33 (95% CI 0.99-1.78). No difference in overall survival was demonstrated. Non-DTIC-containing treatment programmes showed no advantage over DTIC in terms of tumour response rate (OR = 0.77, 95% CI 0.45-1.32). The combination of DTIC and interferon-alpha appears more active than standard single-agent DTIC in metastatic melanoma. Further

  4. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, with irinotecan hydrochloride on human colorectal and gastric cancer xenografts.

    PubMed

    Nukatsuka, Mamoru; Nakagawa, Fumio; Saito, Hitoshi; Sakata, Minoru; Uchida, Junji; Takechi, Teiji

    2015-03-01

    TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine and tipiracil hydrochloride at a molar ratio of 1:0.5. TAS-102 was approved in Japan in March 2014 for the treatment of patients with unresectable, advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, enhancement of the therapeutic efficacy using a combination therapy of TAS-102 and irinotecan hydrochloride (CPT-11) was evaluated in a colorectal and gastric cancer xenograft-bearing nude mouse model. TAS-102 was orally administered twice a day from day 1 to 14, and CPT-11 was administered intravenously on days 1 and 8. The growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, which was estimated based on the period required to reach a tumor volume that was five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and the RTV5 of the group receiving TAS-102 with CPT-11 were significantly superior to those of both agents as monotherapy for mice with KM12C, KM12C/5-FU, DLD-1/5-FU, and SC-2 xenografts (p<0.01). No significant decrease in body weight was observed. The present pre-clinical findings indicated that the combination of TAS-102 and CPT-11 is a promising treatment option for colorectal or gastric cancer, not only for chemo-naïve tumors, but also for recurrent tumors after 5-fluorouracil (5-FU)-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. An AS1411 aptamer-conjugated liposomal system containing a bubble-generating agent for tumor-specific chemotherapy that overcomes multidrug resistance.

    PubMed

    Liao, Zi-Xian; Chuang, Er-Yuan; Lin, Chia-Chen; Ho, Yi-Cheng; Lin, Kun-Ju; Cheng, Po-Yuan; Chen, Ko-Jie; Wei, Hao-Ji; Sung, Hsing-Wen

    2015-06-28

    Recent research in chemotherapy has prioritized overcoming the multidrug resistance (MDR) of cancer cells. In this work, liposomes that contain doxorubicin (DOX) and ammonium bicarbonate (ABC, a bubble-generating agent) are prepared and functionalized with an antinucleolin aptamer (AS1411 liposomes) to target DOX-resistant breast cancer cells (MCF-7/ADR), which overexpress nucleolin receptors. Free DOX and liposomes without functionalization with AS1411 (plain liposomes) were used as controls. The results of molecular dynamic simulations suggest that AS1411 functionalization may promote the affinity and specific binding of liposomes to the nucleolin receptors, enhancing their subsequent uptake by tumor cells, whereas plain liposomes enter cells with difficulty. Upon mild heating, the decomposition of ABC that is encapsulated in the liposomes enables the immediate activation of generation of CO2 bubbles, creating permeable defects in their lipid bilayers, and ultimately facilitating the swift intracellular release of DOX. In vivo studies in nude mice that bear tumors demonstrate that the active targeting of AS1411 liposomes can substantially increase the accumulation of DOX in the tumor tissues relative to free DOX or passively targeted plain liposomes, inhibiting tumor growth and reducing systemic side effects, including cardiotoxicity. The above findings indicate that liposomes that are functionalized with AS1411 represent an attractive therapeutic alternative for overcoming the MDR effect, and support a potentially effective strategy for cancer therapy.

  6. Phase II study of single-agent bosutinib, a Src/Abl tyrosine kinase inhibitor, in patients with locally advanced or metastatic breast cancer pretreated with chemotherapy.

    PubMed

    Campone, M; Bondarenko, I; Brincat, S; Hotko, Y; Munster, P N; Chmielowska, E; Fumoleau, P; Ward, R; Bardy-Bouxin, N; Leip, E; Turnbull, K; Zacharchuk, C; Epstein, R J

    2012-03-01

    This phase II study evaluated single-agent bosutinib in pretreated patients with locally advanced or metastatic breast cancer. Patients received oral bosutinib 400 mg/day. The primary end point was the progression-free survival (PFS) rate at 16 weeks. Secondary end points included objective response rate, clinical benefit rate, 2-year overall survival rate, safety, and changes in levels of bone resorption/formation biomarkers. Seventy-three patients were enrolled and treated. Median time from diagnosis of metastatic disease to initiation of bosutinib treatment was 24.5 months. For the intent-to-treat population, the PFS rate at 16 weeks was 39.6%. Unexpectedly, all responding patients (n = 4) were hormone receptor positive. The clinical benefit rate was 27.4%. The 2-year overall survival rate was 26.4%. The main toxic effects were diarrhea (66%), nausea (55%), and vomiting (47%). Grade 3-4 laboratory aminotransferase elevations occurred in 14 (19%) patients. Myelosuppression was minimal. No consistent changes in the levels of bone resorption/formation biomarkers were seen. Bosutinib showed promising efficacy in prolonging time to progression in chemotherapy-pretreated patients with locally advanced or metastatic breast cancer. Bosutinib was generally well tolerated, with a safety profile different from that of the Src/Abl tyrosine kinase inhibitor dasatinib in a similar patient population.

  7. Secondary malignancies following cancer chemotherapy.

    PubMed

    Boffetta, P; Kaldor, J M

    1994-01-01

    Many agents used in cancer chemotherapy are known carcinogens. However, few secondary malignancies have been definitely linked to chemotherapy, since studies on this problem are complicated by methodological problems. A causal relationship has been established between alkylating agents and leukaemia and between cyclophosphamide and bladder cancer. The risk of leukaemia peaks at 5-10 years after beginning of chemotherapy and declines steadily after its end. The interaction between chemotherapy and radiotherapy has not been fully clarified, nor has the leukaemogenic potency of individual drugs, although combinations without nitrogen mustard seem to entail a lower risk. Other tumours reported at increased incidence, in particular among Hodgkin's disease patients, for whom a carcinogenic effect of chemotherapy seems plausible, are non-Hodgkin's lymphoma and lung cancer. Other secondary solid tumors have also been reported, but for none of them an independent effect of chemotherapy has been demonstrated.

  8. FePt nanoparticles as a potential X-ray activated chemotherapy agent for HeLa cells

    PubMed Central

    Zheng, Yanhong; Tang, Yunlan; Bao, Zhirong; Wang, Hui; Ren, Feng; Guo, Mingxiong; Quan, Hong; Jiang, Changzhong

    2015-01-01

    Nanomaterials have an advantage in “personalized” therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration <250 μg/mL. Meanwhile, the FePt NPs showed negative/positive contrast enhancement for MRI/CT molecule imaging at the end of the study. Therefore, the combined results implied that FePt NPs might potentially serve as a promising nanoprobe for the integration of tumor diagnosis and chemoradiotherapy. PMID:26604740

  9. FePt nanoparticles as a potential X-ray activated chemotherapy agent for HeLa cells.

    PubMed

    Zheng, Yanhong; Tang, Yunlan; Bao, Zhirong; Wang, Hui; Ren, Feng; Guo, Mingxiong; Quan, Hong; Jiang, Changzhong

    2015-01-01

    Nanomaterials have an advantage in "personalized" therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration <250 μg/mL. Meanwhile, the FePt NPs showed negative/positive contrast enhancement for MRI/CT molecule imaging at the end of the study. Therefore, the combined results implied that FePt NPs might potentially serve as a promising nanoprobe for the integration of tumor diagnosis and chemoradiotherapy.

  10. Cancer Chemotherapy

    MedlinePlus

    ... controlled way. Cancer cells keep growing without control. Chemotherapy is drug therapy for cancer. It works by killing the cancer ... It depends on the type and amount of chemotherapy you get and how your body reacts. Some ...

  11. STUDIES ON CHEMOTHERAPY AND SERODIAGNOSIS FOR CLONORCHIS SINENSIS INFECTION.

    DTIC Science & Technology

    CHEMOTHERAPEUTIC AGENTS, *SERODIAGNOSIS, PARASITIC DISEASES , CHEMOTHERAPY, PARASITIC DISEASES , DOSAGE, TOXICITY, BODY WEIGHT, PATHOLOGY, MORTALITY RATE, HEMATOLOGY, SODIUM COMPOUNDS, BIOASSAY, JAPAN.

  12. Chemotherapy and signaling

    PubMed Central

    Bagnyukova, Tetyana; Serebriiskii, Ilya G; Zhou, Yan; Hopper-Borge, Elizabeth A; Golemis, Erica A

    2010-01-01

    In recent years, oncologists have begun to conclude that chemotherapy has reached a plateau of efficacy as a primary treatment modality, even if toxicity can be effectively controlled. Emerging specific inhibitors of signaling and metabolic pathways (i.e., targeted agents) contrast with traditional chemotherapy drugs in that the latter primarily interfere with the DNA biosynthesis and the cell replication machinery. In an attempt to improve on the efficacy, combination of targeted drugs with conventional chemotherapeutics has become a routine way of testing multiple new agents in early phase clinical trials. This review discusses the recent advances including integrative systematic biology and RNAi approaches to counteract the chemotherapy resistance and to buttress the selectivity, efficacy and personalization of anticancer drug therapy. PMID:20935499

  13. Agents.

    PubMed

    Chambers, David W

    2002-01-01

    Although health care is inherently an economic activity, it is inadequately described as a market process. An alternative, grounded in organizational economic theory, is to view professionals and many others as agents, contracted to advance the best interests of their principals (patients). This view untangles some of the ethical conflicts in dentistry. It also helps identify major controllable costs in dentistry and suggests that dentists can act as a group to increase or decrease agency costs, primarily by controlling the bad actors who damage the value of all dentists.

  14. Thiotepa-based versus total body irradiation-based myeloablative conditioning prior to allogeneic stem cell transplantation for acute myeloid leukaemia in first complete remission: a retrospective analysis from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Eder, Sandra; Labopin, Myriam; Arcese, William; Or, Reuven; Majolino, Ignazio; Bacigalupo, Andrea; de Rosa, Gennaro; Volin, Liisa; Beelen, Dietrich; Veelken, Hendrik; Schaap, Nicolaas P M; Kuball, Jurgen; Cornelissen, Jan; Nagler, Arnon; Mohty, Mohamad

    2016-01-01

    Thiotepa is an alkylating compound with an antineoplastic and myeloablative activity and can mimic the effect of radiation. However, it is unknown whether this new regimen could safely replace the long-established ones. This retrospective matched-pair analysis evaluated the outcome of adults with acute myeloid leukaemia in first complete remission who received myeloablative conditioning either with a thiotepa-based (n = 121) or a cyclophosphamide/total body irradiation-based (TBI; n = 358) regimen for allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling or an unrelated donor. With a median follow-up of 44 months, the outcome was similar in both groups. Acute graft-versus-host disease grade II-IV was observed in 25% after thiotepa-containing regimen versus 35% after TBI (P = 0.06). The 2-yr cumulative incidence of chronic graft-versus-host disease was 40.5% for thiotepa and 41% for TBI (P = 0.98). At 2 yrs, the cumulative incidences of non-relapse mortality and relapse incidence were 23.9% (thiotepa) vs. 22.4% (TBI; P = 0.66) and 17.2% (thiotepa) vs. 23.3% (TBI; P = 0.77), respectively. The probabilities of leukaemia-free and overall survival at 2 yrs were not significantly different between the thiotepa and TBI groups, at 58.9% vs. 54.2% (P = 0.95) and 61.4% vs. 58% (P = 0.72), respectively. Myeloablative regimens using combinations including thiotepa can provide satisfactory outcomes, but the optimal conditioning remains unclear for the individual patient in this setting. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Chemotherapy Effects

    MedlinePlus

    ... Falling Fatigue Fertility and Sexual Side Effects Fever Hair ... Cancers Caused by Cancer Treatment Some cancer treatments such as chemotherapy and radiation therapy may increase a person's risk ...

  16. Pilot Study of Intensive Chemotherapy with Peripheral Hematopoietic Cell Support for Children Less than 3 Years of Age with Malignant Brain Tumors, The CCG-99703 Phase I/II Study. A Report from the Children’s Oncology Group

    PubMed Central

    Cohen, Bruce H.; Geyer, J. Russell; Miller, Douglas C.; Curran, John G.; Zhou, Tianni; Holmes, Emi; Ingles, Sue Ann; Dunkel, Ira J.; Hilden, Joanne; Packer, Roger J.; Pollack, Ian F.; Gajjar, Amar; Finlay, Jonathan L.

    2016-01-01

    Background The primary goals of the CCG-99703 study were to assess the feasibility and tolerability of, as well as the response rate to, a novel dose-intensive chemotherapy regimen. Methods Between March 1998 and October 2004, 92 eligible patients were enrolled. Following biopsy/resection, patients received three identical cycles of Induction chemotherapy (vincristine, cyclophosphamide, etoposide and cisplatin) administered every 21–28 days. Patients without tumor progression then received three Consolidation cycles of marrow-ablative chemotherapy (thiotepa and carboplatin) followed by autologous hematopoietic cell rescue. Results The Maximum Tolerated Dose (MTD) of thiotepa was 10mg/kg/day x 2 days per cycle. The toxic mortality rate was zero during Induction and 2.6% during Consolidation. Centrally evaluated response rates to Induction and Consolidation in evaluable patients with residual tumor were 73.3% and 66.7% respectively. Disease progression rates on Induction and Consolidation were 4%. Five-year EFS and OS were 43.9±5.2% and 63.6±5% respectively. Gross total resection (GTR) versus thiotepa regimen determined an MTD that had acceptable toxicity. Overall survival data justify this strategy for current COG studies. PMID:26092413

  17. [Chemotherapy in Patients Complicated with Interstitial Pneumonia].

    PubMed

    Sata, Masafumi; Kato, Terufumi

    2016-08-01

    Interstitial pneumonia has high risk for chemotherapy-related exacerbation. Chemotherapy-related exacerbation is often fatal with respiratory failure. When we treat the cancer patient with interstitial pneumonia, it is necessary for us to regard of the efficacy of chemotherapy, and the frequency and mortality of chemotherapy-related exacerbation. All anti-cancer drugs has the possibilities of chemotherapy-related exacerbation. The incidence of chemotherapy-related exacerbation was higher in patients with target therapy agent or immune-checkpoint therapy agent, though there is not an interstitial pneumonia patient. In patients complicated with interstitial pneumonia, you should not use of these drugs, such as target therapy agent or immune-checkpoint therapy agent.

  18. Feasibility of adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 for completely resected non-small-cell lung cancer: results of the Setouchi Lung Cancer Group Study 1001.

    PubMed

    Okumura, Norihito; Sonobe, Makoto; Okabe, Kazunori; Nakamura, Hiroshige; Kataoka, Masafumi; Yamashita, Motohiro; Nakata, Masao; Kataoka, Kazuhiko; Yamashita, Yoshinori; Soh, Junichi; Yoshioka, Hiroshige; Hotta, Katsuyuki; Matsuo, Keitaro; Sakamoto, Junichi; Toyooka, Shinichi; Date, Hiroshi

    2017-04-01

    This multicenter study evaluated the feasibility of novel adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent, long-term maintenance with S-1 in patients with completely resected stage II-IIIA non-small-cell lung cancer (NSCLC). Patients received four cycles of S-1 (80 mg/m(2)/day for 2 weeks, followed by 2 weeks rest) plus carboplatin (area under the curve 5, day 1) followed by S-1 (80 mg/m(2)/day for 2 weeks, followed by a 1-week rest). Patients unable to continue S-1 plus carboplatin because of severe toxicity converted to single-agent S-1 maintenance. The duration of adjuvant chemotherapy was 10 months in both situations. The primary endpoint was feasibility, defined as the proportion of patients who completed four cycles of S-1 plus carboplatin and single-agent S-1 maintenance for 10 months. The treatment completion rate was determined; treatment was considered feasible if the lower 90% confidence interval (CI) was ≥50%. Eighty-nine patients were enrolled, of whom 87 were eligible and assessable. Seventy-eight patients (89.7%) completed four cycles of S-1 plus carboplatin and 55 (63.2%) completed the following S-1 maintenance therapy for a total of 10 months. The treatment completion rate was 63.2% (90% CI, 54.4-71.2%), indicating feasibility. There were no treatment-related deaths. Grade 3/4 toxicities included neutropenia (13.8%), thrombocytopenia (11.5%), and anorexia (4.6%). The 2-year relapse-free survival rate was 59.8%. We concluded that adjuvant chemotherapy with S-1 plus carboplatin followed by single-agent maintenance therapy with S-1 is feasible and tolerable in patients with completely resected NSCLC. UMIN000005041.

  19. Maintenance single-agent bevacizumab or observation after first-line chemotherapy in patients with metastatic colorectal cancer: a multicenter retrospective study.

    PubMed

    Moscetti, Luca; Nelli, Fabrizio; Fabbri, Maria A; Sperduti, Isabella; Alesini, Daniele; Cortesi, Enrico; Gemma, Donatello; Gamucci, Teresa; Grande, Roberta; Pavese, Ida; Franco, Daniela; Ruggeri, Enzo M

    2013-08-01

    The addition of bevacizumab to standard chemotherapy has improved progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) in both first- and second line treatment, but the role of maintenance bevacizumab remains controversial. The association of various clinical factor and survival was examined in this retrospective cohort analysis. The clinical data from 220 previously untreated patients with mCRC, not progressive at the end of standard chemotherapy plus bevacizumab, were collected and analyzed. Patients were classified into two subgroups: those given with maintenance bevacizumab: "maintenance bevacizumab cohort (n = 118; MB)", and those discontinuing bevacizumab as a result of physician's or patient's decision: "no maintenance bevacizumab cohort (n = 102; noMB)". The baseline factors were well balanced between the study subgroups. Median PFS and OS for the general population was 10 months (range 7-15) and 22.5 months (range 18-26), respectively. Median PFS was 13 and 8 months in the BM and noBM cohorts, respectively (p < 0.0001). In the multivariate analysis, maintenance therapy resulted independently associated with improved PFS (HR 1.73; p < 0.001), but only objective response (OR) after first-line chemotherapy was associated with improved OS. Maintenance chemotherapy cannot be considered a standard of care after induction chemotherapy for mCRC, because the optimal balance between efficacy and safety of maintenance therapy remains a significant challenge. The results of our retrospective study suggest that maintenance therapy with bevacizumab is a safe and valuable option, particularly in those patients achieving an objective response after first-line chemotherapy.

  20. Sex-specific effects of cytotoxic chemotherapy agents cyclophospha-mide and mitomycin C on gene expression, oxidative DNA damage, and epigenetic alterations in the prefrontal cortex and hippocampus – an aging connection

    PubMed Central

    Kovalchuk, Anna; Rodriguez-Juarez, Rocio; Ilnytskyy, Yaroslav; Byeon, Boseon; Shpyleva, Svitlana; Melnyk, Stepan; Pogribny, Igor; Kolb, Bryan; Kovalchuk, Olga

    2016-01-01

    Recent research shows that chemotherapy agents can be more toxic to healthy brain cells than to the target cancer cells. They cause a range of side effects, including memory loss and cognitive dysfunction that can persist long after the completion of treatment. This condition is known as chemo brain. The molecular and cellular mechanisms of chemo brain remain obscure. Here, we analyzed the effects of two cytotoxic chemotherapy drugs—cyclophosphamide (CPP) and mitomycin C (MMC) - on transcriptomic and epigenetic changes in the murine prefrontal cortex (PFC) and hippocampal regions. We for the first time showed that CPP and MMC treatments led to profound sex- and brain region-specific alterations in gene expression profiles. Gene expression changes were most prominent in the PFC tissues of female mice 3 weeks after MMC treatment, and the gene expression response was much greater for MCC than CPP exposure. MMC exposure resulted in oxidative DNA damage, evidenced by accumulation of 8-oxo-2′-deoxyguanosine (8-oxodG) and a decrease in the level of 8-oxodG repair protein OGG1 in the PFC of female animals 3 weeks after treatment. MMC treatment decreased global DNA methylation and increased DNA hydroxymethylation in the PFC tissues of female mice. The majority of the changes induced by chemotherapy in the PFC tissues of female mice resembled those that occur during the brain's aging processes. Therefore, our study suggests a link between chemotherapy-induced chemo brain and brain aging, and provides an important roadmap for future analysis. PMID:27032448

  1. Non-platinum doublets were as effective as platinum-based doublets for chemotherapy-naïve advanced non-small-cell lung cancer in the era of third-generation agents.

    PubMed

    Jiang, Jingwei; Liang, Xiaohua; Zhou, Xinli; Huang, Ruofan; Chu, Zhaohui; Zhan, Qiong

    2013-01-01

    The aim was to compare the efficacy between doublets of third-generation agents (non-platinum) and doublets of platinum plus a third-generation agent (platinum-based) for chemotherapy-naïve advanced non-small-cell lung cancer (NSCLC). We conducted a literature-based meta-analysis to compare the efficacy between doublets of third-generation agents and doublets of platinum plus a third-generation agent for chemotherapy-naïve advanced NSCLC. The primary end point was overall survival, and the secondary end points were progression-free survival (PFS) and response rate. Subgroup analyses were also conducted by different non-platinum doublet regimens or different platinum-based doublets. A descriptive review for toxicity was performed. Sixteen randomized controlled trials were identified ultimately. Results demonstrated that the efficacy of non-platinum doublets was comparable with platinum-based doublets according to the overall survival (HR = 1.03, 95 % CI = 0.98-1.08, p = 0.29). Subgroup analyses by different non-platinum doublets also showed the efficacy of all the third-generation doublets, such as vinorelbine plus gemcitabine, vinorelbine plus paclitaxel, gemcitabine plus paclitaxel, and gemcitabine plus docetaxel, was comparable with platinum-based doublets (HR = 1.00, 95 % CI = 0.78-1.27, p = 0.98; HR = 0.97, 95 % CI = 0.80-1.18, p = 0.79; HR = 1.05, 95 % CI = 0.99-1.12, p = 0.11; HR = 1.01, 95 % CI = 0.92-1.10, p = 0.87; respectively). Subgroup analyses by different platinum-based doublets indicated that the efficacy of the third-generation doublets were equal to both cisplatin-based doublets and carboplatin-based doublets (HR = 1.08, 95 % CI = 1.00-1.17, p = 0.05; HR = 1.00, 95 % CI = 0.94-1.05, p = 0.94; respectively). The secondary end points indicated that platinum-based doublets might have an advantage in PFS but not in response rate (HR = 1.06, 95 % CI = 1.01-1.12, p = 0.03; RR = 0.99, 95 % CI = 0.90-1.08, p = 0.81; respectively). Non-platinum doublets

  2. Improved survival trends in platinum-resistant patients with advanced ovarian, fallopian or peritoneal cancer treated with first-line paclitaxel/platinum chemotherapy: the impact of novel agents.

    PubMed

    Bamias, Aristotle; Bamia, Christine; Zagouri, Flora; Kostouros, Efthimios; Kakoyianni, Konstantina; Rodolakis, Alexandros; Vlahos, George; Haidopoulos, Dimitrios; Thomakos, Nikolaos; Antsaklis, Aris; Dimopoulos, Meletios-Athanasios

    2013-01-01

    The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy. Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995-31/12/2001 (n = 56) and Group B 1/1/2002-24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time. MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001). The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients. Copyright © 2012 S. Karger AG, Basel.

  3. Chemotherapy in Retinoblastoma: Current Approaches.

    PubMed

    Yanık, Özge; Gündüz, Kaan; Yavuz, Kıvılcım; Taçyıldız, Nurdan; Ünal, Emel

    2015-12-01

    Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. Although enucleation and external beam radiotherapy have been historically used, today the most commonly used eye-sparing approach is chemotherapy. Chemotherapy can be used in both intraocular and extraocular RB cases. Chemotherapeutic agents may be applied in different ways, including systemic, subconjunctival, intra-arterial and intravitreal routes. The main purposes of application of systemic therapy are to reduce the tumor size for local treatment (chemoreduction), or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). Intra-arterial chemotherapy with the current name "super-selective intra-arterial infusion therapy" could be applied as primary therapy in tumors confined to the retina or as a secondary method in tumor recurrence. The most important advantage of intra-arterial therapy is the prevention of systemic chemotherapy complications. Intravitreal chemotherapy is administered in the presence of persistent or recurrent vitreous seeding. The term "extraocular RB" includes orbital invasion and metastatic disease. Current treatment for orbital invasion is neoadjuvant chemotherapy followed by surgical enucleation and adjuvant chemotherapy and radiotherapy after surgery. In metastatic disease, regional lymph node involvement, distant metastases, and/or central nervous system (CNS) involvement may occur. Among them, CNS involvement has the worst prognosis, remaining at almost 100% mortality. In metastatic disease, high-dose salvage chemotherapy and autologous hematopoietic stem cell rescue therapy are the possible treatment options; radiotherapy could also be added to the protocol according to the side of involvement.

  4. Chemotherapy in Retinoblastoma: Current Approaches

    PubMed Central

    Yanık, Özge; Gündüz, Kaan; Yavuz, Kıvılcım; Taçyıldız, Nurdan; Ünal, Emel

    2015-01-01

    Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. Although enucleation and external beam radiotherapy have been historically used, today the most commonly used eye-sparing approach is chemotherapy. Chemotherapy can be used in both intraocular and extraocular RB cases. Chemotherapeutic agents may be applied in different ways, including systemic, subconjunctival, intra-arterial and intravitreal routes. The main purposes of application of systemic therapy are to reduce the tumor size for local treatment (chemoreduction), or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). Intra-arterial chemotherapy with the current name “super-selective intra-arterial infusion therapy” could be applied as primary therapy in tumors confined to the retina or as a secondary method in tumor recurrence. The most important advantage of intra-arterial therapy is the prevention of systemic chemotherapy complications. Intravitreal chemotherapy is administered in the presence of persistent or recurrent vitreous seeding. The term “extraocular RB” includes orbital invasion and metastatic disease. Current treatment for orbital invasion is neoadjuvant chemotherapy followed by surgical enucleation and adjuvant chemotherapy and radiotherapy after surgery. In metastatic disease, regional lymph node involvement, distant metastases, and/or central nervous system (CNS) involvement may occur. Among them, CNS involvement has the worst prognosis, remaining at almost 100% mortality. In metastatic disease, high-dose salvage chemotherapy and autologous hematopoietic stem cell rescue therapy are the possible treatment options; radiotherapy could also be added to the protocol according to the side of involvement. PMID:27800245

  5. Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer.

    PubMed

    Chen, William Tzu-Liang; Yang, Tsia-Sheng; Chen, Hung-Chang; Chen, Hong-Hwa; Chiang, Hua-Che; Lin, Tsang-Chi; Yeh, Chung-Hung; Ke, Tao-Wei; Chen, Jen-Shi; Hsiao, Koung-Hung; Kuo, Min-Liang

    2014-07-01

    Natural products, such as fermented soybeans, have been used to treat various physical conditions, including cancer. MB-6 is a botanical preparation composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract. Based on this, we hypothesized that MB-6 would increase the effectiveness of chemotherapy in patients with colon cancer. In a rodent study, MB-6, in combination with leucovorin/5-fluorouracil chemotherapy, increased the survival rate and life span of colon cancer tumor-bearing BALB/c mice as compared with treatment with chemotherapy alone. In a proof-of-concept clinical study, 72 patients with metastatic colorectal cancer were randomized to receive leucovorin, 5-fluorouracil, and oxaliplatin in combination with either MB-6 or placebo for 16 weeks. The primary outcome was the best overall response, and secondary outcomes included progression-free survival, overall survival, and adverse effects. Up to 77 weeks after treatment, there was follow-up with the patients. No significant difference in the best overall response rate and overall survival was observed between the 2 groups. Patients in the MB-6 group had a significantly lower disease progression rate than patients in the placebo group, during the study period (0.0% vs 15.8%, P = .026). The placebo group had a significantly higher incidence of adverse events at least grade 4 compared with the MB-6 group (28.9% vs 2.9%, respectively, P = .004) and a significantly higher occurrence of increased serum creatinine compared with the MB-6 group (29% vs 5.9%, P = .014). MB-6 is a promising botanical supplement that may increase the effectiveness of chemotherapy in patients with metastatic colorectal cancer.

  6. High dose chemotherapy and autologous stem cell transplantation in relapsed or refractory Hodgkin lymphoma: Emerging questions, newer agents, and changing paradigm.

    PubMed

    Akhtar, Saad

    2017-06-13

    Primary treatment for adult and pediatric patients with Hodgkin lymphoma (HL) using current multiagent anthracycline-based chemotherapy with or without radiation therapy will cure approximately >70% of the patients; >95% for early stage with a favorable risk profile and 70-75% with advanced stage and high risk features. Managing refractory and relapsed disease, however, remains a challenge. High dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) can salvage 40-70% of patients with relapsed or refractory HL. Two randomized trials in relapsed and refractory patients showed superior progression free survival. This presentation addresses some of the salient differences and changes in the management that have evolved over the last decade and have either already affected, or are likely to affect the outcome of HDC auto-SCT. The following will discussed. 1. Historic trials and other emerging issues impacting the outcome of HDC auto-SCT. 2. Changes in the primary treatment and response adapted therapy. 3. Evaluation and validation of prognostic factors at the time of first failure. 4. Selection of salvage chemotherapy. 5. Conditioning regimens. 6. Consolidation after HDC auto-SCT. 7. Management of failures of HDC auto-SCT. 8. Availability of financial resources in various healthcare systems. Enrolment in clinical trials should be encouraged. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  7. Cancer chemotherapy and pregnancy.

    PubMed

    Koren, Gideon; Carey, Nathalie; Gagnon, Robert; Maxwell, Cynthia; Nulman, Irena; Senikas, Vyta

    2013-03-01

    To promote careful education, administration, monitoring and restricted distribution when prescribing and dispensing chemotherapeutic and potentially teratogenic medications, as well as to develop clinical recommendations for the use of cancer chemotherapy in pregnant women and women of child-bearing age. To ensure that women of child-bearing age receiving chemotherapy can be appropriately counselled on the risks of becoming pregnant during treatment, and to provide guidance for health care practitioners treating pregnant women with antineoplastic agents. Published literature was retrieved through searches of PubMed or Medline, CINAHL, and The Cochrane Library in 2011, using appropriate controlled vocabulary (e.g., antineoplastic agents, neoplasms, pregnancy) and key words (e.g., cancer, neoplasms, pregnancy, chemotherapy, antineoplastic agents). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Studies were restricted to those with available English abstracts or text. Searches were updated on a regular basis and incorporated in the guideline to October 2011. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and from national and international medical specialty societies. The quality of evidence is rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). This guideline highlights the need to prevent pregnancy in women who are being treated for cancer and informs health care professionals treating pregnant women with chemotherapy of the potential risks of the therapy or ameliorated treatment protocols. Summary Statements and Recommendations Summary Statements 1. As women are postponing child-bearing, more of them are experiencing cancer in pregnancy. (II-2) 2

  8. Primary central nervous system lymphoma treated with high-dose methotrexate, high-dose busulfan/thiotepa, autologous stem-cell transplantation and response-adapted whole-brain radiotherapy: results of the multicenter Ostdeutsche Studiengruppe Hamato-Onkologie OSHO-53 phase II study.

    PubMed

    Montemurro, M; Kiefer, T; Schüler, F; Al-Ali, H K; Wolf, H-H; Herbst, R; Haas, A; Helke, K; Theilig, A; Lotze, C; Hirt, C; Niederwieser, D; Schwenke, M; Krüger, W H; Dölken, G

    2007-04-01

    We investigated the efficacy and safety of tandem high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa (HD-BuTT) with autologous peripheral blood stem-cell transplantation (aPBSCT) and response-adapted whole-brain radiation therapy (WBRT) in patients with newly diagnosed primary central nervous system lymphoma. Twenty-three patients were treated with HD-MTX on days 1 and 10. In case of at least a partial remission (PR), HD-BuTT followed by aPBSCT was given. Patients without response to induction or without complete remission (CR) after HD-BuTT received WBRT. Sixteen patients received HD-MTX and HD-BuTT achieving a CR/PR rate of 69%/13%. CR/PR rates for all patients (n = 23) were 70%/13%. There were three deaths during therapy. With longer follow-up three neurotoxic deaths occurred in irradiated patients (n = 9), while no persistent neurotoxicity was seen after HD-BuTT without subsequent WBRT. At a median follow-up of 15 months (range 1-69) median event-free survival (EFS) and overall survival (OS) for all patients were 17 and 20 months (Kaplan-Meier), after HD-BuTT 27 months and "not reached", respectively. Estimated 2-year EFS and OS were 45% and 48% for all patients versus 56% and 61% for the HD-BuTT group, respectively. MTX induction followed by HD-BuTT is an effective and very short time-on-treatment regimen. Median survival for patients treated with high-dose chemotherapy is not reached yet. The induction regimen needs optimisation. In this study WBRT was associated with a high incidence of severe neurotoxicity.

  9. A Comprehensive Assessment of Toxicities in Patients with Central Nervous System Lymphoma Undergoing Autologous Stem Cell Transplantation Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning.

    PubMed

    Scordo, Michael; Bhatt, Valkal; Hsu, Meier; Omuro, Antonio M; Matasar, Matthew J; DeAngelis, Lisa M; Dahi, Parastoo B; Moskowitz, Craig H; Giralt, Sergio A; Sauter, Craig S

    2017-01-01

    High-dose therapy and autologous stem cell transplantation (ASCT) with thiotepa, busulfan, and cyclophosphamide (TBC) conditioning has emerged as an effective postinduction treatment strategy for patients with primary central nervous system lymphoma (PCNSL) or secondary central nervous system lymphoma (SCNSL), but it is associated with considerable toxicity and transplantation-related mortality (TRM) in the modern era. Forty-three adult patients with chemosensitive PCNSL or SCNSL underwent TBC-conditioned ASCT between 2006 and 2015. Twenty-eight of these patients received pharmacokinetically (PK)-targeted busulfan dosing. The median number of clinically relevant individual grade ≥3 nonhematologic toxicities per patient was 5. We found no association between pretransplantation patient characteristics and the presence of more than 5 grade ≥3 nonhematologic toxicities. Patients with elevated first-dose busulfan area under the curve values did not experience more toxicity. Paradoxically, patients treated with more than 2 regimens before undergoing ASCT had lower first-dose busulfan AUC values. With a median follow-up among survivors of 20 months, 1-year progression-free survival (PFS) and overall survival (OS) from the time of ASCT were 83% and 87%, respectively. Although this study reaffirms the favorable PFS and OS associated with TBC-conditioned ASCT for PCNSL or SCNSL, this treatment strategy carries a large toxicity burden.

  10. Intermittent Chemotherapy as a Platform for Testing Novel Agents in Patients With Metastatic Castration-Resistant Prostate Cancer: A Department of Defense Prostate Cancer Clinical Trials Consortium Randomized Phase II Trial of Intermittent Docetaxel With Prednisone With or Without Maintenance GM-CSF.

    PubMed

    Aggarwal, Rahul R; Beer, Tomasz M; Weinberg, Vivian K; Higano, Celestia; Taplin, Mary-Ellen; Ryan, Charles J; Lin, Amy M; Alumkal, Joshi; Graff, Julie N; Nordquist, Luke T; Herrera, Isheen; Small, Eric J

    2015-06-01

    Immunotherapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), an agent that previously demonstrated antitumor activity, was evaluated within an intermittent chemotherapy framework of docetaxel with prednisone (D+P) in metastatic castration-resistant prostate cancer (mCRPC). mCRPC patients with ≥ 50% prostate-specific antigen (PSA) decline after 6 cycles of D+P were randomized to either GM-CSF or observation (Obs). At disease progression (PD), D+P was reinitiated for 6 cycles followed by the same "off chemotherapy" regimen in patients eligible for chemotherapy interruption. The sequence was repeated until PD during chemotherapy, lack of PSA response to chemotherapy, or unacceptable toxicity. The primary end point was time to chemotherapy resistance (TTCR). Of 125 patients enrolled, 52 (42%) experienced ≥ 50% PSA decline on induction D+P and were randomized to GM-CSF (n = 27) or Obs (n = 25). The median time to PD was 3.3 months (95% confidence interval [CI], 2.4-3.5) and 1.5 months (95% CI, 1.5-2.4) during the initial course of GM-CSF and Obs, respectively. Twelve of 26 (46%) patients responded to a second course of D+P. Eleven randomized patients (21%) experienced PD during chemotherapy, precluding accurate assessment of TTCR. The remaining 41 randomized patients discontinued study for lack of PSA response to chemotherapy (n = 8), patient choice to not restart chemotherapy with PSA PD (n = 13), toxicity (n = 7), or study withdrawal (n = 13). Conducting a prospective study in mCRPC with maintenance immunotherapy within the framework of intermittent chemotherapy was feasible. The use of PSA instead of radiographic end points limited the number of evaluable patients. This study provides important insight into designing contemporary intermittent chemotherapy trials with maintenance immunotherapy in patients with advanced prostate cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Understanding Chemotherapy

    MedlinePlus

    ... you may get chemotherapy before a peripheral blood stem cell transplant. Fill this section in with your doctor or nurse. I am getting chemo ... can be given in these forms: An IV (intravenously) A shot (injection) into a muscle or other part of your body A pill ...

  12. High-dose Chemotherapy and the Treatment of Metastatic Breast Cancer: Selecting the Regimen and the Source of Stem Cells.

    PubMed

    Fields; Agaliotis; Janssen; Perkins; Ballester; Hiemenz; Zorsky; Elfenbein

    1994-05-01

    High-dose chemotherapy followed by autologous stem cell rescue has been associated with an increased overall response rate and improved progression-free survival for patients with metastatic breast cancer when compared retrospectively to standard therapy. The optimal source of stem cells - peripheral blood or autologous bone marrow - has not been determined. We present results from two high-dose regimens - ifosfamide, carboplatin, and etoposide (ICE) or mitoxantrone and thiotepa (MITT) followed by autologous stem cell rescue - and analyze the outcomes for patients based on the regimen used and the source of stem cells. Disease responsiveness at the time of high-dose therapy is the most important factor for determining outcome. The source of stem cells did not affect progression-free survival for either group.

  13. Comparison of single-agent chemotherapy and targeted therapy to first-line treatment in patients aged 80 years and older with advanced non-small-cell lung cancer

    PubMed Central

    Zhang, Qianqian; Wang, Zhehai; Guo, Jun; Liu, Liyan; Han, Xiao; Li, Minmin; Fang, Shu; Bi, Xiang; Tang, Ning; Liu, Yang

    2015-01-01

    Purpose The aim of this study was to compare single-agent chemotherapy with targeted therapy in initial treatment and to explore a better choice of treatment for patients aged 80 years and older with advanced non-small-cell lung cancer (NSCLC). Patients and methods A retrospective chart review was conducted for 136 patients aged 80 years and older who were cytopathologically diagnosed and staged as advanced (stage IIIB or IV) NSCLC. The patient population was divided into two treatment groups: 78 patients were allocated to the chemotherapy group (group A, pemetrexed or gemcitabine or docetaxel as a single agent), and 60 patients were allocated to another group and received epidermal growth factor-receptor tyrosine-kinase inhibitors (group B, erlotinib or gefitinib as a single agent). The primary end points were overall survival (OS) and progression-free survival (PFS), and the secondary end points were response rate, disease-control rate, safety, and quality of life. Results In group A and group B, respectively, the median PFS was 2 versus 4 months (P=0.013), and the median OS was 8 versus 16 months (P=0.025). The 1- and 2-year survival rates of the two groups were 23.7% (group A, 18 of 76) versus 76.7% (group B, 46 of 60) and 13.2% (group A, ten of 76) versus 10% (group B, six of 60), respectively. The response rate and disease-control rate were 28.9% versus 36.7% (P=0.39) and 57.9% versus 76.7% (P=0.022) in group A and group B, respectively. Conclusion Elders aged 80 years and over with advanced NSCLC in group B had longer PFS and OS compared with group A. It was well tolerated in group B because of the mild adverse effects. Targeted therapy can be considered primarily for patients aged 80 years and older with advanced NSCLC who cannot tolerate chemotherapy or radiotherapy. PMID:25945061

  14. Chemotherapy in pregnancy.

    PubMed

    Ngu, Siew-Fei; Ngan, Hextan Y S

    2016-05-01

    Cancer diagnosed during pregnancy is uncommon, complicating between 0.02% and 0.1% of all pregnancies. Nonetheless, due to increasing age of childbearing, the incidence of cancer during pregnancy is likely to increase due to higher incidence of several age-dependent malignancies. The most common malignancies include breast cancer, cervical cancer, malignant melanoma and lymphoma. One of the key challenges in the management of cancer in pregnancy is treating the women with standard chemotherapy regimen, without compromising the safety of the developing foetus. Exposure of chemotherapy in the first trimester is associated with an increased risk of major birth defects, whereas use in the second and third trimesters is associated with intrauterine growth restriction, low birthweight and stillbirth. In this article, we review available data regarding the use of chemotherapeutic agents in pregnancy, and we summarise the neonatal outcomes, including malformations, perinatal complications and long-term follow-up. In addition, the management plan during pregnancy is also discussed.

  15. Curative cancer chemotherapy.

    PubMed

    Frei, E

    1985-12-01

    Cancer chemotherapy provides variably effective treatment for the majority of forms of human cancer and curative treatment for some 12 categories of cancer. Curative treatment is defined as the proportion of patients who survive beyond the time after which the risk of treatment failure approaches zero, i.e., the disease-free survival plateau. This progress has resulted from a closely integrated scientific effort, including drug development, pharmacology, preclinical modeling, experimental design with respect to clinical trials, quantitative criteria for response, and a series of clinical trials (initially in children with acute lymphocytic leukemia) in which the importance of complete remission, of dose and schedule, of sequencing chemotherapeutic agents, of pharmacological sanctuaries, and particularly of combination chemotherapy was studied. The principles derived from these studies, particularly those relating to combination chemotherapy, resulted in curative treatment for disseminated Hodgkin's disease, non-Hodgkin's lymphoma, pediatric solid tumors, testicular cancer, and limited small cell lung cancer. Many patients with certain stages of solid tumors, such as breast cancer and osteogenic sarcoma, are at high risk of having disseminated microscopic disease. Experimental studies indicate that treatment which is only partially effective against macroscopic disease is much more effective against microscopic tumors. Therefore chemotherapy is administered immediately following control of the primary tumor in patients at high risk of having disseminated microscopic disease, a treatment known as adjuvant chemotherapy. This program has been highly successful in increasing the cure rate in patients with pediatric solid tumors and in prolonging disease-free survival in patients with premenopausal breast cancer. Given dissemination of the technology, it is estimated that 15,000-30,000 patients per year are potentially curable in the United States. Curability of cancer

  16. 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.

  17. CHEMOTHERAPY WITH BITHIONOL-S-OXIDE IN ANIMALS INFECTED WITH PARAGONIMUS WESTERMANI.

    DTIC Science & Technology

    TREMATODES, CHEMOTHERAPY), (*PARASITIC DISEASES, CHEMOTHERAPEUTIC AGENTS), (*CHEMOTHERAPEUTIC AGENTS, PARASITIC DISEASES), EGGS, MORPHOLOGY(BIOLOGY), DOSAGE, MEDICAL EXAMINATION, HISTOLOGY, PATHOLOGY, DOGS , CATS , MONKEYS, TAIWAN

  18. [Oral complications of chemotherapy of malignant neoplasms].

    PubMed

    Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

    1999-01-01

    Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

  19. Rationale for combining immunotherapy with chemotherapy.

    PubMed

    Dalgleish, Angus G

    2015-01-01

    Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.

  20. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1991-10-01

    This document examines chemotherapeutic agents for use in veterinary oncology. It lists some of the most common categories of chemotherapeutic drugs, such as alkylating agents and corticosteroids. For each category, the paper lists some example drugs, gives their mode of action, tumors usually susceptible to the drug, and common side effects. A brief discussion of mechanisms of drug resistance is also provided. (MHB)

  1. HIV chemotherapy

    NASA Astrophysics Data System (ADS)

    Richman, Douglas D.

    2001-04-01

    The use of chemotherapy to suppress replication of the human immunodeficiency virus (HIV) has transformed the face of AIDS in the developed world. Pronounced reductions in illness and death have been achieved and healthcare utilization has diminished. HIV therapy has also provided many new insights into the pathogenesis and the viral and cellular dynamics of HIV infection. But challenges remain. Treatment does not suppress HIV replication in all patients, and the emergence of drug-resistant virus hinders subsequent treatment. Chronic therapy can also result in toxicity. These challenges prompt the search for new drugs and new therapeutic strategies to control chronic viral replication.

  2. Neoadjuvant chemotherapy for bladder cancer.

    PubMed

    Black, Peter C; Brown, Gordon A; Grossman, H Barton; Dinney, Colin P

    2006-11-01

    The 30-45% failure rate after radical cystoprostatectomy mandates that we explore and optimize multimodal therapy to achieve better disease control in these patients. Cisplatin-based multi-agent combination chemotherapy has been used with success in metastatic disease and has therefore also been introduced in patients with high-risk but non-metastatic bladder cancer. There is now convincing evidence that chemotherapy given pre-operatively can improve survival in these patients. In this review we establish the need for peri-operative chemotherapy in bladder cancer patients and summarize the evidence for the efficacy of neoadjuvant chemotherapy. The advantages and disadvantages of neoadjuvant versus adjuvant chemotherapy are discussed, and the main shortcomings of both--treatment-related toxicity and the inability to prospectively identify likely responders--are presented. Finally, a risk-adapted approach to neoadjuvant chemotherapy is presented, whereby the highest risk patients are offered treatment while those unlikely to benefit are spared the treatment-related toxicity.

  3. High-Dose Methotrexate and Cytarabine-Based Multi-Agent Chemotherapy (Modified Bonn Protocol) for Systemic Lymphoma with CNS Involvement.

    PubMed

    Umino, Kento; Fujiwara, Shin-Ichiro; Sato, Kazuya; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Hatano, Kaoru; Okazuka, Kiyoshi; Oh, Iekuni; Ohmine, Ken; Suzuki, Takahiro; Muroi, Kazuo; Kanda, Yoshinobu

    2017-01-01

    The prognosis of patients with systemic lymphoma with central nervous system (CNS) involvement is very poor and there is no established standard therapy. We retrospectively analyzed 18 patients (4 untreated and 14 relapsed) with systemic lymphoma with CNS involvement who received methotrexate and cytarabine-based multiagent chemotherapy (modified Bonn protocol). Complete and partial responses were achieved in 56 and 22% of the patients, respectively. The 1-year overall survival (OS) and progression-free survival (PFS) was 81.0 and 39.2%, respectively. Patients with parenchymal involvement showed a better 1-year PFS than those with either leptomeningeal involvement or both. In a multivariate analysis, poor performance status (PS) was the only independent prognostic factor for the 1-year OS and PFS (HR 10.8, 95% CI 1.09-108, p = 0.042; HR 20.8, 95% CI 2.39-181, p = 0.006, respectively). Grade 4 neutropenia and thrombocytopenia occurred in 17 patients each (94%), but there were no grade 4 nonhematopoietic adverse events. The modified Bonn protocol resulted in relatively favorable response and survival, and provided clinical benefits to patients with good PS, in particular. This study demonstrated that the modified Bonn protocol could be a feasible and encouraging treatment approach for lymphoma with CNS and systemic involvement.

  4. Extended Survival after Complete Pathological Response in Metastatic Pancreatic Ductal Adenocarcinoma Following Induction Chemotherapy, Chemoradiotherapy, and a Novel Immunotherapy Agent, IMM-101

    PubMed Central

    Giakoustidis, Alex; Stamp, Gordon; Gaya, Andy; Mudan, Satvinder

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. Median survival for metastatic patients is six to nine months and survivors beyond one year are exceptional. Pancreatic cancer is resistant to conventional chemotherapy and is often diagnosed at advanced stages. However, immunotherapy is a rapidly advancing new treatment modality, which shows promise in many solid tumor types.​ We present a patient with metastatic pancreatic cancer who underwent a synchronous resection of the primary tumour (pancreatoduodenectomy) and metastatic site (left hepatectomy) after multimodality neoadjuvant treatment with gemcitabine, nab-paclitaxel, and immunotherapy backbone with IMM-101 (an intradermally applied immunomodulator), as well as consolidation chemoradiation. Pathology of the specimens showed a complete response in both sites of the disease. The patient remains alive four years from the initial diagnosis and continues on maintenance immunotherapy. This exceptional response to initial chemo-immunotherapy was followed by a novel and off-protocol approach of low-dose capecitabine and IMM-101 as a maintenance strategy. The survival benefit and sustained performance status could set this as a new paradigm for the treatment of oligometastatic pancreatic cancer following response to systemic therapy and immunotherapy.​ PMID:26870619

  5. Intravenous Lidocaine Infusion to Treat Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Papapetrou, Peter; Kumar, Aashish J; Muppuri, Rudram; Chakrabortty, Shushovan

    2015-11-01

    Chemotherapy-induced peripheral neuropathy is a debilitating side effect of chemotherapy, which manifests as paresthesias, dysesthesias, and numbness in the hands and feet. Numerous chemoprotective agents and treatments have been used with limited success to treat chemotherapy-induced peripheral neuropathy. We report a case in which a patient presenting with chemotherapy-induced peripheral neuropathy received an IV lidocaine infusion over the course of 60 minutes with complete symptomatic pain relief for a prolonged period of 2 weeks.

  6. Single Agents with Designed Combination Chemotherapy Potential: Synthesis and Evaluation of Substituted Pyrimido[4,5-b]indoles as Receptor Tyrosine Kinase and Thymidylate Synthase Inhibitors and as Antitumor Agents

    PubMed Central

    Gangjee, Aleem; Zaware, Nilesh; Raghavan, Sudhir; Ihnat, Michael; Shenoy, Satyendra; Kisliuk, Roy L.

    2010-01-01

    Combinations of antiangiogenic agents (AAs) with cytotoxic agents have shown significant promise and several such clinical trials are currently underway. We have designed, synthesized and evaluated two compounds that each inhibit vascular endothelial growth factor receptor-2 (VEGFR-2) and platelet derived growth factor receptor-beta (PDGFR-β) for antiangiogenic effects and also inhibit human thymidylate synthase (hTS) for cytotoxic effects in single agents. The synthesis of these compounds involved the nucleophilic displacement of the common intermediate 5-chloro-9H-pyrimido[4,5-b]indole-2,4-diamine with appropriate benzenethiols. The inhibitory potency of both these single agents against VEGFR-2, PDGFR-β and hTS is better than or close to standards. In a COLO-205 xenograft mouse model one of the analogs significantly decreased tumor growth (TGI = 76% at 35 mg/kg), liver metastases and tumor blood vessels compared to a standard drug and to control and thus demonstrated potent tumor growth inhibition, inhibition of metastasis and antiangiogenic effects in vivo. These compounds afford combination chemotherapeutic potential in single agents. PMID:20092323

  7. Chemotherapy-induced alopecia.

    PubMed

    Trüeb, Ralph M

    2009-03-01

    Few dermatologic conditions carry as much emotional distress as chemotherapy-induced alopecia (CIA). The prerequisite for successful development of strategies for CIA prevention is the understanding of the pathobiology of CIA. The incidence and severity of CIA are variable and related to the particular chemotherapeutic protocol. CIA is traditionally categorized as acute diffuse hair loss caused by dystrophic anagen effluvium; however, CIA presents with different clinical patterns of hair loss. When an arrest of mitotic activity occurs, obviously numerous and interacting factors influence the shedding pattern. The major approach to minimize CIA is by scalp cooling. Unfortunately, most published data on scalp cooling are of poor quality. Several experimental approaches to the development of pharmacologic agents are under evaluation and include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, inhibitors of apoptosis, and cell-cycle and proliferation modifiers. Ultimately, the protection should be selective to the hair follicle; for example, topical application, such that the anticancer efficacy of chemotherapy is not hampered. Among the few agents that have been evaluated so far in humans, AS101 and minoxidil were able to reduce the severity or shorten the duration of CIA, but could not prevent CIA.

  8. Chemotherapy-induced myeloid suppressor cells and antitumor immunity: The Janus face of chemotherapy in immunomodulation.

    PubMed

    Ding, Zhi-Chun; Munn, David H; Zhou, Gang

    Tumor recurrence remains a major problem for patients with cancer, even after initial beneficial responses to standard-of-care chemotherapeutic agents. With the recent advances in immunotherapy strategies, there is growing interest in synergistically combining immunotherapy with conventional chemotherapy to achieve durable antitumor effects. In some cases, chemotherapy-induced myeloid suppressor cells represent a critical obstacle to achieving this goal.

  9. The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC)

    PubMed Central

    Yang, Jiaying; He, Jieyu; Yu, Miao; Li, Taishun; Luo, Li; Liu, Pei

    2016-01-01

    Abstract Background: Trials investigating the efficacy and safety of combining molecular targeted agent (MTA) with platinum–gemcitabine (PG) in first-line treatment of advanced non-small cell lung cancer (NSCLC) have shown inconsistent findings. This meta-analysis aimed to explore whether the addition of MTAs to PG in NSCLC could provide a survival benefit with a tolerable toxicity. Methods: Web of knowledge, PubMed, Ovid, Embase, and Cochrane Library were searched to identify relevant studies and extract data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and common grade 3 or 4 adverse events. Subgroup analyses were conducted on the basis of race and the type of MTA. Results: Twelve trials with a total of 6143 patients were included in this meta-analysis. Compared with PG chemotherapy, combination therapy of MTA with PG did not improve OS (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.90–1.01) but improved PFS (HR = 0.77, 95% CI = 0.66–0.89) and ORR (risk ratio [RR] = 1.33, 95% CI = 1.11–1.60). Subanalysis indicated that there was more incidence of grade 3 or 4 rash (RR = 11.20, 95% CI = 6.07–20.68), anemia (RR = 1.21, 95% CI = 1.01–1.46), diarrhea (RR = 2.62, 95% CI = 1.21–5.65), and anorexia (RR = 2.08, 95% CI = 1.12–3.88) in combining epidermal growth factor receptor targeted therapy group compared to PG group. An increased risk of grade 3 or 4 rash (RR = 5.08, 95% CI = 1.53–16.79), thrombocytopenia (RR = 1.50, 95% CI = 1.03–2.18), and hypertension (RR = 2.36, 95% CI = 1.05–5.32) was observed in sorafenib combination group. Conclusion: The combination of PG plus MTA was superior to PG alone in terms of PFS and ORR but not in OS. The combination chemotherapy also showed a higher frequency of grade 3 or higher toxic effects in patients with advanced NSCLC than PG chemotherapy. PMID:27977596

  10. Regorafenib as a potential adjuvant chemotherapy agent in disseminated small colon cancer: Drug selection outcome of a novel screening system using nanoimprinting 3-dimensional culture with HCT116-RFP cells.

    PubMed

    Yoshii, Yukie; Furukawa, Takako; Aoyama, Hironori; Adachi, Naoya; Zhang, Ming-Rong; Wakizaka, Hidekatsu; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2016-04-01

    Colon cancer is one of the leading causes of cancer death worldwide. Adjuvant chemotherapy following primary surgical treatment is suggested to be beneficial in eradicating invisible disseminated small tumors in colon cancer; however, an effective drug remains to be developed. Recently, we reported a novel drug screening system using a nanoimprinting 3-dimensional (3D) culture that creates multicellular spheroids, which simulate in vivo conditions and, thereby, predict effective drugs in vivo. This study aimed to perform drug selection using our recently developed 3D culture system in a human colon cancer HCT116 cell line stably expressing red fluorescent protein (HCT116-RFP), to determine the most effective agent in a selection of clinically used antitumor agents for colon cancer. In addition, we confirmed the efficacy of the selected drug regorafenib, in vivo using a mouse model of disseminated small tumors. HCT116-RFP cells were cultured using a nanoimprinting 3D culture and in vitro drug selection was performed with 8 clinically used drugs [bevacizumab, capecitabine, cetuximab, 5-fluorouracil (5-FU), irinotecan, oxaliplatin, panitumumab and regorafenib]. An in vivo study was performed in mice bearing HCT116-RFP intraperitoneally disseminated small tumors using 3'-[18F]-fluoro-3'-deoxythymidine-positron emission tomography and fluorescence microscopy imaging to evaluate the therapeutic effects. Regorafenib was determined to be the most effective drug in the 3D culture, and significantly inhibited tumor growth in vivo, compared to the untreated control and 5-FU-treated group. The drug 5-FU is commonly used in colon cancer treatment and was used as a reference. Our results demonstrate that regorafenib is a potentially efficacious adjuvant chemotherapeutic agent for the treatment of disseminated small colon cancer and, therefore, warrants further preclinical and clinical studies.

  11. Types of chemotherapy

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000910.htm Types of chemotherapy To use the sharing features on this page, ... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor ...

  12. Impact of gender on efficacy and acute toxicity of alkylating agent -based chemotherapy in Ewing sarcoma: secondary analysis of the Euro-Ewing99-R1 trial.

    PubMed

    van den Berg, Henk; Paulussen, Michael; Le Teuff, Gwénaël; Judson, Ian; Gelderblom, Hans; Dirksen, Uta; Brennan, Bernadette; Whelan, Jeremy; Ladenstein, Ruth Lydia; Marec-Berard, Perrine; Kruseova, Jarmila; Hjorth, Lars; Kühne, Thomas; Brichard, Benedicte; Wheatley, Keith; Craft, Alan; Juergens, Heribert; Gaspar, Nathalie; Le Deley, Marie-Cécile

    2015-11-01

    Based on the randomised Euro-EWING99-R1 trial, vincristine, adriamycin, cyclophosphamide (VAC) may be able to replace vincristine, adriamycin, ifosfamide (VAI) in the treatment of standard-risk Ewing sarcoma. However some heterogeneity of treatment effect by gender was observed. The current exploratory study aimed at investigating the influence of gender on treatment efficacy and acute toxicity. Impact of gender on event-free survival (EFS), acute toxicity by course, switches between treatment arms and cumulative dose of alkylating agents was evaluated in multivariable models adjusted for age including terms to test for heterogeneity of treatment effect by gender. The analysis of the EFS was performed on the intention-to-treat population. EFS did not significantly differ between the 509 males and 347 females (p=0.33), but an interaction in terms of efficacy was suspected between treatment and gender (p=0.058): VAC was associated with poorer EFS than VAI in males, hazard ratio (HR) (VAC/VAI)=1.37 [95% confidence interval (CI), 0.98-1.90], contrasting with HR=0.81 [95%CI, 0.53-1.24] in females. Severe toxicity was more frequent in females, whatever the toxicity type. Thirty patients switched from VAI to VAC (9/251 males, 4%, and 21/174 females, 12%) mostly due to renal toxicity, and three from VAC to VAI (2/258 males, 0.8%, and 1/173 females, 0.6%). A reduction of alkylating agent cumulative dose >20% was more frequent in females (15% versus 9%, p=0.005), with no major difference between VAC and VAI (10% versus 13%, p=0.15). Differences of acute toxicity rate and cumulative doses of alkylating agents could not explain the marginal interaction observed in the Euro-EWING99-R1 trial data. Effects of gender-dependent polymorphism/activity of metabolic enzymes (e.g. known for CYP2B6) of ifosfamide versus cyclophosphamide should be explored. External data are required to further evaluate whether there is heterogeneity of alkylating agent effect by gender. NCT00987636 and

  13. Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence of Candida and Aspergillus species

    PubMed Central

    Chen, Sharon C-A; Lewis, Russell E

    2011-01-01

    Conventional antineoplastic, novel immunosuppressive agents and antibiotics used in cancer treatment can directly affect the growth, development and virulence of Candida and Aspergillus species. Cytotoxic and cisplatin compounds have anti-Candida activity and may be synergistic with antifungal drugs; they also inhibit Candida and Aspergillus filamentation/conidation and effect increased virulence in vitro. Glucocorticoids enhance Candida adherence to epithelial cells, germination in serum and in vitro secretion of phospholipases and proteases, as well as growth of A. fumigatus. Calcineurin and target of rapamycin inhibitors perturb Candida and Aspergillus morphogenesis, stress responses and survival in serum, reduce azole tolerance in Candida, but yield conflicting in vivo data. Inhibition of candidal heat shock protein 90 and candidal-specific histone deacetylase represent feasible therapeutic approaches for candidiasis. Tyrosine kinase inhibitors inhibit fungal cell entry into epithelial cells and phagocytosis. Quinolone and other antibiotics may augment activity of azole and polyene agents. The correlation of in vitro effects with clinically meaningful in vivo systems is warranted. PMID:21701255

  14. Correlation of Ki-67 Proliferative Antigen Expression and Tumor Response to Induction Chemotherapy Containing Cell Cycle-Specific Agents in Head and Neck Squamous Cell Carcinoma.

    PubMed

    Chatzkel, Jonathan; Lewis, James S; Ley, Jessica C; Wildes, Tanya M; Thorstad, Wade; Gay, Hiram; Daly, Mackenzie; Jackson, Ryan; Rich, Jason; Paniello, Randal; Nussenbaum, Brian; Liu, Jingxia; Siegel, Barry A; Dehdashti, Farrokh; Adkins, Douglas

    2016-12-26

    Determine if highly proliferative head and neck squamous cell carcinomas, assessed by pretreatment Ki-67 expression, respond more robustly to induction chemotherapy (IC) that is selectively toxic to cycling cells. Retrospective analysis of 59 patients treated with IC and chemoradiation. IC included either nab-paclitaxel, cisplatin, 5-FU and cetuximab (APF-C, n = 27) or docetaxel, cisplatin, 5-FU +/- cetuximab (TPF+/-C, n = 32). Ki-67 expression was assessed by immunohistochemistry. Tumor response (complete/partial/stable/progressive) at the primary site after two IC cycles was evaluated by visual examination in all patients. In the APF-C sub-group, tumor response (primary site and neck nodes) after two IC cycles was evaluated by computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT. Ki-67 expression (median 66%, range: 16-97) did not differ across the tumor response categories assessed by visual examination (p = 0.95), CT (p = 0.30), or FDG-PET/CT (p = 0.65). Median decrease in summed SUVmax of measured lesions was 71.6% (range: 8.3-100%). The Pearson correlation coefficient between Ki-67 expression and the percent decrease in summed SUVmax was 0.48 (p = 0.02). Ki-67 expression was not different between those with or without a relapse (median: 60 and 71%, p = 0.10). In multivariate regression analysis (MVA) controlling for p16 positive oropharyngeal SCC status and smoking status, Ki-67 expression was not significantly associated with tumor response by visual examination (coefficient estimate -0.002, standard error 0.010, p = 0.84), CT (coefficient estimate -0.007, standard error 0.011, p = 0.54), FDG-PET/CT (coefficient estimate 0.006, standard error 0.008, p = 0.51), the percent decrease in summed SUVmax (coefficient estimate 0.389, standard error 0.222, p = 0.09), or relapse events (OR = 1.02(95%CI:0.99-1.05), p = 0.28). No significant relationships were found in MVA between

  15. Pregnancies and menstrual function before and after combined radiation (RT) and chemotherapy (TVPP) for Hodgkin's disease

    SciTech Connect

    Lacher, M.J.; Toner, K.

    1986-01-01

    The menstrual cycle, pregnancies, and offspring were evaluated before and after initial combined radiation (RT) and chemotherapy with thiotepa, vinblastine, vincristine, procarbazine, and prednisone (TVPP), in 34 women between the ages of 18 and 44 (median 26.5 years) treated for Stage II and Stage III Hodgkin's disease. The median range of follow-up is 83.1 months (range 40.5-140). After therapy 94.1% (32/34) continued to menstruate. Two of the four patients over the age of 35 ceased to menstruate. All patients under the age of 35 continued to menstruate (30/30). Age at the time of diagnosis was the only factor affecting change in menses with a significant probability (p = .001) that women greater than 30 years of age will experience some change in menstrual pattern. Seventeen pregnancies occurred in 12 women after therapy; 2 had 4 elective abortions; 10 delivered 12 children with normal physical development; 1 will deliver six months from now. Twelve of thirteen patients who wanted to become pregnant have conceived. The ability to become pregnant and deliver normal children after intensive treatment with combined radiation and chemotherapy (RT/TVPP) was comparable to the patients' pretreatment record.

  16. Supratentorial primitive neuroectodermal tumors (S-PNET) in children: A prospective experience with adjuvant intensive chemotherapy and hyperfractionated accelerated radiotherapy

    SciTech Connect

    Massimino, Maura . E-mail: maura.massimino@istitutotumori.mi.it; Gandola, Lorenza; Spreafico, Filippo; Luksch, Roberto; Collini, Paola; Giangaspero, Felice; Simonetti, Fabio; Casanova, Michela; Cefalo, Graziella; Pignoli, Emanuele; Ferrari, Andrea; Terenziani, Monica; Podda, Marta; Meazza, Cristina; Polastri, Daniela; Poggi, Geraldina; Ravagnani, Fernando; Fossati-Bellani, Franca

    2006-03-15

    Purpose: Supratentorial primitive neuroectodermal tumors (S-PNET) are rare and have a grim prognosis, frequently taking an aggressive course with local relapse and metastatic spread. We report the results of a mono-institutional therapeutic trial. Methods and Materials: We enrolled 15 consecutive patients to preradiation chemotherapy (CT) consisting of high-dose methotrexate, high-dose etoposide, high-dose cyclophosphamide, and high-dose carboplatin, craniospinal irradiation (CSI) with hyperfractionated accelerated radiotherapy (HART) plus focal boost, maintenance with vincristine/lomustine or consolidation with high-dose thiotepa followed by autologous stem-cell rescue. Results: Median age was 9 years; 7 were male, 8 female. Site of disease was pineal in 3, elsewhere in 12. Six patients were had no evidence of disease after surgery (NED). Of those with evidence of disease after surgery (ED), 2 had central nervous system spread. Of the 9 ED patients, 2 had complete response (CR) and 2 partial response (PR) after CT, 4 stable disease, and 1 progressive disease. Of the 7 ED patients before radiotherapy, 1 had CR, 4 PR, and 2 minor response, thus obtaining a 44% CR + PR after CT and 71% after HART. Because of rapid progression in 2 of the first 5 patients, high-dose thiotepa was systematically adopted after HART in the subsequent 10 patients. Six of 15 patients relapsed (4 locally, 1 locally with dissemination, 1 with dissemination) a mean of 6 months after starting CT, 2 developed second tumors; 5 of 6 relapsers died at a median of 13 months. Three-year progression-free survival, event-free survival, and overall survival were 54%, 34%, and 61%, respectively. Conclusion: Hyperfractionated accelerated RT was the main tool in obtaining responses in S-PNET; introducing the myeloablative phase improved the prognosis (3/10 vs. 3/5 relapses), though the outcome remained unsatisfactory despite the adoption of this intensive treatment.

  17. Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine—A chemotherapy agent

    SciTech Connect

    Gong, Xiaojuan; Moghaddam, Minoo J.; Sagnella, Sharon M.; Conn, Charlotte E.; Danon, Stephen J.; Waddington, Lynne J.; Drummond, Calum J.

    2014-09-24

    An amphiphile prodrug, 5'-deoxy-5-fluoro-N4-(palmityloxycarbonyl) cytidine or 5'-deoxy-5-fluoro-N4-(hexadecanaloxycarbonyl) cytidine (5-FCPal), consisting of the same head group as the commercially available chemotherapeutic agent Capecitabine, linked to a palmityl hydrocarbon chain via a carbamate bond is reported. Thermal analysis of this prodrug indicates that it melts at ~115 °C followed quickly by degradation beginning at ~120 °C. The neat solid 5-FCPal amphiphile acquires a lamellar crystalline arrangement with a d-spacing of 28.6 ± 0.3 Å, indicating interdigitation of the hydrocarbon chains. Under aqueous conditions, solid 5-FCPal is non-swelling and no lyotropic liquid crystalline phase formation is observed. In order to assess the in vitro toxicity and in vivo efficacy in colloidal form, solid lipid nanoparticles (SLNs) with an average size of ~700 nm were produced via high pressure homogenization. The in vitro toxicity of the 5-FCPal SLNs against several different cancer and normal cell types was assessed over a 48 h period, and IC50 values were comparable to those observed for Capecitabine. The in vivo efficacy of the 5-FCPal SLNs was then assessed against the highly aggressive mouse 4T1 breast cancer model. To do so, the prodrug SLNs were administered orally at 3 different dosages (0.1, 0.25, 0.5 mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21 days of receiving the treatments, the 0.5 mmol dose of 5-FCPal exhibited the smallest average tumour volume. Since 5-FCPal is activated in a similar manner to Capecitabine via a 3 step enzymatic pathway with the final step occurring preferentially at the tumour site, formulation of the prodrug into SLNs combines the advantage of selective, localized activation with the sustained release properties of nanostructured amphiphile self-assembly and multiple payload materials thereby potentially creating a more effective anticancer agent.

  18. Chemotherapy-induced hair loss.

    PubMed

    Trüeb, R M

    2010-01-01

    Chemotherapy-induced hair loss occurs with an estimated incidence of 65%. Forty-seven percent of female patients consider hair loss to be the most traumatic aspect of chemotherapy and 8% would decline chemotherapy due to fears of hair loss. At present, no approved pharmacologic intervention exists to circumvent this side-effect of anticancer treatment, though a number of agents have been investigated on the basis of the current understanding of the underlying pathobiology. Among the agents that have been evaluated, topical minoxidil was able to reduce the severity or shorten the duration, but it did not prevent hair loss. The major approach to minimize chemotherapy-induced hair loss is by scalp cooling, though most published data on this technique are of poor quality. Fortunately, the condition is usually reversible, and appropriate hair and scalp care along with temporarily wearing a wig may represent the most effective coping strategy. However, some patients may show changes in color and/or texture of regrown hair, and in limited cases the reduction in density may persist.

  19. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer

    PubMed Central

    Vendetti, Frank P.; Topper, Michael; Huang, Peng; Dobromilskaya, Irina; Easwaran, Hariharan; Wrangle, John; Baylin, Stephen B.; Poirier, J. T.; Rudin, Charles M.

    2015-01-01

    Recent clinical data in lung cancer suggests that epigenetically targeted therapy may selectively enhance chemotherapeutic sensitivity. There have been few if any studies rigorously evaluating this hypothesized priming effect. Here we describe a series of investigations testing whether epigenetic priming with azacitidine and entinostat increases sensitivity of NSCLC to cytotoxic agents. We noted no differences in chemosensitivity following treatment with epigenetic therapy in in vitro assays of viability and colony growth. Using cell line and patient-derived xenograft (PDX) models, we also observed no change in responsiveness to cisplatin in vivo. In select models, we noted differential responses to irinotecan treatment in vivo. In vitro epigenetic therapy prior to tumor implantation abrogated response of H460 xenografts to irinotecan. Conversely, in vitro epigenetic therapy appeared to sensitize A549 xenografts (tumor growth inhibition 51%, vs. 22% in mock-pretreated control). In vivo epigenetic therapy enhanced the response of adenocarcinoma PDX to irinotecan. Taken together, these data do not support broadly applicable epigenetic priming in NSCLC. Priming effects may be context-specific, dependent on both tumor and host factors. Further preclinical study is necessary to determine whether, and in which contexts, priming with epigenetic therapy has potential to enhance chemotherapeutic efficacy in NSCLC patients. PMID:25474141

  20. Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer.

    PubMed

    Vendetti, Frank P; Topper, Michael; Huang, Peng; Dobromilskaya, Irina; Easwaran, Hariharan; Wrangle, John; Baylin, Stephen B; Poirier, J T; Rudin, Charles M

    2015-01-01

    Recent clinical data in lung cancer suggests that epigenetically targeted therapy may selectively enhance chemotherapeutic sensitivity. There have been few if any studies rigorously evaluating this hypothesized priming effect. Here we describe a series of investigations testing whether epigenetic priming with azacitidine and entinostat increases sensitivity of NSCLC to cytotoxic agents. We noted no differences in chemosensitivity following treatment with epigenetic therapy in in vitro assays of viability and colony growth. Using cell line and patient derived xenograft (PDX) models, we also observed no change in responsiveness to cisplatin in vivo. In select models, we noted differential responses to irinotecan treatment in vivo. In vitro epigenetic therapy prior to tumor implantation abrogated response of H460 xenografts to irinotecan. Conversely, in vitro epigenetic therapy appeared to sensitize A549 xenografts (tumor growth inhibition 51%, vs. 22% in mock-pretreated control). In vivo epigenetic therapy enhanced the response of adenocarcinoma PDX to irinotecan. Taken together, these data do not support broadly applicable epigenetic priming in NSCLC. Priming effects may be context-specific, dependent on both tumor and host factors. Further preclinical study is necessary to determine whether, and in which contexts, priming with epigenetic therapy has potential to enhance chemotherapeutic efficacy in NSCLC patients.

  1. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts

    PubMed Central

    TSUKIHARA, HIROSHI; NAKAGAWA, FUMIO; SAKAMOTO, KAZUKI; ISHIDA, KEIJI; TANAKA, NOZOMU; OKABE, HIROYUKI; UCHIDA, JUNJI; MATSUO, KENICHI; TAKECHI, TEIJI

    2015-01-01

    TAS-102 is a novel oral nucleoside antitumor agent that consists of trifluridine (FTD) and tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5, and was approved in Japan in March 2014 for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, we used colorectal cancer xenografts to assess whether the efficacy of TAS-102 could be improved by combining it with bevacizumab, cetuximab or panitumumab. TAS-102 was orally administered twice a day from day 1 to 14, and bevacizumab, cetuximab and panitumumab were administered intraperitoneally twice a week for 2 weeks. Growth inhibitory activity was evaluated based on the relative tumor volume (RTV) after 2 weeks of drug administration and time taken for the relative tumor volume to increase five-fold (RTV5). Tumor growth inhibition and RTV5 with TAS-102 and bevacizumab combination treatment were significantly better than those with TAS-102 or bevacizumab alone in the SW48 and HCT116 tumor models, and the concentration of phosphorylated FTD in tumors determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was higher in the TAS-102 and bevacizumab combination group than in the TAS-102 monotherapy group. The combination of TAS-102 and cetuximab or panitumumab was also significantly more effective than either monotherapy in the SW48 tumor model. There was no significant difference in the body weight between the mice treated with TAS-102 monotherapy and any of the combination therapies on day 29. Our preclinical findings indicate that the combination therapy of TAS-102, bevacizumab and cetuximab or panitumumab is a promising treatment option for colorectal cancer. PMID:25812794

  2. Efficacy of combination chemotherapy using a novel oral chemotherapeutic agent, TAS-102, together with bevacizumab, cetuximab, or panitumumab on human colorectal cancer xenografts.

    PubMed

    Tsukihara, Hiroshi; Nakagawa, Fumio; Sakamoto, Kazuki; Ishida, Keiji; Tanaka, Nozomu; Okabe, Hiroyuki; Uchida, Junji; Matsuo, Kenichi; Takechi, Teiji

    2015-05-01

    TAS-102 is a novel oral nucleoside antitumor agent that consists of trifluridine (FTD) and tipiracil hydrochloride (TPI) at a molecular ratio of 1:0.5, and was approved in Japan in March 2014 for the treatment of patients with unresectable advanced or recurrent colorectal cancer that is refractory to standard therapies. In the present study, we used colorectal cancer xenografts to assess whether the efficacy of TAS-102 could be improved by combining it with bevacizumab, cetuximab or panitumumab. TAS-102 was orally administered twice a day from day 1 to 14, and bevacizumab, cetuximab and panitumumab were administered intraperitoneally twice a week for 2 weeks. Growth inhibitory activity was evaluated based on the relative tumor volume (RTV) after 2 weeks of drug administration and time taken for the relative tumor volume to increase five-fold (RTV5). Tumor growth inhibition and RTV5 with TAS-102 and bevacizumab combination treatment were significantly better than those with TAS-102 or bevacizumab alone in the SW48 and HCT116 tumor models, and the concentration of phosphorylated FTD in tumors determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was higher in the TAS-102 and bevacizumab combination group than in the TAS-102 monotherapy group. The combination of TAS-102 and cetuximab or panitumumab was also significantly more effective than either monotherapy in the SW48 tumor model. There was no significant difference in the body weight between the mice treated with TAS-102 monotherapy and any of the combination therapies on day 29. Our preclinical findings indicate that the combination therapy of TAS-102, bevacizumab and cetuximab or panitumumab is a promising treatment option for colorectal cancer.

  3. Efficacy of Combination Chemotherapy Using a Novel Oral Chemotherapeutic Agent, TAS-102, with Oxaliplatin on Human Colorectal and Gastric Cancer Xenografts.

    PubMed

    Nukatsuka, Mamoru; Nakagawa, Fumio; Takechi, Teiji

    2015-09-01

    TAS-102 is a novel oral nucleoside antitumor agent consisting of trifluridine (FTD) and the thymidine phosphorylase inhibitor tipiracil hydrochloride (at a molar ratio of 1:0.5) that was approved in Japan in 2014 for the treatment of unresectable advanced or recurrent colorectal cancer. In the present study, the enhancement of therapeutic efficacy using a combination of TAS-102 and oxaliplatin was evaluated in a xenograft-bearing nude mouse model of colorectal and gastric cancer. TAS-102 was orally administered twice-a-day from day 1 to 14, and oxaliplatin was administered intravenously on days 1 and 8. The in vivo growth-inhibitory activity was evaluated based on the tumor volume and the growth-delay period, was estimated based on the period required to reach a tumor volume five-times greater than the initial volume (RTV5). The tumor growth-inhibitory activity and RTV5 in mice administered TAS-102 with oxaliplatin were significantly superior to those associated with either monotherapy in mice with colorectal (HCT 116, SW-48; p<0.001) and gastric cancer (SC-2, MKN74; p<0.001). MKN74/5FU, a 5-fluorouracil-resistant MKN74 sub-line, was sensitive to both FTD and oxaliplatin in vitro. In vivo, TAS-102 alone was effective in MKN74/5FU, and its anti-tumor activity was significantly enhanced in combination with oxaliplatin (p<0.001). No significant decrease in body weight or toxicity was observed compared to either monotherapy. The present pre-clinical findings indicate that combination of TAS-102 and oxaliplatin is a promising treatment option for colorectal or gastric cancer, and can be utilized in both chemo-naïve tumors and recurrent tumors after 5-fluorouracil treatment. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial.

    PubMed

    Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Torri, Valter; Fox, Christopher P; Rosée, Paul La; Schorb, Elisabeth; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Ferrari, Angela; Linton, Kim M; Rudà, Roberta; Binder, Mascha; Pukrop, Tobias; Balzarotti, Monica; Fabbri, Alberto; Johnson, Peter; Gørløv, Jette Sønderskov; Hess, Georg; Panse, Jens; Pisani, Francesco; Tucci, Alessandra; Stilgenbauer, Stephan; Hertenstein, Bernd; Keller, Ulrich; Krause, Stefan W; Levis, Alessandro; Schmoll, Hans J; Cavalli, Franco; Finke, Jürgen; Reni, Michele; Zucca, Emanuele; Illerhaus, Gerald

    2016-05-01

    Standard treatment for patients with primary CNS lymphoma remains to be defined. Active therapies are often associated with increased risk of haematological or neurological toxicity. In this trial, we addressed the tolerability and efficacy of adding rituximab with or without thiotepa to methotrexate-cytarabine combination therapy (the MATRix regimen), followed by a second randomisation comparing consolidation with whole-brain radiotherapy or autologous stem cell transplantation in patients with primary CNS lymphoma. We report the results of the first randomisation in this Article. For the international randomised phase 2 International Extranodal Lymphoma Study Group-32 (IELSG32) trial, HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and measurable disease were enrolled from 53 cancer centres in five European countries (Denmark, Germany, Italy, Switzerland, and the UK) and randomly assigned (1:1:1) to receive four courses of methotrexate 3·5 g/m(2) on day 1 plus cytarabine 2 g/m(2) twice daily on days 2 and 3 (group A); or the same combination plus two doses of rituximab 375 mg/m(2) on days -5 and 0 (group B); or the same methotrexate-cytarabine-rituximab combination plus thiotepa 30 mg/m(2) on day 4 (group C), with the three groups repeating treatment every 3 weeks. Patients with responsive or stable disease after the first stage were then randomly allocated between whole-brain radiotherapy and autologous stem cell transplantation. A permuted blocks randomised design (block size four) was used for both randomisations, and a computer-generated randomisation list was used within each stratum to preserve allocation concealment. Randomisation was stratified by IELSG risk score (low vs intermediate vs high). No masking after assignment to intervention was used. The primary endpoint of the first randomisation was the complete remission rate, analysed by modified intention to treat. This study is registered with Clinical

  5. Managing thrombocytopenia associated with cancer chemotherapy.

    PubMed

    Kuter, David J

    2015-04-01

    Thrombocytopenia is a common problem in cancer patients. Aside from bleeding risk, thrombocytopenia limits chemotherapy dose and frequency. In evaluating thrombocytopenic cancer patients, it is important to assess for other causes of thrombocytopenia, including immune thrombocytopenia, coagulopathy, infection, drug reaction, post-transfusion purpura, and thrombotic microangiopathy. The incidence of chemotherapy-induced thrombocytopenia varies greatly depending on the treatment used; the highest rates of this condition are associated with gemcitabine- and platinum-based regimens. Each chemotherapy agent differs in how it causes thrombocytopenia: alkylating agents affect stem cells, cyclophosphamide affects later megakaryocyte progenitors, bortezomib prevents platelet release from megakaryocytes, and some treatments promote platelet apoptosis. Thrombopoietin is the main regulator of platelet production. In numerous studies, recombinant thrombopoietin raised the platelet count nadir, reduced the need for platelet transfusions, reduced the duration of thrombocytopenia, and allowed maintenance of chemotherapy dose intensity. Two thrombopoietin receptor agonists now available, romiplostim and eltrombopag, are potent stimulators of platelet production. Although few studies have been completed to demonstrate their ability to treat chemotherapy-induced thrombocytopenia, these agents may be useful in treating this condition in some situations. Chemotherapy dose reduction and platelet transfusions remain the major treatments for affected patients.

  6. Nanostructured self-assembly materials from neat and aqueous solutions of C18 lipid pro-drug analogues of Capecitabine—a chemotherapy agent. Focus on nanoparticulate cubosomes™ of the oleyl analogue

    SciTech Connect

    Gong, Xiaojuan; Moghaddam, Minoo J.; Sagnella, Sharon M.; Conn, Charlotte E.; Mulet, Xavier; Danon, Stephen J.; Waddington, Lynne J.; Drummond, Calum J.

    2014-09-24

    A series of prodrug analogues based on the established chemotherapy agent, 5-fluorouracil, have been prepared and characterized. C18 alkyl and alkenyl chains with increasing degree of unsaturation were attached to the N4 position of the 5-fluorocytosine (5-FC) base via a carbamate bond. Physicochemical characterization of the prodrug analogues was carried out using a combination of differential scanning calorimetry, cross-polarized optical microscopy, X-ray diffraction and small-angle X-ray scattering. The presence of a monounsaturated oleyl chain was found to promote lyotropic liquid crystalline phase formation in excess water with a fluid lamellar phase observed at room temperature and one or more bicontinuous cubic phases at 37 °C. The bulk phase was successfully dispersed into liposomes or cubosomes at room and physiological temperature respectively. In vitro toxicity of the nanoparticulate 5-FCOle dispersions was evaluated against several normal and cancer cell types over a 48 h period and exhibited an IC50 of -100 μM against all cell types. The in vivo efficacy of 5-FCOle cubosomes was assessed against the highly aggressive mouse 4T1 breast cancer model and compared to Capecitabine (a water-soluble commercially available 5-FU prodrug) delivered at the same dosages. After 21 days of treatment, the 0.5 mmol 5-FCOle treatment group exhibited a significantly smaller average tumour volume than all other treatment groups including Capecitabine at similar dosage. These results exemplify the potential of self-assembled amphiphile prodrugs for delivery of bioactives in vivo.

  7. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development. PMID:27773999

  8. Management of Chemotherapy Induced Nausea and Vomiting in Patients on Multiday Cisplatin Based Combination Chemotherapy

    PubMed Central

    Ranganath, Praveen; Einhorn, Lawrence; Albany, Costantine

    2015-01-01

    Introduction of cisplatin based chemotherapy has revolutionized the treatment of germ cell tumors. A common side effect of multiday cisplatin chemotherapy is severe nausea and vomiting. Considerable progress has been made in the control of these side effects since the introduction of cisplatin based chemotherapy in the 1970s. Germ cell tumor which is a model for a curable neoplasm has also turned into an excellent testing ground to develop effective strategies to prevent chemotherapy induced nausea and vomiting (CINV) in multiday cisplatin based regimens. The use of combination of a 5-hydroxytryptamine (HT)3 receptor antagonist, a neurokinin-1 (NK1) antagonist, and dexamethasone has greatly improved our ability to prevent and control acute and delayed CINV. Mechanism and pattern of CINV with multiday chemotherapy may differ from those in single day chemotherapy and therefore efficacy of antiemetic drugs as observed in single day chemotherapy may not be applicable. There are only few randomized clinical trials with special emphasis on multiday chemotherapy. Further studies are essential to determine the efficacy, optimal dose, and duration of the newer agents and combinations in multiday cisplatin based chemotherapy. PMID:26425563

  9. Chemotherapy | Smokefree.gov

    Cancer.gov

    Chemotherapy works by killing cancer cells, but healthy cells get attacked too. Damage to healthy cells can cause uncomfortable side effects. Use this action deck to get information on common chemotherapy side effects and learn how to manage them.

  10. 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

  11. Relationship of gonadal activity and chemotherapy-induced gonadal damage

    SciTech Connect

    Rivkees, S.A.; Crawford, J.D.

    1988-04-08

    The authors tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease of Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.

  12. [Chemotherapy-induced alopecia].

    PubMed

    Spaëth, Dominique; Rosso, Nathalie; Clivot, Laetitia

    2006-11-30

    Chemotherapy-induced alopecia is frequent with most chemotherapy regimens; mechanisms, evolution and small prevention tools are described. Scalp cooling (helmets or continuous cooling systems) can avoid or diminish hair loss in selected chemotherapy regimens but tolerance can be fair and long harmlessness needs to be confirmed by prospective studies. Drug prevention is only in the first steps of research.

  13. Administration of chemotherapy in patients on dialysis.

    PubMed

    Kuo, James C; Craft, Paul S

    2015-08-01

    The prevalence of patients on dialysis has increased and these patients present a challenge for chemotherapy administration when diagnosed with cancer. A consensus on the dosage and timing of different chemotherapeutic agents in relation to dialysis has not been established. We describe the pattern of care and treatment outcome for cancer patients on dialysis in our institution. The dataset from the Australia and New Zealand Dialysis and Transplant Registry of patients on dialysis who had a diagnosis of cancer was obtained and matched to the pharmacy records in our institution to identify patients who had received chemotherapy while on dialysis. Relevant clinical information including details of the dialysis regimen, chemotherapy administration and adverse events was extracted for analysis. Between July 1999 and July 2014, 21 patients on dialysis were included for analysis. Five (23.8%) received chemotherapy, most of which was administered before dialysis sessions. As a result of adverse events, one patient discontinued treatment; two other patients required dose reduction or treatment delay. Chemotherapy administration was feasible in cancer patients on dialysis, but chemotherapy usage was low. Better understanding of the altered pharmacokinetics in patients on dialysis may improve chemotherapy access and practice.

  14. Metronomic chemotherapy and immunotherapy in cancer treatment.

    PubMed

    Chen, Yu-Li; Chang, Ming-Cheng; Cheng, Wen-Fang

    2017-08-01

    Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Antineoplastic agents and thrombotic microangiopathy.

    PubMed

    Garcia, Gwenalyn; Atallah, Jean Paul

    2017-03-01

    Thrombotic microangiopathy is an uncommon but reported adverse effect of a variety of antineoplastic drugs, including chemotherapy agents such as mitomycin C and gemcitabine, and newer targeted agents such as the vascular endothelial growth factor inhibitors. We present a review of thrombotic microangiopathy associated with antineoplastic agents and its implications in current cancer therapy.

  16. Modification of chemotherapy by nitroimidazoles

    SciTech Connect

    Siemann, D.W.

    1984-09-01

    The potentiation of chemotherapeutic agents by radiation sensitizers has been extensively studied for several years. There is little doubt that the effectiveness of certain anti-cancer drugs, primarily alkylating agents, can readily be enhanced both in vitro and in vivo through the addition of a sensitizer. While enhanced effects have been observed in certain critical normal tissues, in general most animal model studies have demonstrated a therapeutic gain at large sensitizer doses. This approach to combination therapies therefore appears promising. Yet many questions concerning the interaction between chemotherapeutic agents and radiosensitizers, particularly in the aspects of modification of chemotherapy by nitroimidazoles are reviewed and discussed. These address the importance in chemopotentiation of (i) hypoxia, (ii) alterations in DNA damage and/or repair, (iii) depletion of intracellular sulfhydryls and (iv) modification of drug pharmacokinetics.

  17. Prognostic nutritional index before adjuvant chemotherapy predicts chemotherapy compliance and survival among patients with non-small-cell lung cancer

    PubMed Central

    Shimizu, Katsuhiko; Okita, Riki; Saisho, Shinsuke; Yukawa, Takuro; Maeda, Ai; Nojima, Yuji; Nakata, Masao

    2015-01-01

    Background Adjuvant chemotherapy after the complete resection of non-small-cell lung cancer (NSCLC) is now the standard of care. To improve survival, it is important to identify risk factors for the continuation of adjuvant chemotherapy. In this study, we analyzed chemotherapy compliance and magnitude of the prognostic impact of the prognostic nutritional index (PNI) before adjuvant chemotherapy. Methods We conducted a retrospective review of data from 106 patients who had received adjuvant chemotherapy. The adjuvant chemotherapy consisted of an oral tegafur agent (OT) or platinum-based chemotherapy (PB). The correlations between the PNI values and recurrence-free survival (RFS) were then evaluated. Results In the PB group, the percentage of patients who completed the four planned cycles of chemotherapy was not correlated with the PNI. In the OT group, however, a significant difference was observed in the percentage of patients who completed the planned chemotherapy according to the PNI before adjuvant chemotherapy. The RFS of patients with a PNI <50 before adjuvant chemotherapy was significantly poorer than that of the patients with a PNI ≥50. A multivariate analysis showed that nodal metastasis and PNI before chemotherapy were independent predictors of the RFS. However, PNI before surgery was not a predictor of the RFS. In the subgroup analysis, PNI before chemotherapy was independent predictor of the RFS in the OT group (P=0.019), but not in the PB group (P=0.095). Conclusion The PNI before adjuvant chemotherapy influenced the treatment compliance with the planned chemotherapy in the OT group, but not the PB group. In addition, a low PNI before adjuvant chemotherapy was associated with a poor RFS in a multivariate analysis, especially in the OT group. PMID:26504397

  18. Chemotherapy induced liver abnormalities: an imaging perspective

    PubMed Central

    Houshyar, Roozbeh; Bhosale, Priya; Choi, Joon-Il; Gulati, Rajesh; Lall, Chandana

    2014-01-01

    Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy. PMID:25320738

  19. High-dose Chemotherapy With Autologous Stem Cell Rescue in Saudi Children Less Than 3 Years of Age With Embryonal Brain Tumors.

    PubMed

    Alsultan, Abdulrahman; Alharbi, Musa; Al-Dandan, Sadeq; Bayoumi, Yasser; Alharbi, Talal; Alsudairy, Reem; Alomari, Ali; Aljamaan, Khalid; Musleh, Othman; Alharbi, Qasim; Jarrar, Mohammed

    2015-04-01

    High-dose chemotherapy with autologous stem cell rescue (HDC/ASCR) has been used in children under the age of 3 years with embryonal brain tumors to avoid or delay the use of radiation. We reviewed the medical records of 10 Saudi children less than 3 years of age with embryonal brain tumors who underwent HDC/ASCR. All 10 patients underwent surgical resection followed by 3 to 5 cycles of induction chemotherapy and 1 to 3 cycles of HDC/ASCR using carboplatin and thiotepa. Isotretinoin was used as a maintenance therapy in 4 patients. Five patients had medulloblastoma, 3 had atypical teratoid/rhabdoid tumors, 1 had an embryonal tumor with abundant neuropil and true rosettes, and 1 had pineoblastoma. The median age of the patients was 1.9 years. A total of 19 HDC/ASCR procedures were performed. Radiotherapy (RT) was administered to 5 patients after HDC/ASCR and as a salvage therapy in 1 patient. The progression-free survival rate was 50% at 1 year and at 2 years, with a median follow-up of 24 months. All 5 patients with medulloblastoma are still alive without evidence of disease, but the other patients died secondary to tumor progression. This experience suggests that strategies combining myeloablative chemotherapy and autologous stem cell rescue appear to be feasible for children with embryonal brain tumors in the Middle East.

  20. [History of cancer and chemotherapy before chemotherapy].

    PubMed

    Bonnichon, Philippe; Berger, J P; Bonni, N; Fontaine, M; Pion-Graff, J

    2014-01-01

    Chemotherapy stands today for cancer. In 1909, Paul Ehrlich (1854-1915) advocates the use of arsphenamine by infusion. So, he is considered as the father of chemotherapy. In fact, the first to have thought through chemotherapy was Sir Christopher Wren (1632-1723). In 1676, ideas and experiments on animals had sufficiently progressed to allow Michel Ettmuller (1644-1683) to publish the first edition of his book and several others were printed until 1753. In this book, he describes the first intravenous treatment, it sets the first indications, dosages and different products which can be used. However this method has been forgotten until the late 19th century.

  1. Managing adverse events in the use of bevacizumab and chemotherapy.

    PubMed

    Blowers, Elaine; Hall, Kate

    The anti-angiogenic agent bevacizumab (Avastin) has received regulatory approval for the treatment of metastatic breast cancer (MBC) in combination with the taxane chemotherapy agent paclitaxel. A range of side-effects associated with this agent have been identified across different tumour types; these are known to differ from those frequently reported with chemotherapy agents. This article is part one of a two-part literature review that was conducted to provide insight into the range, frequency and severity of adverse events that arise specifically in breast cancer when bevacizumab is combined with cytotoxic chemotherapy. PubMed and the websites of oncology conferences were searched to identify studies of bevacizumab plus chemotherapy in patients with MBC. Seventeen studies met the search criteria, including 3,836 bevacizumab-treated patients. Side-effects associated with bevacizumab included hypertension, proteinuria, thromboembolic events, bleeding and cardiac toxicity. Part two of the series will appear in the next issue of BJN.

  2. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Cancer.gov

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  3. Chemotherapy-induced peripheral neuropathy.

    PubMed

    Fehrenbacher, Jill C

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is common in patients receiving anticancer treatment and can affect survivability and long-term quality of life of the patient following treatment. The symptoms of CIPN primarily include abnormal sensory discrimination of touch, vibration, thermal information, and pain. There is currently a paucity of pharmacological agents to prevent or treat CIPN. The lack of efficacious therapeutics is due, at least in part, to an incomplete understanding of the mechanisms by which chemotherapies alter the sensitivity of sensory neurons. Although the clinical presentation of CIPN can be similar with the various classes of chemotherapeutic agents, there are subtle differences, suggesting that each class of drugs might induce neuropathy via different mechanisms. Multiple mechanisms have been proposed to underlie the development and maintenance of neuropathy; however, most pharmacological agents generated from preclinical experiments have failed to alleviate the symptoms of CIPN in the clinic. Further research is necessary to identify the specific mechanisms by which each class of chemotherapeutics induces neuropathy.

  4. Chemotherapy for advanced gastric cancer.

    PubMed

    Wagner, Anna Dorothea; Syn, Nicholas Lx; Moehler, Markus; Grothe, Wilfried; Yong, Wei Peng; Tai, Bee-Choo; Ho, Jingshan; Unverzagt, Susanne

    2017-08-29

    Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen. To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer. We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs). We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer. Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information. We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is

  5. Immunological aspects of cancer chemotherapy.

    PubMed

    Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; Kroemer, Guido

    2008-01-01

    Accumulating evidence indicates that the innate and adaptive immune systems make a crucial contribution to the antitumour effects of conventional chemotherapy-based and radiotherapy-based cancer treatments. Moreover, the molecular and cellular bases of the immunogenicity of cell death that is induced by cytotoxic agents are being progressively unravelled, challenging the guidelines that currently govern the development of anticancer drugs. Here, we review the immunological aspects of conventional cancer treatments and propose that future successes in the fight against cancer will rely on the development and clinical application of combined chemo- and immunotherapies.

  6. Chemotherapy for oral and maxillofacial tumors: an update.

    PubMed

    Eid, Ahmed; Li, Shuang; Garza, Rodolfo; Wong, Mark E

    2014-05-01

    Surgery is the primary intervention in oral and maxillofacial tumors and under ideal circumstances is curative. There is no evidence to support the use of induction or adjuvant chemotherapy in initial therapy of early stage tumors. Locally advanced tumors, non-resectable tumors as well as recurrence in early stage disease, need a multi-modality therapeutic approach involving chemotherapy. Palliative chemotherapy plays an important role in the treatment patients with metastatic oral and maxillofacial tumors. Chemotherapy and targeted agents plays an important role in the treatment of patients with rare oral and maxillofacial tumors such as sarcomas, lymphomas, and giant cell tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Chemotherapy of Tuberculosis.

    PubMed

    Dobbs, Thomas E; Webb, Risa M

    2017-04-01

    The management of tuberculosis (TB) can be a challenging process that has implications both for the affected patient and public health. Effective anti-TB chemotherapy both cures and renders the patient noncontagious. Biological factors specific to M. tuberculosis necessitate the use of multiple drugs for prolonged durations to adequately eradicate infection. Recommended regimens address the complexities of eliminating organisms from diverse reservoirs while preventing the emergence of drug resistance. First-line anti-TB therapy for drug susceptible disease effectively cures almost all patients within 6-9 months. The loss of first-line agents, due to resistance or intolerance, necessitates lengthy treatment courses, frequently 12-18 months or longer. Due to the long treatment times and the implications of missed doses, directly-observed therapy (DOT) is considered the standard of care. Drugs used for the treatment of TB have serious potential toxicities that require close monitoring and prompt response. A strong public health infrastructure and robust social supports are important elements to assure successful treatment. These numerous factors compel public health entities to take a lead role in the management of TB, either through the direct management of TB treatment or by assuring the activities of partner organizations.

  8. Chemotherapy options in castration-resistant prostate cancer

    PubMed Central

    Teply, Benjamin A.; Hauke, Ralph J.

    2016-01-01

    Introduction: The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC) is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy. Chemotherapy remains an essential component of the armamentarium. Herein, we review current chemotherapy options for patients with CRPC and discuss future challenges. Methods: We reviewed literature for chemotherapy agents in prostate cancer, with special attention to the evidence for efficacy of the currently approved agents. We also reviewed emerging data on biomarkers of response to chemotherapy for CRPC. Results: Taxanes, especially docetaxel and cabazitaxel, have first- and second-line indications for CRPC, respectively, with both providing a survival benefit. Multiple attempts to improve on the single agent efficacy of docetaxel with combination therapy have not generally been successful although platinum combinations are used for resistant phenotypes. Reductions in prostate-specific antigen by ≥30% and reductions in circulating tumor cells (CTCs) to ≤ 5 are associated with improved survival on chemotherapy. Chemotherapy may continue to be effective therapy for patients with biomarkers that are associated with resistance to androgen-directed therapies (androgen receptor splice variant 7 positivity in CTCs or high CTC heterogeneity). Conclusions: Chemotherapy remains an essential component of CRPC therapy, and biomarkers are being identified to define clinical scenarios where chemotherapy may be the optimal therapy choice. PMID:27843207

  9. The effect of cytotoxic chemotherapy on female fertility.

    PubMed

    Chasle, Sharon; How, Christine C

    2003-06-01

    Nurses are now primarily responsible for the provision of patient information, and the administration of an escalating number of cytotoxic agents. This paper aims to provide nurses with key information concerning the adverse effects of cytotoxic chemotherapy on the reproductive system of women of childbearing age. The provision of information on gonadal function and fertility is vital, particularly with the increase in the survival of women treated for cancer, and the trend towards women starting a family later in life. Gonadal toxicity of the various cytotoxic agents, disruption of the menstrual cycle, premature menopause, avoidance of pregnancy, chemotherapy in pregnancy, and fertility prospects post-chemotherapy are addressed in this paper.

  10. Chemotherapy induced nausea and vomiting--prevention and treatment.

    PubMed

    Feeney, Kynan; Cain, Michael; Nowak, Anna K

    2007-09-01

    Chemotherapy induced nausea and vomiting are among the most feared consequences of cancer treatment. Recent developments in drug treatment make the goal of no nausea or vomiting during chemotherapy realistic. In this article we review the pathogenesis and management of chemotherapy induced nausea and vomiting. Regimens to prevent chemotherapy induced nausea and vomiting are guided by the emetogenic potential of the chemotherapeutic agents used. Combined prophylactic therapy targets different pathways, improving the efficacy of prevention and treatment of chemotherapy induced nausea and vomiting. General practitioners have an important role in patients undergoing chemotherapy by reinforcing the importance of prophylactic treatment and administering rescue treatment for patients with breakthrough or prolonged nausea and vomiting postchemotherapy.

  11. Inhaled chemotherapy in lung cancer: future concept of nanomedicine.

    PubMed

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects.

  12. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  13. Brain Magnetic Resonance Imaging After High-Dose Chemotherapy and Radiotherapy for Childhood Brain Tumors

    SciTech Connect

    Spreafico, Filippo Gandola, Lorenza; Marchiano, Alfonso; Simonetti, Fabio; Poggi, Geraldina; Adduci, Anna; Clerici, Carlo Alfredo; Luksch, Roberto; Biassoni, Veronica; Meazza, Cristina; Catania, Serena; Terenziani, Monica; Musumeci, Renato; Fossati-Bellani, Franca; Massimino, Maura

    2008-03-15

    Purpose: Brain necrosis or other subacute iatrogenic reactions has been recognized as a potential complication of radiotherapy (RT), although the possible synergistic effects of high-dose chemotherapy and RT might have been underestimated. Methods and Materials: We reviewed the clinical and radiologic data of 49 consecutive children with malignant brain tumors treated with high-dose thiotepa and autologous hematopoietic stem cell rescue, preceded or followed by RT. The patients were assessed for neurocognitive tests to identify any correlation with magnetic resonance imaging (MRI) anomalies. Results: Of the 49 children, 18 (6 of 25 with high-grade gliomas and 12 of 24 with primitive neuroectodermal tumors) had abnormal brain MRI findings occurring a median of 8 months (range, 2-39 months) after RT and beginning to regress a median of 13 months (range, 2-26 months) after onset. The most common lesion pattern involved multiple pseudonodular, millimeter-size, T{sub 1}-weighted unevenly enhancing, and T{sub 2}-weighted hyperintense foci. Four patients with primitive neuroectodermal tumors also had subdural fluid leaks, with meningeal enhancement over the effusion. One-half of the patients had symptoms relating to the new radiographic findings. The MRI lesion-free survival rate was 74% {+-} 6% at 1 year and 57% {+-} 8% at 2 years. The number of marrow ablative courses correlated significantly to the incidence of radiographic anomalies. No significant difference was found in intelligent quotient scores between children with and without radiographic changes. Conclusion: Multiple enhancing cerebral lesions were frequently seen on MRI scans soon after high-dose chemotherapy and RT. Such findings pose a major diagnostic challenge in terms of their differential diagnosis vis-a-vis recurrent tumor. Their correlation with neurocognitive results deserves further investigation.

  14. Neoadjuvant chemotherapy for invasive bladder cancer.

    PubMed

    Sonpavde, Guru; Sternberg, Cora N

    2012-04-01

    Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.

  15. Mechanisms of chemotherapy-induced behavioral toxicities.

    PubMed

    Vichaya, Elisabeth G; Chiu, Gabriel S; Krukowski, Karen; Lacourt, Tamara E; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J; Walker, Adam K

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients.

  16. Mechanisms of chemotherapy-induced behavioral toxicities

    PubMed Central

    Vichaya, Elisabeth G.; Chiu, Gabriel S.; Krukowski, Karen; Lacourt, Tamara E.; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J.; Walker, Adam K.

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients. PMID:25954147

  17. Chemotherapy safety in clinical veterinary oncology.

    PubMed

    Klahn, Shawna

    2014-09-01

    Exposure to chemotherapy is a health hazard for all personnel in facilities that store, prepare, or administer antineoplastic agents. Contamination levels have been measured as much as 15 times higher in the veterinary medicine sector than in human facilities. Recent publications in human and veterinary medicine indicate that exposure extends beyond the clinic walls to affect the patient's home and family. This article provides an update on the advances in chemotherapy safety, the current issues, and the impact on cancer management in veterinary medicine. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  19. Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.

    PubMed

    Goldman, Stewart; Bouffet, Eric; Fisher, Paul G; Allen, Jeffrey C; Robertson, Patricia L; Chuba, Paul J; Donahue, Bernadine; Kretschmar, Cynthia S; Zhou, Tianni; Buxton, Allen B; Pollack, Ian F

    2015-08-01

    This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies. © 2015 by American Society of Clinical

  20. Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study

    PubMed Central

    Goldman, Stewart; Bouffet, Eric; Fisher, Paul G.; Allen, Jeffrey C.; Robertson, Patricia L.; Chuba, Paul J.; Donahue, Bernadine; Kretschmar, Cynthia S.; Zhou, Tianni; Buxton, Allen B.; Pollack, Ian F.

    2015-01-01

    Purpose This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. Patients and Methods Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation. Results The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes. Conclusion Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed nongerminomatous germ cell tumors. This regimen should be included as a backbone for further

  1. [Neoadjuvant or Adjuvant Chemotherapy for Bladder Cancer?].

    PubMed

    Hupe, M C; Kramer, M W; Kuczyk, M A; Merseburger, A S

    2015-05-01

    Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

  2. Cardiac conduction abnormalities in patients with breast cancer undergoing high-dose chemotherapy and stem cell transplantation.

    PubMed

    Ando, M; Yokozawa, T; Sawada, J; Takaue, Y; Togitani, K; Kawahigashi, N; Narabayashi, M; Takeyama, K; Tanosaki, R; Mineishi, S; Kobayashi, Y; Watanabe, T; Adachi, I; Tobinai, K

    2000-01-01

    Cardiac toxicities in 39 consecutive patients with breast cancer receiving high-dose chemotherapy (HDC) with stem cell transplantation were reviewed. All 39 patients received various anthracycline-containing regimens in adjuvant settings and/or for metastatic disease before HDC. As a cytoreductive regimen, all received cyclophosphamide 2000 mg/m2 and thiotepa 200 mg/m2 for 3 consecutive days. No immediate fatal toxicities were observed, but one patient developed chronic congestive heart failure and two had transient left ventricular dysfunction. Pericardial effusion was observed in another three patients. ST-T abnormalities during HDC were observed in two patients and arrhythmias were observed in nine, four of which occurred during stem cell infusion (SCI). There were three atrial arrhythmias, two ventricular arrhythmias, and four atrioventricular (AV)-block episodes. Two patients developed advanced and complete AV-block with an asystolic pause. Notably, three patients experienced AV-block with uncontrolled vomiting. No relationship was observed between the cumulative dose of anthracycline and cardiac toxicities during HDC. These results suggest that abnormalities in the conduction system during HDC may be more frequent than previously reported. Vagal reflex secondary to emesis may play an important role in the development of AV-block. Bone Marrow Transplantation (2000) 25, 185-189.

  3. Update for nurse anesthetists. Anesthetic implications for cancer chemotherapy.

    PubMed

    Maracic, Lindy; Van Nostrand, Joanne; Beach, Dania

    2007-06-01

    Cancer is one of the most prevalent disease processes affecting people of all ages. Cancer is the second most common cause of death in the United States, exceeded only by heart disease. Cancer survival is dependent on treatment options that may include surgery, radiation, and chemotherapy. Chemotherapy, or systemic cancer therapy, is designed to promote cell death during different phases of cell growth and division. Unfortunately, chemotherapeutic agents cannot differentiate between malignant and normal cells. Therefore, the toxic effects of chemotherapy are also seen in healthy organs and tissues. In addition, chemotherapeutic agents can interact with other medications. The effects of chemotherapy may be acute and self-limiting or chronic and present long after treatment has been completed. Patients who have had chemotherapy often undergo surgery that may or may not be related to their cancer. Chemotherapy administration can have a profound influence on anesthetic management. Safe administration of anesthesia includes knowledge of chemotherapeutic agents and their toxic effects. This course discusses the anatomic and physiologic effects of cancer chemotherapeutic agents and how they specifically affect patients receiving anesthesia.

  4. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease.

  5. Chemotherapy (For Parents)

    MedlinePlus

    ... using sunscreen. previous continue Common Side Effects (continued) Hair Loss and Scalp Sensitivity Because chemotherapy often kills the healthy cells responsible for hair growth, it's common for kids undergoing chemo to ...

  6. Cancer Chemotherapy - Multiple Languages

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Cancer Chemotherapy URL of this page: https://medlineplus.gov/languages/cancerchemotherapy.html Other topics A-Z Expand Section ...

  7. Side effects of chemotherapy in musculoskeletal oncology.

    PubMed

    Mavrogenis, Andreas F; Papagelopoulos, Panayiotis J; Romantini, Matteo; Angelini, Andrea; Ruggieri, Pietro

    2010-01-01

    With recent advances in medical and orthopedic oncology, radiation therapy and single- or multiple-agent perioperative chemotherapy are currently applied as an essential part of the multidisciplinary treatment to improve disease-free and overall survival of patients with primary and metastatic bone and soft tissue tumors. However, these treatments have led to unwanted complications. A better understanding of the effects of various antineoplastic agents on bone, soft tissue, and organs may provide the basis for the more efficacious use of antiproliferative drugs when fracture healing or allograft incorporation is required. This knowledge may also provide a rationale for concurrent treatment with drugs that protect against or compensate for adverse effects in osseous repair resulting from chemotherapy.

  8. Phase II Study of Yttrium-90-Ibritumomab Tiuxetan as Part of Reduced-Intensity Conditioning (with Melphalan, Fludarabine ± Thiotepa) for Allogeneic Transplantation in Relapsed or Refractory Aggressive B Cell Lymphoma: A GELTAMO Trial.

    PubMed

    Cabrero, Monica; Martin, Alejandro; Briones, Javier; Gayoso, Jorge; Jarque, Isidro; López, Javier; Grande, Carlos; Heras, Inmaculada; Arranz, Reyes; Bernal, Teresa; Perez-Lopez, Estefania; López-Godino, Oriana; Conde, Eulogio; Caballero, Dolores

    2017-01-01

    We designed a phase II clinical trial including Y-90 ibritumomab-tiuxetan as part of a reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (AlloSCT) in high-risk non-Hodgkin lymphoma (Clinical Trials Identifier: NCT00644371). Eligible patients had high-risk relapsed/refractory aggressive lymphoma. The conditioning regimen consisted of rituximab 250 mg (days -21 and -14), Y-90 ibritumomab IV (.4 m Ci/kg, day -14), fludarabine 30 mg/m(2) i.v. (days -3 and -2) plus melphalan 70 mg/m(2) i.v. (days -3 and -2) or 1 dose of melphalan and thiotepa 5 mg/kg (day -8). Donors were related. Eighteen patients were evaluable. At the time of transplantation, responses were complete remission (CR) (n = 7, 39%), partial remission (n = 6, 33%) or refractory disease (n = 4, 28%). Y-90-ibritumomab infusions were well tolerated, with no adverse reactions. Nonrelapse mortality at 1 year was 28%. Median follow-up was 46 (range, 39 to 55) months. Estimated 1-year progression-free survival (PFS) was 50%, and 4-year overall survival (OS) and PFS were both 44.4%. CR at the moment of AlloSCT had significant impact on PFS (71% versus 27%, P = .046) and OS (71% versus 27%, P = .047). Our results show that Y-90-ibritumomab-tiuxetan as a component of RIC for AlloSCT is feasible in patients with high-risk B cell lymphoma. Development of phase III clinical trials is needed to clarify the contribution of radioimmunotherapy to RIC AlloSCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  9. Update in Cancer Chemotherapy: Gastrointestinal Cancer—Colorectal Cancer, Part 2

    PubMed Central

    Wright, Jane C.

    1986-01-01

    An update of the state of the art of cancer chemotherapeutic treatment of gastrointestinal tract cancer is described in a multi-part series. Part 1 surveyed colorectal cancer and the use of single-agent chemotherapy in the April issue of the Journal. Part 2 of colorectal cancer will describe combination chemotherapy, preoperative and postoperative radiation, and combinations of chemotherapy and radiation, and adjuvant chemotherapy. In advanced gastrointestinal tract cancer, chemotherapy is only of palliative value with response rates generally under 50 percent and survival rates of several months to one year or more. Combination chemotherapy often produces higher response rates, yet there is no acceptable evidence that survival is improved. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers may be due to lack of data. PMID:3519988

  10. Managing oral chemotherapy: the healthcare practitioner's role.

    PubMed

    Viele, Carol S

    2007-05-01

    [corrected] Management of the side effect profiles of the new oral cancer chemotherapeutic agents differs from those of traditional oral chemotherapy and hormonal therapy. The healthcare practitioner's role in counseling and managing these toxicities as well as methods for assessing and promoting adherence is reviewed. Many side effects from traditional oral cancer chemotherapeutic agents are the result of their effects on healthy cells as well as cancer cells. The side effects from the novel targeted therapies differ from those of traditional chemotherapy. Managing side effects and patient self-administration in non-traditional settings without supervision may affect patient adherence, especially with the newer agents. Social and psychological factors also can affect adherence. Various methods are available to assess adherence, including obtaining prescription refill histories and performing pill counts. Counseling patients, asking patients to keep a diary of doses and side effects, and following up with patients at clinic visits or through telephone contact are all methods that promote adherence. Patient education should address the proper dose, frequency, timing with respect to food and other medications, what to do if a dose is missed, side effects to anticipate, and what to do if side effects occur. Healthcare practitioners play an important role in educating patients regarding potential side effects to oral chemotherapy and assessing and promoting adherence to the treatment regimen.

  11. Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases

    PubMed Central

    Passot, Guillaume; Soubrane, Olivier; Giuliante, Felice; Zimmitti, Giuseppe; Goéré, Diane; Yamashita, Suguru; Vauthey, Jean-Nicolas

    2016-01-01

    Background The liver is the most common site of metastases for colorectal cancer, and combined resection with systemic chemotherapy is the most effective strategy for survival. The aim of this article is to provide a comprehensive summary on four hot topics related to chemotherapy and surgery for colorectal liver metastases (CLM), namely: (1) chemotherapy-related liver injuries: prediction and impact, (2) surgery for initially unresectable CLM, (3) the emerging role of RAS mutations, and (4) the role of hepatic arterial infusion of chemotherapy (HAIC). Summary and Key Messages (1) The use of chemotherapy before liver resection for CLM leads to drug-specific hepatic toxicity, which negatively impacts posthepatectomy outcomes. (2) Curative liver resection of initially unresectable CLM following conversion chemotherapy should be attempted whenever possible, provided that a safe future liver remnant volume is achieved. (3) For CLM, RAS mutation status is needed to guide the use of targeted chemotherapy with anti-epithelial growth factor receptor (EGFR) agents, and is a major prognostic factor that may contribute to optimize surgical strategy. (4) HAIC agents increase the rate of objective response and the rate of complete pathological response. PMID:27995091

  12. Chemotherapy-Induced Peripheral Neuropathy: Current Status and Progress

    PubMed Central

    Brewer, Jamie R; Morrison, Gladys; Dolan, M. Eileen; Fleming, Gini F

    2015-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. PMID:26556766

  13. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    SciTech Connect

    Jeong, J; Deasy, J O

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  14. Chemotherapy-induced alopecia: advice and support for hair loss.

    PubMed

    Roe, Helen

    This article provides insight into the growth cycle of a hair follicle and the potential impact chemotherapy agents can have on this process, which often results in hair loss (alopecia). It explores the psychological consequences of chemotherapy-induced alopecia for an individual as a result of the perceptions of others as well as an individual's perception of his or her self-image. Despite the development of various forms of scalp cooling, chemotherapy-induced alopecia remains a major side effect for patients receiving chemotherapy; however, there have been improvements in wig provision and changing public opinion relating to baldness. Although chemotherapy-induced alopecia affects both males and females and all age groups, this article focuses on the potential impact for patients receiving chemotherapy as a form of treatment for breast cancer. As professionals we need to understand the social significance of hair in relation to a person's outward presentation and social interactions, along with the possible psychological implications of a person losing his or her bodily hair, and not just the head hair. We must aim to minimize the distress alopecia can cause by: ensuring we provide patients with up-to-date verbal and written information to enable them to prepare for losing their hair; helping them to preserve their self-image and minimize the psychological consequences of hair loss while receiving chemotherapy; and preparing them for their hair re-growth following completion of chemotherapy.

  15. Hepatic Artery Infusion Chemotherapy

    PubMed Central

    Schüller, J.; Kroiss, A.; Dinstl, K.

    1990-01-01

    Hepatic artery chemotherapy was given to 36 patients, using totally implantable devices consisting of a port and external pump. Twenty-seven patients had inoperable liver metastases of colorectal origin. The infusion system was inserted by laparotomy into the hepatic artery via the gastroduodenal artery. There was no operative mortality. Thirteen infusion systems could not be used for chemotherapy due to dislodgement, early death and lack of follow-up. FUdR was infused every two weeks. There were minor local complications like thrombosis of the system and dislodgement of the port. Toxic effects could be managed by reducing the dose. Response to chemotherapy was evaluated by survival, clinical condition, CEA, ultrasound and CT six months after onset of arterial chemotherapy. Ten/twenty-three patients (43%) responded to therapy, eight of them died on the average 19 months after initial chemotherapy. Six patients were non-responders, seven had stable disease. Five/ten patients developed extrahepatic metastases. Mean survival time was 13.1 months, mean interval until relapse 10.6 months. PMID:2149279

  16. Safe handling of chemotherapy in the perioperative setting.

    PubMed

    Mellinger, Ellice; Skinker, Linda; Sears, Diane; Gardner, Diane; Shult, Piya

    2010-04-01

    Safe handling of chemotherapeutic agents during administration and disposal is critical. Most antineoplastic agents are toxic compounds that are carcinogenic, mutagenic, or teratogenic. Direct contact may cause irritation of the skin, eyes, and mucous membranes. Perioperative personnel should know how to handle hazardous materials safely to protect the patient, other staff members, and themselves. These safety precautions include appropriately identifying the patient; correctly preparing, verifying, and documenting the chemotherapeutic agents being administered; consistently wearing personal protective equipment; transporting the chemotherapeutic agent in a puncture-resistant container labeled "chemotherapy"; properly disposing of the chemotherapeutic agent and supplies; and handling a spill if one occurs.

  17. Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for High-Grade Gliomas in Children and Adolescents

    PubMed Central

    2017-01-01

    With the aim to investigate the outcome of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) for high-grade gliomas (HGGs), we retrospectively reviewed the medical records of 30 patients with HGGs (16 glioblastomas, 7 anaplastic astrocytomas, and 7 other HGGs) between 2006 and 2015. Gross or near total resection was possible in 11 patients. Front-line treatment after surgery was radiotherapy (RT) in 14 patients and chemotherapy in the remaining 16 patients including 3 patients less than 3 years of age. Eight of 12 patients who remained progression free and 5 of the remaining 18 patients who experienced progression during induction treatment underwent the first HDCT/auto-SCT with carboplatin + thiotepa + etoposide (CTE) regimen and 11 of them proceeded to the second HDCT/auto-SCT with cyclophosphamide + melphalan (CyM) regimen. One patient died from hepatic veno-occlusive disease (VOD) during the second HDCT/auto-SCT; otherwise, toxicities were manageable. Four patients in complete response (CR) and 3 of 7 patients in partial response (PR) or second PR at the first HDCT/auto-SCT remained event free: however, 2 patients with progressive tumor experienced progression again. The probabilities of 3-year overall survival (OS) after the first HDCT/auto-SCT in 11 patients in CR, PR, or second PR was 58.2% ± 16.9%. Tumor status at the first HDCT/auto-SCT was the only significant factor for outcome after HDCT/auto-SCT. There was no difference in survival between glioblastoma and other HGGs. This study suggests that the outcome of HGGs in children and adolescents after HDCT/auto-SCT is encouraging if the patient could achieve CR or PR before HDCT/auto-SCT. PMID:28049229

  18. The 20th International Congress of Chemotherapy.

    PubMed

    Hunter, P A

    1997-09-01

    Over 4,000 participants from all over the world attended the 20th International Congress of Chemotherapy (ICC) between 29th June-3rd July, 1997, in Sydney. Anti-infective and cancer chemotherapy were discussed in a wide context, with presentations being made on new products, compounds in development and current clinical approaches. Inevitably in a congress of this size, there were many sessions running concurrently (usually nine), with several simultaneous poster sessions as well. A common theme currently at many chemotherapy congresses is the growth of resistance to existing agents, and the ICC was no exception. Resistance to Gram-positive cocci is a particular problem, and many sessions were devoted to this subject. This report attempts to highlight just some of the aspects of antibacterial chemotherapy presented at the meeting. New fluoroquinolones formed a major topic that attracted a number of poster sessions and symposia, continuing a trend seen in recent years. The streptogramins offer an alternative approach to combating Gram-positive infections, and a symposium was devoted to these compounds.

  19. An overview of randomised controlled trials of adjuvant chemotherapy in head and neck cancer.

    PubMed Central

    Munro, A. J.

    1995-01-01

    Meta-analysis of the published results from 54 randomised controlled trials of adjuvant chemotherapy in head and neck cancer suggests that chemotherapy might increase absolute survival by 6.5% (95% confidence interval 3.1-9.9%). The odds ratio in favour of chemotherapy is 1.37 (95% confidence interval 1.24-1.5). Single-agent chemotherapy given synchronously with radiotherapy increased survival by 12.1% (95% confidence interval 5-19%). The benefit from neoadjuvant chemotherapy was less: a rate difference of 3.7% (95% confidence interval 0.9-6.5%). The results suggest that the investigation of optimal agents and scheduling for synchronous radiotherapy and chemotherapy might still be important in clinical trials in head and neck cancer. PMID:7819055

  20. Managing Chemotherapy Side Effects: Pain

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If you ... to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each day, ...

  1. Managing Chemotherapy Side Effects: Infection

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Infection “I am extra careful to stay away ... doctor or nurse right away. Managing Chemotherapy Side Effects: Infection Take these steps to lower your chances ...

  2. Combination chemotherapy for advanced bilharzial bladder carcinoma.

    PubMed

    Khaled, H M; Gad el-Mawla, N; el-Said, A; Hamza, M R; Gaafar, R; el-Attar, I; Abu Rabia, A; Magrath, I

    1996-09-01

    Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently, largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of the most active agents were administered in alternating cycles to patients who had never received chemotherapy. The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females, with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks. Among the 22 evaluable patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three more patients had responses that were less than a partial remission, and 6 patients showed disease stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the delivered dose intensity. No relationship was found between any of these parameters and response to therapy. Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete remission and prolonged survival is rare in this subgroup of patients with

  3. Chemotherapy of herpesvirus infections.

    PubMed

    Jawetz, E

    1975-07-01

    Herpesviruses commonly produce lesions that come to the attention of physicians. Many different chemicals are known to suppress the growth of herpesviruses in vitro, but only a few of these have found application in clinical practice. A critical assessment of the place of some of these forms of chemotherapy was briefly presented.

  4. Treatment-induced cell cycle kinetics dictate tumor response to chemotherapy

    PubMed Central

    Hallett, Robin M.; Huang, Cheng; Motazedian, Ali; Auf der Mauer, Stefanie; Pond, Gregory R.; Hassell, John A.; Nordon, Robert E.; Draper, Jonathan S.

    2015-01-01

    Chemotherapy fails to provide durable cure for the majority of cancer patients. To identify mechanisms associated with chemotherapy resistance, we identified genes differentially expressed before and after chemotherapeutic treatment of breast cancer patients. Treatment response resulted in either increased or decreased cell cycle gene expression. Tumors in which cell cycle gene expression was increased by chemotherapy were likely to be chemotherapy sensitive, whereas tumors in which cell cycle gene transcripts were decreased by chemotherapy were resistant to these agents. A gene expression signature that predicted these changes proved to be a robust and novel index that predicted the response of patients with breast, ovarian, and colon tumors to chemotherapy. Investigations in tumor cell lines supported these findings, and linked treatment induced cell cycle changes with p53 signaling and G1/G0 arrest. Hence, chemotherapy resistance, which can be predicted based on dynamics in cell cycle gene expression, is associated with TP53 integrity. PMID:25749523

  5. Global chemotherapy development for gastric cancer.

    PubMed

    Harada, Kazuto; Mizrak Kaya, Dilsa; Shimodaira, Yusuke; Ajani, Jaffer A

    2017-03-01

    To combat the dismal mortality rates from metastatic gastric adenocarcinoma (GAC), new drugs and treatment strategies are needed. Today, metastatic GAC is predominantly treated by empiric chemotherapy. Combination of two cytotoxic agents has become commonplace in North America, Europe, and Asia. Human epidermal growth factor 2 (HER2) overexpression (protein or gene copy numbers) has resulted in the addition of trastuzumab in the first-line chemotherapy combination in patients whose tumor is HER2 positive. The addition of trastuzumab in this select population has provided a modest survival advantage. In this review we trace the global development of systemic therapy in patients with metastatic GAC and ponder what lies in the future.

  6. High-dose chemotherapy and autologous stem cell transplantation for primary central nervous system lymphoma: a multi-centre retrospective analysis from the United Kingdom.

    PubMed

    Kassam, S; Chernucha, E; O'Neill, A; Hemmaway, C; Cummins, T; Montoto, S; Lennard, A; Adams, G; Linton, K; McKay, P; Davies, D; Rowntree, C; Easdale, S; Eyre, T A; Marcus, R; Cwynarski, K; Fox, C P

    2017-09-01

    The prognosis of patients with primary central nervous system lymphoma (PCNSL) has improved in recent years. This has partly been achieved by remission induction protocols incorporating high-dose methotrexate (HD-MTX) and rituximab. Given the high rates of relapse, consolidation therapy is usually considered in first response. Whole brain radiotherapy may prolong PFS but appears to confer no long-term survival advantage and is associated with significant neurocognitive dysfunction. Attempts to improve efficacy and reduce neurotoxicity of consolidation therapy have included thiotepa-based high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT). This multi-centre, retrospective study reports the outcome of 70 patients undergoing HDC-ASCT for PCNSL in the United Kingdom. The median age at diagnosis was 56 years and all patients received HD-MTX-containing induction regimens. All patients underwent HDC-ASCT in first response. The rate of complete response increased from 50% before HDC-ASCT to 77% following HDC-ASCT. Treatment-related mortality was 6%. At a median follow-up of 12 months from HDC-ASCT, the estimated 1- and 2-year PFS rates were 71.5% and overall survival 86.4% and 83.3%, respectively. These data are comparable to published studies of HDC-ASCT for PCNSL, supporting its feasibility and efficacy.

  7. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

  8. [Prevention and control of chemotherapy-induced nausea and vomiting].

    PubMed

    Gómez-Raposo, César; Feliú-Batlle, Jaime; Feliú-Batle, Jaime; González-Baróna, Manuel

    2006-02-04

    Nausea and vomiting are considered one of the most distressing side-effects of chemotherapy. Complete control of acute and delayed emesis improves quality of life and increases adherence to treatment. The frequency of nausea and vomiting depends primarily on the emetogenic potential of the chemotherapeutic agents used. With the standard antiemetic therapy (5HT-3 receptor antagonists in combination with dexamethasone) approximately 13% of patients receiving chemotherapy have vomiting in the acute phase and almost 50% in the delayed phase. A new group of antiemetic drugs, the neurokinin-1 receptor antagonists, in combination with standard therapy significantly improves emesis protection in the acute and in the delayed phase, although control of nausea is not so effective. Nowadays chemotherapy-induced emesis still occurs. Recent developments in antiemetic therapy and responsibility to achieve the best control of nausea and vomiting in patients receiving chemotherapy justified a review of this problem, which is frequently underestimated by physicians and nurses.

  9. Combination versus sequential single agent chemotherapy in advanced breast cancer: associations with metastatic sites and long-term survival. The Western Cancer Study Group and The Southeastern Cancer Study Group.

    PubMed Central

    Chlebowski, R. T.; Smalley, R. V.; Weiner, J. M.; Irwin, L. E.; Bartolucci, A. A.; Bateman, J. R.

    1989-01-01

    Two hundred and twenty-two patients with advanced breast cancer were randomised in two separate trials of similar design to either concomitant combination treatment or sequential use of the same drugs given as single agents changed only at disease progression. Both trials used cyclophosphamide, methotrexate, 5-fluorouracil and prednisone; the WCSG using triiodothyronine and the SECSG using vincristine as the remaining agent. A common data base was generated for these trials and combined for analysis. Considering all patients, combination treatment was associated with a significantly increased response (46 versus 25%, P less than 0.05) but not survival improvement. For the 141 patients without liver involvement, survival was closely comparable in both treatment arms. Combination therapy did result in significant survival benefit for patients with liver involvement (P less than 0.05). These studies demonstrate: (1) in the majority of breast cancer patients, sequential single agent therapy can result in survival comparable to combination treatment; and (2) sole consideration of response frequency does not represent the optimal criterion to compare therapeutic approaches in advanced breast cancer. PMID:2649130

  10. Chemotherapy for cholangiocarcinoma: An update.

    PubMed

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-07-15

    tumor effects. Nowadays, no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma. There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma. In systemic therapy, no single drug or combination has consistently increased median survival beyond the expected 8-12 mo. It is always recommended that patients enrol in clinical trials. Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin (or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone. Leucovorin-modulated 5-fluorouracil, capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status. After progression in patients with an adequate performance status, active regimens that could be considered include gemcitabine plus capecitabine, or erlotinib plus bevacizumab, for second line treatment.

  11. Chemotherapy for cholangiocarcinoma: An update

    PubMed Central

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-01-01

    tumor effects. Nowadays, no neoadjuvant therapy can be considered a standard approach for the treatment of patients with cholangiocarcinoma. There are promising results and randomized trials are needed in patients with a metastatic cholangiocarcinoma. In systemic therapy, no single drug or combination has consistently increased median survival beyond the expected 8-12 mo. It is always recommended that patients enrol in clinical trials. Clinical trials have shown that the more standard chemotherapy for a first line regimen of gemcitabine plus cisplatin (or oxaliplatin as a potentially better tolerated agent) is superior to gemcitabine alone. Leucovorin-modulated 5-fluorouracil, capecitabine monotherapy or single agent gemcitabine are reasonable options for patients with a borderline performance status. After progression in patients with an adequate performance status, active regimens that could be considered include gemcitabine plus capecitabine, or erlotinib plus bevacizumab, for second line treatment. PMID:23919111

  12. Chemotherapy of Leishmaniasis.

    DTIC Science & Technology

    1978-12-01

    NOTES 1S. KEY WORDS (Continue on reverse side linscoeawy and identiIIy by block number) LEISHMANIA LEISHMANIASIS CHEMOTHERAPY ANTILEISHMANIAL PENTOSTAM...number of compounds was supplied by WRAIR for testing on four strains of Leishmania in December 1977. Preliminary data were supplied to WRAIR by the...1 Visceral leishmaniasis The laboratory model used for the investigation of drug activity against visceral infection in this laboratory is L. donovani

  13. Chemotherapy of Cutaneous Leishmaniasis

    DTIC Science & Technology

    2012-10-01

    bacterial emerging diseases. 43rd Annual Commonwealth Caribbean Medical Research Council Meeting. Ocho Rios, Jamaica, April, 1998. Palmer, C.J., J...1 Award Number: W81XWH-10-2-0196 TITLE: CHEMOTHERAPY OF CUTANEOUS LEISHMANIASIS PRINCIPAL INVESTIGATOR: DR. ARBA AGER CONTRACTING ...Respondents should be aware that notwithstanding any other provision of law , no person shall be subject to any penalty for failing to comply with a

  14. Hyperammonemic encephalopathy after chemotherapy. Survival after treatment with sodium benzoate and sodium phenylacetate.

    PubMed

    del Rosario, M; Werlin, S L; Lauer, S J

    1997-12-01

    A 16-year-old boy had hyperammonemia and encephalopathy develop after high-dose chemotherapy for acute lymphoblastic leukemia. He was treated successfully with the ammonia-trapping agents sodium benzoate and sodium phenylacetate.

  15. Use of maintenance endocrine therapy after chemotherapy in metastatic breast cancer.

    PubMed

    Sutherland, S; Miles, D; Makris, A

    2016-12-01

    For women with oestrogen receptor+ metastatic breast cancer (MBC), the options for systemic treatment include endocrine therapy (ET) and chemotherapy. For women whose disease is also HER2+, anti-HER2 therapies are also routinely used either with chemotherapy or less commonly with ET. Where chemotherapy is used as initial therapy, treatment is often discontinued due to cumulative toxicity in the absence of disease progression. In this setting, there is the option of introducing ET with the aim of prolonging response and delaying relapse. Literature review revealed four trials addressing the question of whether there is a benefit from introducing ET following chemotherapy for MBC. We also sought evidence for alternative approaches, including concurrent chemotherapy and ET and continuing chemotherapy until disease progression. The evidence for the use of ET after chemotherapy in MBC is limited, and the trials done were small. Furthermore, they were performed at a time when both the chemotherapy regimens and ET were different from those used currently. Despite these limitations, there is probably a modest improvement in time to progression for the sequential use of ET after chemotherapy but with no overall survival benefit. An alternative approach, particularly considering agents with relatively low toxicity, such as orally bioavailable fluoropyrimidines, is to continue chemotherapy until disease progression. Where chemotherapy for MBC is discontinued due to toxicity, in the absence of progression, the use of ET, with its relatively low toxicity, is a reasonable approach with the aim of delaying relapse. Copyright © 2016. Published by Elsevier Ltd.

  16. Chemotherapy and molecular targeting therapy for recurrent cervical cancer.

    PubMed

    Tsuda, Naotake; Watari, Hidemichi; Ushijima, Kimio

    2016-04-01

    For patients with primary stage ⅣB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: "uterine cervical cancer", "chemotherapy", and "targeted therapies". Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase Ⅲ trials. To examine the best agent to combine with cisplatin, several landmark phase Ⅲ clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments offer only

  17. Comparison of Intensive Chemotherapy and Hypomethylating Agents before Allogeneic Stem Cell Transplantation for Advanced Myelodysplastic Syndromes: A Study of the Myelodysplastic Syndrome Subcommittee of the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplant Research.

    PubMed

    Potter, Victoria T; Iacobelli, Simona; van Biezen, Anja; Maertens, Johann; Bourhis, Jean-Henri; Passweg, Jakob R; Yakhoub-Agha, Ibrahim; Tabrizi, Reza; Bay, Jacques-Olivier; Chevallier, Patrice; Chalandon, Yves; Huynh, Anne; Cahn, Jean Yves; Ljungman, Per; Craddock, Charles; Lenhoff, Stig; Russell, N H; Fegueux, Nathalie; Socié, Gerard; Benedetto, Bruno; Meijer, Ellen; Mufti, G J; de Witte, Theo; Robin, Marie; Kröger, Nicolaus

    2016-09-01

    The European Society for Blood and Marrow Transplant Research data set was used to retrospectively analyze the outcomes of hypomethylating therapy (HMA) compared with those of conventional chemotherapy (CC) before hematopoietic stem cell transplantation (HSCT) in 209 patients with advanced myelodysplastic syndromes. Median follow-up was 22.1 months and the median age of the group was 57.6 years with 37% of the population older than > 60 years. The majority of patients (59%) received reduced-intensity conditioning and 34% and 27% had intermediate-2 and high international prognostic scoring system (IPSS) scores. At time of HSCT, 32% of patients did not achieve complete remission (CR) and 13% had primary refractory disease. On univariate analysis, outcomes at 3 years were not significantly different between HMA and CC for overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM): OS (42% versus 35%), RFS (29% versus 31%), CIR (45% versus 40%), and NRM (26% versus 28%). Comparing characteristics of the groups, there were more patients < 55 years old, more patients in CR (68% versus 32%), and fewer patients with primary refractory disease in the CC group than in the HMA group (10% versus 19%, P < .001). Patients with primary refractory disease had worse outcomes than those in CR with regard to OS (hazard ratio [HR], 2.42; 95% confidence interval [CI], 1.41 to 4.13; P = .001), RFS (HR, 2.27; 95% CI, 1.37 to 3.76; P = .001), and NRM (HR, 2.49; 95% CI, 1.18 to 5.26; P = .016). In addition, an adverse effect of IPSS-R cytogenetic risk group was evident for RFS. In summary, outcomes after HSCT are similar for patients receiving HMA compared with those receiving CC, despite the higher proportion of patients with primary refractory disease in the HMA group. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Optimizing chemotherapy for patients with advanced breast cancer.

    PubMed

    Marty, M; Espie, M; Cottu, P H; Cuvier, C; Lerebours, F

    1999-07-01

    Chemotherapy is offered to almost all patients with metastatic breast cancer. Optimization of treatment has four major goals: (1) To improve access to chemotherapy. Orally active chemotherapy is an attractive option for those patients when access to hospital is limited by financial considerations, long journeys or patient reluctance. In the past, only alkylating agents (cyclophosphamide, chlorambucil, melphalan) could be administered orally. The activity (first- and second-line) of Xeloda (capecitabine) with limited side effects and the development of oral vinorelbine and anthracyclines should improve access to chemotherapy and also concentrate further interest on treatment with long-term administration of cytotoxic agents. (2) To improve response rates and duration in first-line treatment. Response rates have been increased by the use of combinations of taxoids and anthracyclines and/or alkylating agents and/or fluoropyrimidines (>60-70% with complete remission in 10-15% of patients). There is increasing interest in sequential use of active agents or combinations at their optimal doses. Nevertheless, such 'induction regimen' fail to prolong response duration (rarely longer than 9-12 months). The use of less-toxic maintenance chemotherapy regimens increases response duration and disease-free survival. Such maintenance regimens could be used on an outpatient basis and will be further simplified by the availability of active oral agents such as the novel fluoropyrimidine Xeloda. (3) To increase cure rates. This can only be considered with first-line treatment in selected patients (long disease-free interval, minimal number of visceral sites and ability to tolerate high-dose chemotherapy). The completed studies with high-dose chemotherapy and hematopoietic stem cell support have, in fact, shown only a minimal effect on cure rates. Incorporation of very active agents such as taxoids and use of multicycle high-dose therapy may improve these results. (4) To offer

  19. A case series of patients on chemotherapy with dyspnoea and pulmonary infiltrates

    PubMed Central

    Ullah, Khalil; O'Reilly, Aine; Power, Derek G; O'Connor, Terence M

    2013-01-01

    Clinicians often assume that patients who develop pulmonary symptoms and radiographic infiltrates while receiving cytotoxic chemotherapy have opportunistic pulmonary infection or chemotherapy-related interstitial lung disease. We describe two cases of rare complications of commonly used chemotherapeutic agents (gemcitabine-induced eosinophilic pneumonia and rituximab-induced hypersensitivity pneumonitis) that vindicate this assumption but a third case of scleroderma-associated interstitial lung disease that became clinically manifest in a patient who was receiving chemotherapy. The latter case highlights the need for vigilance for other causes of interstitial lung disease in patients receiving chemotherapy. PMID:23744855

  20. Efficacy of Scalp Cooling in Preventing Chemotherapy-Induced Alopecia in Breast Cancer Patients Receiving Adjuvant Docetaxel and Cyclophosphamide Chemotherapy.

    PubMed

    Cigler, Tessa; Isseroff, Devora; Fiederlein, Barbara; Schneider, Sarah; Chuang, Ellen; Vahdat, Linda; Moore, Anne

    2015-10-01

    Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of many chemotherapy agents. The TC (docetaxel [Taxotere] and cyclophosphamide) chemotherapy regimen is typically associated with complete alopecia. Scalp cooling with cold caps has been reported to minimize or prevent CIA. We conducted a prospective study to assess efficacy of scalp cooling in preventing CIA among women receiving adjuvant TC chemotherapy for breast cancer. Women at the Weill Cornell Breast Center who independently elected to use scalp cooling with cold caps during adjuvant TC chemotherapy were asked to participate. Degree of hair loss was assessed by a single practitioner using Dean's alopecia scale (grade 1/excellent [< 25% hair loss], grade 2/good [25%-50% hair loss], grade 3/moderate [50%-75% hair loss], grade 4/poor [> 75% hair loss]), by digital photographs, and by patient self-report of hair thinning or the need to wear a wig/head covering, or both. Assessments were made before each chemotherapy treatment and at follow-up visits between 3 weeks and 3 months after completion of chemotherapy. Of 20 evaluable patients, 10% reported a need to wear a wig/head covering at the follow-up visit. Dean's alopecia score was excellent for 65% of patients, good for 25% of patients, and moderate or poor for 10% of patients. The majority of patients reported hair thinning after every chemotherapy cycle. No patient discontinued therapy because of an intolerance to cold caps. Scalp cooling with cold caps appears to be effective in preventing CIA among the majority of women undergoing treatment with TC chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Chemotherapy of trypanosomiases and leishmaniasis.

    PubMed

    Croft, Simon L; Barrett, Michael P; Urbina, Julio A

    2005-11-01

    New formulations, therapeutic switching of the established drugs amphotericin B and paromomycin, and the serendipitous discovery of miltefosine have markedly improved leishmaniasis chemotherapy in the past 21 years. The situation for the two trypanosomiases has been less encouraging. Apart from the introduction of eflornithine for the treatment of late-stage human African trypanosomiasis, with its serious limitations in terms of cost and difficulty of administration, no new drugs have been incorporated into the chemotherapeutic arsenal in the past 25 years, despite important advances in knowledge of the biology of the etiological agents and the pathophysiology of these diseases. In the case of Chagas disease, several classes of compound that target the validated biochemical pathways of the parasite (e.g. inhibitors of sterol biosynthesis and cysteine proteases) are in the pipeline. With the availability of complete genome sequences for all three pathogens, and methods for rapid validation of targets, it is hoped that much-needed amelioration will occur soon. Financial constraints continue to represent a major hurdle to drug development. However, the appearance of not-for-profit product-development partnerships offers a new paradigm for bringing new drugs to patients.

  2. Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

    PubMed

    Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar

    2012-05-01

    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

  3. Bone marrow osteoblast vulnerability to chemotherapy.

    PubMed

    Gencheva, Marieta; Hare, Ian; Kurian, Susan; Fortney, Jim; Piktel, Debbie; Wysolmerski, Robert; Gibson, Laura F

    2013-06-01

    Osteoblasts are a major component of the bone marrow microenvironment, which provide support for hematopoietic cell development. Functional disruption of any element of the bone marrow niche, including osteoblasts, can potentially impair hematopoiesis. We have studied the effect of two widely used drugs with different mechanisms of action, etoposide (VP16) and melphalan, on murine osteoblasts at distinct stages of maturation. VP16 and melphalan delayed maturation of preosteoblasts and altered CXCL12 protein levels, a key regulator of hematopoietic cell homing to the bone marrow. Sublethal concentrations of VP16 and melphalan also decreased the levels of several transcripts which contribute to the composition of the extracellular matrix (ECM) including osteopontin (OPN), osteocalcin (OCN), and collagen 1A1 (Col1a1). The impact of chemotherapy on message and protein levels for some targets was not always aligned, suggesting differential responses at the transcription and translation or protein stability levels. As one of the main functions of a mature osteoblast is to synthesize ECM of a defined composition, disruption of the ratio of its components may be one mechanism by which chemotherapy affects the ability of osteoblasts to support hematopoietic recovery coincident with altered marrow architecture. Collectively, these observations suggest that the osteoblast compartment of the marrow hematopoietic niche is vulnerable to functional dysregulation by damage imposed by agents frequently used in clinical settings. Understanding the mechanistic underpinning of chemotherapy-induced changes on the hematopoietic support capacity of the marrow microenvironment may contribute to improved strategies to optimize patient recovery post-transplantation.

  4. Caregiver survey results related to handling of oral chemotherapy for pediatric patients with acute lymphoblastic leukemia.

    PubMed

    Held, Kristin; Ryan, Robin; Champion, Judy M; August, Keith; Radhi, Mohamed A

    2013-08-01

    Oral chemotherapy is commonly administered in the home; however, there may be harmful effects on healthy individuals who handle these medications. Caregivers of pediatric patients were surveyed to establish educational needs for safe handling of oral chemotherapy agents. An 11-question self-report survey was developed to characterize handling practices for patients in maintenance therapy for acute lymphoblastic leukemia related to caregiver education, use of protective gear, preparation, and disposal of oral chemotherapy agents. Fifty questionnaires were collected. Seventy-two percent of responders reported receiving instruction on safe handling of oral chemotherapy. Ninety percent of responders reported that they did not utilize protective gear during preparation of oral chemotherapy. Although tablet crushers were designated for use with oral chemotherapy by 61% of responders, 22% used the same device to crush other nonchemotherapy medications. The majority of responders disposed of medication waste with regular garbage or poured the remainder down the sink. Caregiver survey responses demonstrated that personal safeguards were not routinely utilized by pediatric caregivers while handling oral chemotherapy. Future educational efforts should be directed to improve caregiver understanding related to the use of protective equipment, designation of supplies for use with chemotherapy agents, and safe disposal.

  5. Selection of chemotherapy for non-small cell lung cancer is facilitated by new therapeutic strategies

    PubMed Central

    Wang, Zhehai

    2014-01-01

    Nowadays, advanced non-small cell lung cancer is still an incurable disease. Recent researches have led to considerable progress in the treatment of non-small cell lung cancer. This article reviews the main studies on chemotherapy on non-small cell lung cancer and discusses the new therapeutic strategies available to date. Stable disease (SD) is necessary in chemotherapy for tumor. The proportion of population with responders or SD basically maintained similar regardless of regimens. The overall survival after chemotherapy for patients with SD was lower than patients with responders, and higher than patients with progressive disease. Greater benefits could be achieved in patients with effective induction chemotherapy using chemotherapeutic agents for maintenance therapy, whereas the benefits were relatively small for patients with SD. It has been found that epidermal growth factor receptor (EGFR) mutation status had certain correlation with the efficacy of chemotherapy. First-line chemotherapy has shown advantages in effective rate and progression free survival on EGFR mutant. EGFR mutation produced significant effects on the efficacy of postoperative adjuvant chemotherapy. Patients with EGFR mutation had a higher effective rate than wild-type EGFR patients, and patients with responders had a greater benefit in progression free survival from maintenance therapy. However, it is still necessary to carry out more careful and deeper studies and analyses on traditional cytotoxic chemotherapy, to further optimize cytotoxic chemotherapy and to use molecular targeted agents with different mechanisms. PMID:25550891

  6. Hypersensitivity to antineoplastic agents.

    PubMed

    Castells, M C

    2008-01-01

    The need to offer first line therapy for primary and recurrent cancers has spurred the clinical development of rapid desensitizations for chemotherapy and monoclonal antibodies. Rapid desensitizations allow patients to be treated with medications to which they have presented with hypersensitivity reactions (HSRs), including anaphylaxis. Rapid desensitization achieves temporary tolerization to full therapeutic doses by slow administration of incremental doses of the drug inducing the HSR. Protocols are available for most chemotherapy agents, including taxanes, platins, doxorubicin, monoclonal antibodies, and others. Candidate patients include those who present with type I HSRs, mast cell/IgE dependent, including anaphylaxis, and non-IgE mediated HSRs, during the chemotherapy infusion or shortly after. Idiosyncratic reactions, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis are not amenable to rapid desensitization. The recommendation for rapid desensitization can only be made by allergy and immunology specialists and can only be performed in settings with one-to-one nurse-patient care and where resuscitation personnel and resources are readily available. Repeated desensitizations can be safely performed in outpatient settings with similar conditions, which allow cancer patients to remain in clinical studies. We have generated a universal 12-step protocol that was applied to 413 cases of intravenous and intraperitoneal rapid desensitizations using taxanes, platins, liposomal doxorubicin, doxorubicin, rituximab, and other chemotherapy drugs. Under this protocol all patients were able to complete their target dose, and 94% of the patients had limited or no reactions. No deaths or codes were reported, indicating that the procedure was safe and effective in delivering first line chemotherapy drugs.

  7. Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting.

    PubMed

    Aziz, Fahad

    2012-07-01

    Chemotherapy can be a life-prolonging treatment for many cancer patients, but it is often associated with profound nausea and vomiting that is so distressing that patients may delay or decline treatment to avoid these side effects. The discovery of several NK1 receptor antagonists is a big revolution to dealt this problem. NK1 receptor antagonists prevent both acute and delayed chemotherapy-induced nausea and vomiting (CINV). These agents act centrally at NK-1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy. By controlling nausea and vomiting, these agents help improve patients' daily living and their ability to complete multiple cycles of chemotherapy. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.

  8. Etravirine: a good option for concomitant use with chemotherapy for Hodgkin's lymphoma.

    PubMed

    Kurz, Mario; Stoeckle, Marcel; Krasniqi, Fatime; Battegay, Manuel; Marzolini, Catia

    2015-03-01

    The treatment of malignancies in HIV patients is challenged by the issue of drug-drug interactions between antiretroviral therapy and antineoplastic agents. While protease inhibitors have been shown to increase the incidence and severity of cancer therapy-related side effects, the impact of other antiretroviral agents on the tolerability and response to chemotherapy is less well documented. We report the successful use of an etravirine-based regimen in a patient treated with BEACOPP chemotherapy for advanced Hodgkin's lymphoma. Etravirine constitutes a valuable option for concomitant use with chemotherapy due to its moderate inducing effect on drug metabolising enzymes.

  9. Medication Safety of Five Oral Chemotherapies: A Proactive Risk Assessment

    PubMed Central

    Weingart, Saul N.; Spencer, Justin; Buia, Stephanie; Duncombe, Deborah; Singh, Prabhjyot; Gadkari, Mrinalini; Connor, Maureen

    2011-01-01

    Purpose: Oral chemotherapies represent an emerging risk area in ambulatory oncology practice. To examine the hazards associated with five oral chemotherapies, we performed a proactive risk assessment. Methods: We convened interdisciplinary teams and conducted failure mode and effects analyses (FMEAs) for five oral chemotherapy agents: capecitabine, imatinib, temozolomide, 6-mercaptopurine, and an investigational agent. This involved the creation of process maps for each medication, identification of failure modes, selection of high-risk failure modes, and development of recommendations to mitigate these risks. We analyzed the number of steps and types of failure modes and compared this information across the study drugs. Results: Key vulnerabilities include patient education about drug handling and adverse effects, prescription writing, patient self-administration and medication adherence, and failure to monitor and manage toxicities. Many of these failure modes were common across the five oral chemotherapies, suggesting the presence of common targets for improvement. Streamlining the FMEA itself may promote the dissemination of this method. Conclusion: Each stage of the medication process poses risks to the safe use of oral chemotherapies. FMEAs may identify opportunities to improve medication safety and reduce the risk of patient harm. PMID:21532801

  10. Relevance of high-dose chemotherapy in solid tumours.

    PubMed

    Nieboer, P; de Vries, E G E; Mulder, N H; van der Graaf, W T A

    2005-05-01

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a variety of tumour types showed good response rates. Nowadays, several phase 3 studies are available especially in metastatic and high-risk breast cancer patients. The high expectations of high-dose chemotherapy did not come true. This review analyses results of randomised studies and comments on the discrepancy between findings in patients versus those in tissue culture. Potential factors involved are the presence of tumour stem cells with different characteristics from more mature tumour cells, limitations in drug escalation in the clinic, transplant mortality, trial design and tumour cell contamination of the haematopoietic stem cell transplant. Maturation of the results from recent studies indicating a more modest benefit in, e.g., adjuvant breast cancer balanced versus long-term side effects will ultimately determine the role of high-dose chemotherapy in certain solid tumours. In case of well-defined indications for high-dose chemotherapy, further selection of patients based on patient and tumour characteristics as well as the introduction of new agents will most likely play a role.

  11. Chemotherapy following radium-223 dichloride treatment in ALSYMPCA.

    PubMed

    Sartor, Oliver; Hoskin, Peter; Coleman, Robert E; Nilsson, Sten; Vogelzang, Nicholas J; Petrenciuc, Oana; Staudacher, Karin; Thuresson, Marcus; Parker, Christopher

    2016-07-01

    Radium-223 prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium-223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium-223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium-223. In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium-223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed. Overall, 142 radium-223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium-223, 72% placebo) and mitoxantrone (16% radium-223, 20% placebo). The majority of patients (61% radium-223, 58% placebo) had received prior docetaxel. Radium-223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium-223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3-4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium-223 versus placebo patients. Median overall survivals from start of chemotherapy were 16

  12. Implementation of the American Society of Clinical Oncology and Oncology Nursing Society chemotherapy safety standards.

    PubMed

    Vioral, Anna N; Kennihan, Heather K

    2012-12-01

    Chemotherapy involves an intricate, high-risk, multidisciplinary process of prescribing, dispensing, and administering complex multimedication regimens with narrow therapeutic indices. Chemotherapeutic agents also require safe-handling precautions for patients and healthcare providers. In addition, a number of chemotherapy and targeted therapies have expanded to nononcology populations. This complexity demands standardization of chemotherapy practice for all healthcare providers to ensure safe outcomes. This article describes one organization's multidisciplinary effort to standardize chemotherapy practice according to the American Society of Clinical Oncology and Oncology Nursing Society's 31 safety standards for chemotherapy administration. The article also describes how the organization integrated and developed standards of practice using interdisciplinary approaches. The educational processes used during implementation and the lessons learned are discussed to assist healthcare providers involved in standardizing chemotherapy administration. The article equips healthcare professionals with a multidisciplinary process for high-quality clinical standards of practice that may reduce errors and ensure safety.

  13. ATP-binding cassette transporters in tumor endothelial cells and resistance to metronomic chemotherapy.

    PubMed

    Hida, Kyoko; Kikuchi, Hiroshi; Maishi, Nako; Hida, Yasuhiro

    2017-02-16

    Drug resistance is a major problem in anticancer therapy. ATP-binding cassette (ABC) transporters have a role in the multidrug resistance. A new regimen of chemotherapy has been proposed, called "metronomic chemotherapy". Metronomic chemotherapy is the frequent, regular administration of drug doses designed to maintain low, but active, concentrations of chemotherapeutic drugs over prolonged periods of time, without causing serious toxicities. Metronomic chemotherapy regimens were developed to optimize the antitumor efficacy of agents that target the tumor vasculature instead of tumor cells, and to reduce toxicity of antineoplastic drugs [1]. Nevertheless, recent studies revealed that ABC transporters are expressed at a higher level in the endothelium in the tumor. To avoid resistance to metronomic anti-angiogenic chemotherapy, ABC transporter inhibition of tumor endothelial cells may be a promising strategy. In this mini-review, we discuss the possible mechanism of resistance to metronomic chemotherapy from the viewpoint of tumor endothelial cell biology, focusing on ABC transporters.

  14. Cytotoxic Chemotherapy Tooth Ache Following Chemotherapy: a Rare Case Report

    PubMed Central

    Kuzekanani, Maryam; Haghani, Jahangir

    2012-01-01

    Currently, localized pulpalgia is listed as a rare manifestation of chemotherapy treatments in patients with malignant tumors. The neuropathy originated from neurotoxicity of anticancer drugs is usually described as a diffuse jaw pain or numbness in orofacial structures. This article reports localized tooth pain as a possible outcome of administrating high dosage chemotherapy drugs particularly in the last cycles of application. PMID:25628837

  15. Why chemotherapy can fail?

    PubMed

    Król, M; Pawłowski, K M; Majchrzak, K; Szyszko, K; Motyl, T

    2010-01-01

    There are many reasons that lead to failure of cancer chemotherapy. Cancer has the ability to become resistant to many different types of drugs. Increased efflux of drug, enhanced repair/increased tolerance to DNA damage, high antiapoptotic potential, decreased permeability and enzymatic deactivation allow cancer cell survive the chemotherapy. Treatment can lead to the death of most tumor cells (drug-sensitive), but some of them (drug-resistant) survive and grow again. These tumor cells may arise from stem cells. There are many studies describing human experiments with multidrug resistance, especially in breast cancer. Unfortunately, studies of canine or feline ABC super family members are not as extensive as in human or mice and they are limited to several papers describing PGP in mammary cancer, cutaneous mast cell tumors and lymphoma. Multidrug resistance is one of the most significant problems in oncology today. The involvement of many different, not fully recognized, mechanisms in multidrug resistance of cancer cells makes the development of effective methods of therapy very difficult. Understanding the mechanisms of drug resistance in cancer cells may improve the results of treatment. This review article provides a synopsis of all aspects that refer to cancer cell resistance to antitumor drugs.

  16. Efflux pump-mediated resistance in chemotherapy.

    PubMed

    Ughachukwu, Po; Unekwe, Pc

    2012-07-01

    Efflux pump mechanisms perform important physiological functions such as prevention of toxin absorption from the gastrointestinal tract, elimination of bile from the hepatocytes, effective functioning of the blood-brain barrier and placental barrier, and renal excretion of drugs. They exist in all living cells, but those in the bacterial and mammalian cells are more important to the clinician and pharmacologist, as they constitute an important cause of antimicrobial drug resistance, which contributes to treatment failure, high medical bills, and increased mortality / morbidity. This review was aimed at highlighting the role of efflux pump mechanisms in microbial resistance to chemotherapeutic agents. It was also aimed to elucidate their structure and mechanisms of action so as to integrate the efflux pump mechanisms in the design and development of novel antimicrobial agents. Findings from previous studies and research on this subject assessed through Google search, Pubmed, Hinari websites, as well as standard textbooks on chemotherapy, provided the needed information in the process of this review. Efflux pump inhibitors are promising strategies for preventing and reverting efflux-mediated resistance to chemotherapeutic agents. They are usually employed as adjuncts in antimicrobial and cancer chemotherapy. Toxicity, more common with the older-generation inhibitors such as verapamil and reserpine, constitutes the greatest impediment to their clinical applications. No efflux pump inhibitor has been approved for routine clinical use, as a result of doubtful clinical efficacy and unacceptably high incidence of adverse effects, particularly inhibition of the P-450 drug metabolizing enzyme. At present, their applications are mainly restricted to epidemiological studies. Nonetheless, the search for efficacious and tolerable efflux pump inhibitors continues because of the potential benefits. There is a need to consider efflux pump substrate selectivity in the design and

  17. Recent advances in the chemotherapy of herpes virus infections.

    PubMed

    Eşanu, V

    1981-01-01

    The main categories of antiherpes agents presently used in chemotherapy area reviewed according to the phase of virus replication affected : 1) virus adsorption (adamantane, nonionic surfactants) ; 2) eclipse (interferon) ; 3) virion maturation (nucleoside and nucleotide analogues and phosphonic acid derivatives). Mention is also made of other compounds--different synthetic organic derivatives, photodynamic dyes, metal ions, boric acid, hormones, antibiotics, other natural products (extracts from marine algae, propolis, garlic)--with promising antiviral properties. The difficulties and prospects of viral chemotherapy research are briefly discussed.

  18. [Prophylaxis of chemotherapy-induced vomiting and nausea].

    PubMed

    Tóth, Judit; Szántó, János

    2008-12-01

    Chemotherapy-induced vomiting and nausea is the most common adverse event of anticancer therapy. In different guide-lines (MASCC, NCCN, ESMO and ASCO) antiemetic prophylaxis is directed toward the emetogenic potential of the chemotherapy and the type of vomiting and nausea. Chemotherapeutic agents are classified into four emetic risk groups: high, moderate, low, and minimal. Steroids, dexamethasone, metoclopramide, cannabinoids, benzodiazepines, 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) and a new group of antiemetics, the neurokinin1 receptor antagonists are used to prevent anticipatory, acute and delayed vomiting and nausea. This paper examines evidence-based recommendations for optimal use of antiemetics.

  19. Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma.

    PubMed

    Thomas, Alissa A; Abrey, Lauren E; Terziev, Robert; Raizer, Jeffrey; Martinez, Nina L; Forsyth, Peter; Paleologos, Nina; Matasar, Matthew; Sauter, Craig S; Moskowitz, Craig; Nimer, Stephen D; DeAngelis, Lisa M; Kaley, Thomas; Grimm, Sean; Louis, David N; Cairncross, J Gregory; Panageas, Katherine S; Briggs, Samuel; Faivre, Geraldine; Mohile, Nimish A; Mehta, Jayesh; Jonsson, Philip; Chakravarty, Debyani; Gao, Jianjiong; Schultz, Nikolaus; Brennan, Cameron W; Huse, Jason T; Omuro, Antonio

    2017-10-01

    Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy. Patients with AO/AOA received 6 cycles of TMZ (200 mg/m2 × 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m2/day × 3 days, then busulfan 3.2 mg/kg/day × 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing. Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors. TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odg_msk_2017, accessed 6 January 2017. NCT00588523.

  20. Chemotherapy-induced peripheral neuropathy: an update on the current understanding.

    PubMed

    Addington, James; Freimer, Miriam

    2016-01-01

    Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects.

  1. Chemotherapy-induced peripheral neuropathy: an update on the current understanding

    PubMed Central

    Addington, James; Freimer, Miriam

    2016-01-01

    Chemotherapy-induced peripheral neuropathy is a common side effect of selected chemotherapeutic agents. Previous work has suggested that patients often under report the symptoms of chemotherapy-induced peripheral neuropathy and physicians fail to recognize the presence of such symptoms in a timely fashion. The precise pathophysiology that underlies chemotherapy-induced peripheral neuropathy, in both the acute and the chronic phase, remains complex and appears to be medication specific. Recent work has begun to demonstrate and further clarify potential pathophysiological processes that predispose and, ultimately, lead to the development of chemotherapy-induced peripheral neuropathy. There is increasing evidence that the pathway to neuropathy varies with each agent. With a clearer understanding of how these agents affect the peripheral nervous system, more targeted treatments can be developed in order to optimize treatment and prevent long-term side effects. PMID:27408692

  2. Novel agents for advanced pancreatic cancer

    PubMed Central

    Akinleye, Akintunde; Iragavarapu, Chaitanya; Furqan, Muhammad; Cang, Shundong; Liu, Delong

    2015-01-01

    Pancreatic cancer is relatively insensitive to conventional chemotherapy. Therefore, novel agents targeting dysregulated pathways (MAPK/ERK, EGFR, TGF-β, HEDGEHOG, NOTCH, IGF, PARP, PI3K/AKT, RAS, and Src) are being explored in clinical trials as monotherapy or in combination with cytotoxic chemotherapy. This review summarizes the most recent advances with the targeted therapies in the treatment of patients with advanced pancreatic cancer. PMID:26369833

  3. Chemotherapy and molecular targeting therapy for recurrent cervical cancer

    PubMed Central

    Tsuda, Naotake; Watari, Hidemichi; Ushijima, Kimio

    2016-01-01

    For patients with primary stage ⅣB, persistent, or recurrent cervical cancer, chemotherapy remains the standard treatment, although it is neither curative nor associated with long-term disease control. In this review, we summarized the history of treatment of recurrent cervical cancer, and the current recommendation for chemotherapy and molecular targeted therapy. Eligible articles were identified by a search of the MEDLINE bibliographical database for the period up to November 30, 2014. The search strategy included the following any or all of the keywords: “uterine cervical cancer”, “chemotherapy”, and “targeted therapies”. Since cisplatin every 21 days was considered as the historical standard treatment for recurrent cervical cancer, subsequent trials have evaluated and demonstrated activity for other agents including paclitaxel, gemcitabine, topotecan and vinorelbine among others. Accordingly, promising agents were incorporated into phase Ⅲ trials. To examine the best agent to combine with cisplatin, several landmark phase Ⅲ clinical trials were conducted by Gynecologic Oncology Group (GOG) and Japan Clinical Oncology Group (JCOG). Through, GOG204 and JCOG0505, paclitaxel/cisplatin (TP) and paclitaxel/carboplatin (TC) are now considered to be the recommended therapies for recurrent cervical cancer patients. However, the prognosis of patients who are already resistant to chemotherapy, are very poor. Therefore new therapeutic strategies are urgently required. Molecular targeted therapy will be the most hopeful candidate of these strategies. From the results of GOG240, bevacizumab combined with TP reached its primary endpoint of improving overall survival (OS). Although, the prognosis for recurrent cervical cancer patients is still poor, the results of GOG240 shed light on the usefulness of molecular target agents to chemotherapy in cancer patients. Recurrent cervical cancer is generally considered incurable and current chemotherapy regiments

  4. Palliative chemotherapy: oxymoron or misunderstanding?

    PubMed

    Roeland, E J; LeBlanc, T W

    2016-03-21

    Oncologists routinely prescribe chemotherapy for patients with advanced cancer. This practice is sometimes misunderstood by palliative care clinicians, yet data clearly show that chemotherapy can be a powerful palliative intervention when applied appropriately. Clarity regarding the term "palliative chemotherapy" is needed: it is chemotherapy given in the non-curative setting to optimize symptom control, improve quality of life, and sometimes to improve survival. Unfortunately, oncologists lack adequate tools to predict which patients will benefit. In a study recently published in BMC Palliative Care, Creutzfeldt et al. presented an innovative approach to advancing the science in this area: using patient reported outcomes to predict responses to palliative chemotherapy. With further research, investigators may be able to develop predictive models for use at the bedside to inform clinical decision-making about the risks and benefits of treatment. In the meantime, oncologists and palliative care clinicians must work together to reduce the use of "end-of-life chemotherapy"-chemotherapy given close to death, which does not improve longevity or symptom control-while optimizing the use of chemotherapy that has true palliative benefits for patients.

  5. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  6. A history of cancer chemotherapy.

    PubMed

    DeVita, Vincent T; Chu, Edward

    2008-11-01

    The use of chemotherapy to treat cancer began at the start of the 20th century with attempts to narrow the universe of chemicals that might affect the disease by developing methods to screen chemicals using transplantable tumors in rodents. It was, however, four World War II-related programs, and the effects of drugs that evolved from them, that provided the impetus to establish in 1955 the national drug development effort known as the Cancer Chemotherapy National Service Center. The ability of combination chemotherapy to cure acute childhood leukemia and advanced Hodgkin's disease in the 1960s and early 1970s overcame the prevailing pessimism about the ability of drugs to cure advanced cancers, facilitated the study of adjuvant chemotherapy, and helped foster the national cancer program. Today, chemotherapy has changed as important molecular abnormalities are being used to screen for potential new drugs as well as for targeted treatments.

  7. Adjuvant chemotherapy for advanced endometrial cancer.

    PubMed

    Galaal, Khadra; Al Moundhri, Mansour; Bryant, Andrew; Lopes, Alberto D; Lawrie, Theresa A

    2014-05-15

    Approximately 13% of women diagnosed with endometrial cancer present with advanced stage disease (International Federation of Gynecology and Obstetrics (FIGO) stage III/IV). The standard treatment of advanced endometrial cancer consists of cytoreductive surgery followed by radiation therapy, or chemotherapy, or both. There is currently little agreement about which adjuvant treatment is the safest and most effective. To evaluate the effectiveness and safety of adjuvant chemotherapy compared with radiotherapy or chemoradiation, and to determine which chemotherapy agents are most effective in women presenting with advanced endometrial cancer (FIGO stage III/IV). We searched the Cochrane Gynaecological Cancer Collaborative Review Group's Trial Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 10 2013), MEDLINE and EMBASE up to November 2013. Also we searched electronic clinical trial registries for ongoing trials. Randomised controlled trials (RCTs) of adjuvant chemotherapy compared with radiotherapy or chemoradiation in women with FIGO stage III and IV endometrial cancer. Two review authors selected trials, extracted data, and assessed trials for risk of bias. Where necessary, we contacted trial investigators for relevant, unpublished data. We pooled data using the random-effects model in Review Manager (RevMan) software. We included four multicentre RCTs involving 1269 women with primary FIGO stage III/IV endometrial cancer. We considered the trials to be at low to moderate risk of bias. All participants received primary cytoreductive surgery. Two trials, evaluating 620 women (83% stage III, 17% stage IV), compared adjuvant chemotherapy with adjuvant radiotherapy; one trial evaluating 552 women (88% stage III, 12% stage IV) compared two chemotherapy regimens (cisplatin/doxorubicin/paclitaxel (CDP) versus cisplatin/doxorubicin (CD) treatment) in women who had all undergone adjuvant radiotherapy; and one trial contributed no data

  8. Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk, locally advanced/inflammatory, and metastatic breast cancer.

    PubMed

    VanderWalde, A; Ye, W; Frankel, P; Asuncion, D; Leong, L; Luu, T; Morgan, R; Twardowski, P; Koczywas, M; Pezner, R; Paz, I B; Margolin, K; Wong, J; Doroshow, J H; Forman, S; Shibata, S; Somlo, G

    2012-08-01

    Patients with high-risk locally advanced/inflammatory and oligometastatic (≤3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor-positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials.

  9. Understanding resistance to combination chemotherapy.

    PubMed

    Pritchard, Justin R; Lauffenburger, Douglas A; Hemann, Michael T

    2012-10-01

    The current clinical application of combination chemotherapy is guided by a historically successful set of practices that were developed by basic and clinical researchers 50-60 years ago. Thus, in order to understand how emerging approaches to drug development might aid the creation of new therapeutic combinations, it is critical to understand the defining principles underlying classic combination therapy and the original experimental rationales behind them. One such principle is that the use of combination therapies with independent mechanisms of action can minimize the evolution of drug resistance. Another is that in order to kill sufficient cancer cells to cure a patient, multiple drugs must be delivered at their maximum tolerated dose - a condition that allows for enhanced cancer cell killing with manageable toxicity. In light of these models, we aim to explore recent genomic evidence underlying the mechanisms of resistance to the combination regimens constructed on these principles. Interestingly, we find that emerging genomic evidence contradicts some of the rationales of early practitioners in developing commonly used drug regimens. However, we also find that the addition of recent targeted therapies has yet to change the current principles underlying the construction of anti-cancer combinatorial regimens, nor have they made substantial inroads into the treatment of most cancers. We suggest that emerging systems/network biology approaches have an immense opportunity to impact the rational development of successful drug regimens. Specifically, by examining drug combinations in multivariate ways, next generation combination therapies can be constructed with a clear understanding of how mechanisms of resistance to multi-drug regimens differ from single agent resistance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Chemotherapy-induced nausea and vomiting: pathophysiology and therapeutic principles.

    PubMed

    Bayo, Juan; Fonseca, Paula J; Hernando, Susana; Servitja, S; Calvo, A; Falagan, S; García, Estefanía; González, Iria; de Miguel, María José; Pérez, Quionia; Milena, Ana; Ruiz, Antonio; Barnadas, Agustí

    2012-06-01

    Chemotherapy-induced nausea and vomiting (CINV) is a major determinant of quality of life in cancer patients. In addition, the perceptions that oncology professionals have about CINV quite often do not coincide with reality. Antineoplastic agents and their combinations can be categorised according to their emetogenic level, and this categorisation is helpful for classifying the severity of CINV and treating it. All CINV treatment guidelines emphasise the need to administer prophylaxis to patients who receive highly or moderately emetogenic chemotherapy. With the introduction of NK1 receptor antagonists, the control of acute and delayed CINV after highly or moderately emetogenic chemotherapy schedules has improved in the great majority of patients. NK1 receptor antagonists have been demonstrated to improve the control of CINV in all risk subgroups of patients.

  11. A randomized trial of minoxidil in chemotherapy-induced alopecia.

    PubMed

    Duvic, M; Lemak, N A; Valero, V; Hymes, S R; Farmer, K L; Hortobagyi, G N; Trancik, R J; Bandstra, B A; Compton, L D

    1996-07-01

    Hair loss is a side effect of many chemotherapeutic agents, and patients have even refused possibly palliative or lifesaving drugs because they could not accept temporary or prolonged baldness. Topical minoxidil has been shown to be effective for androgenetic alopecia and alopecia areata. Our purpose was to investigate the value and safety of minoxidil in chemotherapy-induced hair loss. Twenty-two women who were facing adjuvant chemotherapy after breast surgery were registered in a protocol that used a 2% minoxidil topical solution or a placebo in a randomized double-blind trial. There was a statistically significant difference (favoring minoxidil) in the interval from maximal hair loss to first regrowth. Thus the period of baldness was shortened (mean, 50.2 days) in the minoxidil group. Minoxidil decreased the duration of alopecia caused by chemotherapy. There were no significant side effects.

  12. Chemotherapy-induced peripheral neuropathy - epidemiology and pathogenesis.

    PubMed

    Iżycki, Dariusz; Niezgoda, Adam; Kaźmierczak, Maciej; Nowak-Markwitz, Ewa

    2016-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most important neurologic complications experienced by patients receiving chemotherapy. The neuropathy often interferes with daily activities and exercise leading to severe impairment of the patient's quality of life (QoL). The evolution of most CIPNs is characterized by a gradual onset of signs/symptoms, beginning in the lower limbs and advancing proximally into a bilateral stocking and glove distribution. Patients often complain of numbness, tingling and pain in the affected areas. The symptoms become aggravated with repeated cycles of chemotherapy. When the offending agent is withheld, the symptoms generally abate, but relief is not guaranteed. The consequences of delay or discontinuation of treatment may affect overall patient survival.

  13. Portal venous gas following chemotherapy for colorectal cancer liver metastasis.

    PubMed

    Zalinski, S; Scatton, O; Jacqmin, S; Tacher, V; Brézault, C; Soubrane, O

    2009-05-01

    The standard of care for patients with colorectal liver metastases is a combination of chemotherapy and surgery. New chemotherapy regimens with biologic agents (cetuximab, bevacizumab) have been shown to increase tumor response rates. Although this might be beneficial and this is an expected endpoint, it should be noted that patients with synchronous colorectal and liver metastases are at risk of septic complications. We recently encountered a case of hepatic portal venous gas after two cycles of chemotherapy in a patient with right colon cancer liver metastases. Complete necrosis of the liver metastasis subsequently turned into a liver abscess, which fistulized in the right portal vein. Infection of the necrotized metastasis was thought to be promoted by the colic tumor. Although this is a dramatic situation, it does not contraindicate a curative surgical resection.

  14. Chemotherapy-induced peripheral neuropathy: Current status and progress.

    PubMed

    Brewer, Jamie R; Morrison, Gladys; Dolan, M Eileen; Fleming, Gini F

    2016-01-01

    As there are increasing numbers of cancer survivors, more attention is being paid to the long term unwanted effects patients may experience as a result of their treatment and the impact these side effects can have on their quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common long-term toxicities from chemotherapy. In this review we will briefly review the clinical presentation, evaluation and management of chemotherapy-induced peripheral neuropathy, with a focus on CIPN related to platinum and taxane agents. We will then discuss current clinical models of peripheral neuropathy and ongoing research to better understand CIPN and develop potential treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Viruses, chemotherapy and immunity.

    PubMed

    Koziel, M J; Walker, B D

    1992-01-01

    An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression. The interdependence of host immunity with antiviral efficacy is underscored by the increased antiviral drug resistance in persons with advanced degrees of chronic immunosuppression, related to the higher level of viral replication and viraemia which occurs in the absence of an effective host immune response. Further definition of the precise mechanisms of these interactions should facilitate the rational design of antiviral agents and immunomodulatory therapies to improve treatment of viral infections.

  16. Major contributions towards finding a cure for cancer through chemotherapy: a historical review.

    PubMed

    Masood, Imran; Kiani, Maria H; Ahmad, Mahmood; Masood, Muhammed I; Sadaquat, Hadia

    2016-01-01

    The history of cancer chemotherapy is as old as cancer itself. With the increase in the complexities of cancer and the development of resistance towards existing anticancer agents, increased attention is now being paid to the advancement of chemotherapy. Some chemotherapeutic agents were discovered by accident or trial-and-error methods while others were found to be useful for neoplasia when they were being evaluated for some other purpose. Broadly, these agents have been classified as alkylating agents, antimetabolites, platinum compounds, antitumor antibiotics and natural products. Hormones and compounds interfering with hormone metabolism are widely used in cancer treatment, besides monoclonal antibodies and small molecules targeting angiogenesis. In this review an attempt is made to discuss the major breakthroughs that have shaped the course of cancer chemotherapy, helping to decrease the mortality as well as lessen the suffering of patients.

  17. The impacts of a pharmacist-managed outpatient clinic and chemotherapy-directed electronic order sets for monitoring oral chemotherapy.

    PubMed

    Battis, Brandon; Clifford, Linda; Huq, Mostaqul; Pejoro, Edrick; Mambourg, Scott

    2016-10-12

    Patients treated with oral chemotherapy appear to have less contact with the treating providers. As a result, safety, adherence, medication therapy monitoring, and timely follow-up may be compromised. The trend of treating cancer with oral chemotherapy agents is on the rise. However, standard clinical guidance is still lacking for prescribing, monitoring, patient education, and follow-up of patients on oral chemotherapy across the healthcare settings. The purpose of this project is to establish an oral chemotherapy monitoring clinic, to create drug and lab specific provider order sets for prescribing and lab monitoring, and ultimately to ensure safe and effective treatment of the veterans we serve. A collaborative agreement was reached among oncology pharmacists, a pharmacy resident, two oncologists, and a physician assistant to establish a pharmacist-managed oral chemotherapy monitoring clinic at the VA Sierra Nevada Healthcare System. Drug-specific electronic order sets for prescribing and lab monitoring were created for initiating new drug therapy and prescription renewal. The order sets were created to be provider-centric, minimizing clicks needed to order necessary medications and lab monitoring. A standard progress note template was developed for documenting interventions made by the clinic. Patients new to an oral chemotherapy regimen were first counseled by an oncology pharmacist. The patients were then enrolled into the oral chemotherapy monitoring clinic for subsequent follow up and pharmacist interventions. Further, patients lacking monitoring or missing provider appointments were captured through a Clinical Dashboard developed by the US Department of Veterans Affairs (VA) Regional Office (VISN21) using SQL Server Reporting Services. Between September 2014 and April 2015, a total of 68 patients on different oral chemotherapy agents were enrolled into the clinic. Out of the 68 patients enrolled into the oral chemotherapy monitoring clinic, 31 patients (45

  18. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN)

    PubMed Central

    Han, Yaqin; Smith, Maree T.

    2013-01-01

    Chemotherapy induced peripheral neuropathy (CIPN) is a type of neuropathic pain that is a major dose-limiting side-effect of potentially curative cancer chemotherapy treatment regimens that develops in a “stocking and glove” distribution. When pain is severe, a change to less effective chemotherapy agents may be required, or patients may choose to discontinue treatment. Medications used to alleviate CIPN often lack efficacy and/or have unacceptable side-effects. Hence the unmet medical need for novel analgesics for relief of this painful condition has driven establishment of rodent models of CIPN. New insights on the pathobiology of CIPN gained using these models are discussed in this review. These include mitochondrial dysfunction and oxidative stress that are implicated as key mechanisms in the development of CIPN. Associated structural changes in peripheral nerves include neuronopathy, axonopathy and/or myelinopathy, especially intra-epidermal nerve fiber (IENF) degeneration. In patients with CIPN, loss of heat sensitivity is a hallmark symptom due to preferential damage to myelinated primary afferent sensory nerve fibers in the presence or absence of demyelination. The pathobiology of CIPN is complex as cancer chemotherapy treatment regimens frequently involve drug combinations. Adding to this complexity, there are also subtle differences in the pathobiological consequences of commonly used cancer chemotherapy drugs, viz platinum compounds, taxanes, vincristine, bortezomib, thalidomide and ixabepilone, on peripheral nerves. PMID:24385965

  19. Pharmacokinetics of metronomic chemotherapy: a neglected but crucial aspect.

    PubMed

    Bocci, Guido; Kerbel, Robert S

    2016-11-01

    Metronomic chemotherapy describes the close, regular administration of chemotherapy drugs at less-toxic doses over prolonged periods of time. In 2015, the results of randomized phase III clinical trials demonstrated encouraging, albeit limited, efficacy benefits of metronomic chemotherapy regimens administered as adjuvant maintenance therapy for the treatment of breast cancer, or as maintenance therapy in combination with an antiangiogenic agent for metastatic colorectal cancer. Owing to the investigational nature of this approach, metronomic chemotherapy regimens are highly empirical in terms of the optimal dose and schedule for the drugs administered; therefore, greater knowledge of the pharmacokinetics of metronomic chemotherapy is critical to the future success of this treatment strategy. Unfortunately, such preclinical and clinical pharmacokinetic studies are rare. Herein, we present situations in which active drug concentrations have been achieved with metronomic schedules, and discuss their associated pharmacokinetic parameters. We summarize examples from the limited number of clinical studies in order to illustrate the importance of assessing such pharmacokinetic parameters, and discuss the influence this information can have on improving efficacy and reducing toxicity.

  20. Chemotherapy for Soft Tissue Sarcomas

    MedlinePlus

    ... most commonly used drugs are ifosfamide (Ifex ® ) and doxorubicin (Adriamycin ® ). When ifosfamide is used, the drug mesna ... a shortened name such as: MAID (mesna, Adriamycin [doxorubicin], ifosfamide, and dacarbazine). Chemotherapy drugs kill cancer cells ...

  1. Bone marrow osteoblast vulnerability to chemotherapy

    PubMed Central

    Gencheva, Marieta; Hare, Ian; Kurian, Susan; Fortney, Jim; Piktel, Debbie; Wysolmerski, Robert; Gibson, Laura F.

    2013-01-01

    Osteoblasts are a major component of the bone marrow microenvironment which provide support for hematopoietic cell development. Functional disruption of any element of the bone marrow niche, including osteoblasts, can potentially impair hematopoiesis. We have studied the effect of two widely used drugs with different mechanisms of action, etoposide (VP16) and melphalan, on murine osteoblasts at distinct stages of maturation. VP16 and melphalan delayed maturation of preosteoblasts and altered CXCL12 protein levels, a key regulator of hematopoietic cell homing to the bone marrow. Sublethal concentrations of VP16 and melphalan also decreased the levels of several transcripts which contribute to the composition of the extracellular matrix (ECM) including osteopontin (OPN), osteocalcin (OCN) and collagen 1A1 (Col1a1). The impact of chemotherapy on message and protein levels for some targets was not always aligned, suggesting differential responses at the transcription and translation or protein stability levels. Since one of the main functions of a mature osteoblast is to synthesize ECM of a defined composition, disruption of the ratio of its components may be one mechanism by which chemotherapy affects the ability of osteoblasts to support hematopoietic recovery coincident with altered marrow architecture. Collectively, these observations suggest that the osteoblast compartment of the marrow hematopoietic niche is vulnerable to functional dysregulation by damage imposed by agents frequently used in clinical settings. Understanding the mechanistic underpinning of chemotherapy-induced changes on the hematopoietic support capacity of the marrow microenvironment may contribute to improved strategies to optimize patient recovery post-transplantation. PMID:23551534

  2. Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer.

    PubMed

    Sternberg, Cora N; Donat, S Machele; Bellmunt, Joaquim; Millikan, Randall E; Stadler, Walter; De Mulder, Pieter; Sherif, Amir; von der Maase, Hans; Tsukamoto, Taiji; Soloway, Mark S

    2007-01-01

    To determine the optimal use of chemotherapy in the neoadjuvant, adjuvant, and metastatic setting in patients with advanced urothelial cell carcinoma, a consensus conference was convened by the World Health Organization (WHO) and the Société Internationale d'Urologie (SIU) to critically review the published literature on chemotherapy for patients with locally advanced bladder cancer. This article reports the development of international guidelines for the treatment of patients with locally advanced bladder cancer with neoadjuvant and adjuvant chemotherapy. Bladder preservation is also discussed, as is chemotherapy for patients with metastatic urothelial cancer. The conference panel consisted of 10 medical oncologists and urologists from 3 continents who are experts in this field and who reviewed the English-language literature through October 2004. Relevant English-language literature was identified with the use of Medline; additional cited works not detected on the initial search regarding neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and chemotherapy for patients with metastatic urothelial cancer were reviewed. Evidence-based recommendations for diagnosis and management of the disease were made with reference to a 4-point scale. Results of the authors' deliberations are presented as a consensus document. Meta-analysis of randomized trials on cisplatin-containing combination neoadjuvant chemotherapy revealed a 5% difference in favor of neoadjuvant chemotherapy. No randomized trials have yet compared survival with transurethral resection of bladder tumor alone versus cystectomy for the management of patients with muscle-invasive disease. Collaborative international adjuvant chemotherapy trials are needed to assist researchers in assessing the true value of adjuvant chemotherapy. Systemic cisplatin-based combination chemotherapy is the only current modality that has been shown in phase 3 trials to improve survival in responsive patients

  3. Personalized chemotherapy of lung cancer: What the radiologist should know.

    PubMed

    Ferretti, G R; Reymond, E; Delouche, A; Sakhri, L; Jankowski, A; Moro-Sibilot, D; Lantuejoul, S; Toffart, A C

    2016-03-01

    Lung cancer is the leading cause of deaths due to cancer in France. More than half of lung cancers are discovered at an advanced-stage. New anticancer treatment strategies (i.e., the so-called personalized or targeted therapy) have recently been introduced and validated for non-small-cell lung cancer (NSCLC), in addition to or in association with standard chemotherapy. Personalized therapy includes tyrosine kinase inhibitors (TKIs), antiangiogenic treatments and immunotherapy. Because these treatments may be responsible for atypical thoracic adverse effects and responses as compared to standard chemotherapy, RECIST 1.1 criteria may be inadequate to evaluate the responses to these agents. The goal of this article was to review personalized treatment strategies for NSCLC, to consider the therapy-specific responses and thoracic complications induced by these new therapeutic agents and finally to discuss future directions for the personalized assessment of tumor response.

  4. Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.

    PubMed

    Shankar, Abhishek; Roy, Shubham; Malik, Abhidha; Julka, P K; Rath, G K

    2015-01-01

    The supportive care of patients receiving antineoplastic treatment has dramatically improved over the past few years and development of effective measures to prevent nausea and vomiting after chemotherapy serves as one of the most important examples of this progress. A patient who starts cancer treatment with chemotherapy lists chemotherapy-induced nausea and vomiting as among their greatest fears. Inadequately controlled emesis impairs functional activity and quality of life, increases the use of health care resources, and may occasionally compromise adherence to treatment. New insights into the pathophysiology of chemotherapy-induced nausea and vomiting, a better understanding of the risk factors for these effects, and the availability of new antiemetic agents have all contributed to substantial improvements in emetic control. This review focuses on current understanding of chemotherapy-induced nausea and vomiting and the status of pharmacological interventions for their prevention and treatment.

  5. Ceramide in chemotherapy of tumors.

    PubMed

    Dimanche-Boitrel, Marie-Thérèse; Rebillard, Amélie; Gulbins, Erich

    2011-09-01

    It is well known that tumor formation arises from the imbalance between cell death and proliferation. For many years, cancer research has engaged an important part of its efforts to find new therapeutic strategies based on cell death induction. One of the predominant ways to kill tumor cells is to trigger apoptosis by chemotherapy. However tumor responsiveness to chemotherapy is dependent on different biological factors including cancer types, genetics and pharmacogenetics. Although molecular mechanisms involved in chemotherapy-induced apoptosis are diverse and depend on cell-type and drugs used, a common pathway leading to tumor cell death has been shown to implicate the generation of a simple cellular sphingolipid, ceramide. Ceramide is released by the activity of neutral or acidic sphingomyelinases or de novo synthesis during treatment with chemotherapy. This review in particular focuses on enzymes involved in chemotherapy-induced cell death such as neutral or acidic sphingomyelinases and ceramide synthases, the role of ceramide in cellular effects of chemotherapy at the plasma membrane or the mitochondria and the induction of cell death by ceramide. It also includes recent advances on novel patented sphingolipid compounds and cancer therapeutic strategies based on ceramide release.

  6. Tackling pancreatic cancer with metronomic chemotherapy.

    PubMed

    Romiti, Adriana; Falcone, Rosa; Roberto, Michela; Marchetti, Paolo

    2017-05-28

    Pancreatic tumours, the majority of which arise from the exocrine pancreas, have recently shown an increasing incidence in western countries. Over the past few years more and more new selective molecules directed against specific cellular targets have become available for cancer therapy, leading to significant improvements. However, despite such advances in therapy, prognosis of pancreatic cancer remains disappointing. Metronomic chemotherapy (MCT), which consists in the administration of continuous, low-dose anticancer drugs, has demonstrated the ability to suppress tumour growth. Thus, it may provide an additional therapeutic opportunity for counteracting the progression of the tumour. Here we discuss evidence arising from preclinical and clinical studies regarding the use of MCT in pancreatic cancer. Good results have generally been achieved in preclinical studies, particularly when MCT was combined with standard dose chemotherapy or antinflammatory, antiangiogenic and immunostimolatory agents. The few available clinical experiences, which mainly refer to retrospective data, have reported good tolerability though mild activity of metronomic schedules. Further studies are therefore awaited to confirm both preclinical findings and the preliminary clinical data.

  7. Chemotherapy of squamous cell cancer of the head and neck.

    PubMed

    Gill, P G; Hains, J D; Iyer, P; Rozenbilds, J G; Ahmad, A; Abbott, R L; David, D J; Ward, G G; Brown, M W; Harvey, N D

    1983-05-14

    Forty patients with advanced squamous cell cancer of the head and neck were treated with methotrexate, cisplatin, and bleomycin. Major regression of disease occurred in 69%; 30% of patients achieved complete remission. Fifteen patients received chemotherapy as the initial treatment, followed by either radiotherapy or surgery or both. Subsequent therapy was not prejudiced by this approach. The results demonstrate the marked sensitivity of these tumors to these three agents, and the need for further assessment of their use in optimal patient care.

  8. Stability issues of parenteral chemotherapy drugs.

    PubMed

    de Lemos, Mário L; Hamata, Linda

    2007-03-01

    The pharmacist often needs to have all the information required to prepare and to assign an expiry date for parenteral products of antineoplastic agents. The pharmaceutical manufacturers usually provide data on how to prepare their products and the associated physicochemical stability. Standard reference texts also provide additional summary information of other primary data. However, it is not uncommon to find knowledge gaps in this area. Hence, additional extrapolation and consensus on interpretation is often needed to address issues not covered by data from the pharmaceutical manufacturers, standard reference texts, or official guidelines. Some of the key issues have been identified in our recent development of a chemotherapy preparation and stability chart. These include use of data from different brands, expiry date of original vial and final products, risk of contamination, infusion volume and stability, multi-day home-use products, syringe preparations, and products to be used immediately. Potential approaches to address these common issues are described in this article.

  9. Oncolytic herpes simplex virus vectors and chemotherapy: are combinatorial strategies more effective for cancer?

    PubMed Central

    Kanai, Ryuichi; Wakimoto, Hiroaki; Cheema, Tooba; Rabkin, Samuel D

    2010-01-01

    Despite aggressive treatments, including chemotherapy and radiotherapy, cancers often recur owing to resistance to conventional therapies. Oncolytic viruses such as oncolytic herpes simplex virus (oHSV) represent an exciting biological approach to cancer therapy. A range of viral mutations has been engineered into HSV to engender oncolytic activity. While oHSV as a single agent has been tested in a number of cancer clinical trials, preclinical studies have demonstrated enhanced efficacy when it is combined with cytotoxic anticancer drugs. Among the strategies that will be discussed in this article are combinations with standard-of-care chemotherapeutics, expression of prodrug-activating enzymes to enhance chemotherapy and small-molecule inhibitors. The combination of oHSV and chemotherapy can achieve much more efficient cancer cell killing than either single agent alone, often through synergistic interactions. This can be clinically important not just for improving efficacy but also for permitting lower and less toxic chemotherapeutic doses. The viral mutations in an oHSV vector often determine the favorability of its interactions with chemotherapy, just as different cancer cells, due to genetic alterations, vary in their response to chemotherapy. As chemotherapeutics are often the standard of care, combining them with an investigational new drug, such as oHSV, is clinically easier than combining multiple novel agents. As has become clear for most cancer therapies, multimodal treatments are usually more effective. In this article, we will discuss the recent progress of these combinatorial strategies between virotherapy and chemotherapy and future directions. PMID:20373873

  10. Greater risks of chemotherapy toxicity in elderly patients with cancer.

    PubMed

    Repetto, Lazzaro

    2003-01-01

    Complications of cytotoxic chemotherapy are more common in older patients (65 years of age and older) with cancer than in younger patients, and the occurrence of myelosuppression, mucositis, cardiodepression, peripheral neuropathy, and central neurotoxicity can complicate treatment. Age-related physiologic changes that can increase the toxicity of chemotherapy are decreased stem-cell reserves, decreased ability to repair cell damage, progressive loss of body protein, and accumulation of body fat. A decline in organ function can alter the pharmacokinetics of many of the commonly used chemotherapeutic agents in some elderly patients, making toxicity less predictable. Comorbidities increase the risk of toxicity through their effects on the body. Furthermore, the drugs used to treat comorbidities may interact with chemotherapeutic drugs, potentially increasing toxicity in elderly patients. Prospective trials in older patients with lymphoma or solid tumors have found that age is a risk factor for chemotherapy-induced neutropenia and its complications. Anemia may be present because of the disease or its treatment, and, if left uncorrected, it can alter drug activity and increase toxicity. Being able to predict which elderly patients are at greater risk of toxicity on the basis of pretreatment factors would be valuable, and there is a need for prospective trials to determine regimen- and patient-specific prognostic factors. Effective management of the toxicity associated with chemotherapy with appropriate supportive care is crucial, especially in the elderly population, to give them the best chance of cure and survival, or to provide palliation. For example, management of neutropenic complications with colony-stimulating factors makes treatment with standard-dose chemotherapy possible, which can lead to better outcomes. A better understanding of drug activity and toxicity in older patients is necessary for developing guidelines for safe and effective treatment. Few

  11. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... Orange Parkinson’s Awareness Month Were you exposed to herbicides during service and have Parkinson’s disease? You may ...

  12. Chemotherapy vs tamoxifen in platinum-resistant ovarian cancer: a phase III, randomised, multicentre trial (Ovaresist).

    PubMed

    Lindemann, Kristina; Gibbs, Emma; Åvall-Lundqvist, Elisabeth; dePont Christensen, Rene; Woie, Kathrine; Kalling, Marten; Auranen, Annika; Grenman, Seija; Hoegberg, Thomas; Rosenberg, Per; Skeie-Jensen, Tone; Hjerpe, Elisabet; Dørum, Anne; Gebski, Val; Kristensen, Gunnar

    2017-02-14

    Chemotherapy in platinum-resistant ovarian cancer (PROC) aims for palliation and prolonging of progression-free survival (PFS). This study compares Health-related Quality of Life (HRQoL) and efficacy between single-agent chemotherapy and tamoxifen in PROC. Patients with PROC were randomised (2 : 1) to chemotherapy (weekly paclitaxel 80 mg m(-2) or four weekly pegylated liposomal doxorubicin 40 mg m(-2)) or tamoxifen 40 mg daily. The primary end point was HRQoL. Secondary end points were PFS by RECIST and overall survival (OS). Between March 2002 and December 2007, 156 and 82 patients were randomised to chemotherapy and tamoxifen, respectively. In the chemotherapy arm, a significantly larger proportion of patients experienced a worsening in their social functioning. There was no difference in the proportion of patients experiencing improvement of gastrointestinal symptoms. Median PFS on tamoxifen was 8.3 weeks (95% CI, 8.0-10.4) compared with 12.7 weeks (95% CI, 9.0-16.3) on chemotherapy (HR, 1.54; 95% CI, 1.16-2.05; log-rank P=0.003). There was no difference in OS between the treatment arms. Patients on chemotherapy had longer PFS but experienced more toxicity and poorer HRQoL compared with tamoxifen. Control over gastrointestinal symptoms was not better on chemotherapy. These data are important for patient counselling and highlight the need to incorporate HRQoL end points in studies of PROC.

  13. Review on adjuvant chemotherapy for rectal cancer - why do treatment guidelines differ so much?

    PubMed

    Poulsen, Laurids Ø; Qvortrup, Camilla; Pfeiffer, Per; Yilmaz, Mette; Falkmer, Ursula; Sorbye, Halfdan

    2015-04-01

    The use of postoperative adjuvant chemotherapy is controversial for rectal adenocarcinoma. Both international and national guidelines display a great span varying from recommending no adjuvant chemotherapy at all, over single drug 5-fluororuacil (5-FU), to combinations of 5-FU/oxaliplatin. A review of the literature was made identifying 24 randomized controlled trials on adjuvant treatment of rectal cancer based on about 10 000 patients. The trials were subdivided into a number of clinically relevant subgroups. As regards patients treated with preoperative (chemo) radiotherapy, four randomized studies were found where use of adjuvant chemotherapy showed no benefit in survival. Three trials were found in which a subset of patients received preoperative (chemo) radiotherapy. Two of these trials showed a statistically significant benefit of adjuvant chemotherapy. Twenty trials were identified in which the patients did not receive preoperative (chemo) radiotherapy, including five Asian studies in which a statistically significant benefit from adjuvant chemotherapy was reported. Most of the data found did not support the use of postoperative adjuvant chemotherapy for patients already treated with preoperative (chemo) radiotherapy. For patients not treated preoperatively, several studies support the use of single agent 5-FU chemotherapy. Treatment guidelines seem to differ according to if preoperative chemoradiation is considered of importance for use of adjuvant chemotherapy and if adjuvant colon cancer studies are considered transferrable to rectal cancer patients regardless of the molecular differences.

  14. Genome-wide discovery of loci influencing chemotherapy cytotoxicity.

    PubMed

    Watters, James W; Kraja, Aldi; Meucci, Melissa A; Province, Michael A; McLeod, Howard L

    2004-08-10

    Little is known about the heritability of chemotherapy activity or the identity of genes that may enable the individualization of cancer chemotherapy. Although numerous genes are likely to influence chemotherapy response, current candidate gene-based pharmacogenetics approaches require a priori knowledge and the selection of a small number of candidate genes for hypothesis testing. In this study, an ex vivo familial genetics strategy using lymphoblastoid cells derived from Centre d'Etude du Polymorphisme Humain reference pedigrees was used to discover genetic determinants of chemotherapy cytotoxicity. Cytotoxicity to the mechanistically distinct chemotherapy agents 5-fluorouracil and docetaxel were shown to be heritable traits, with heritability values ranging from 0.26 to 0.65 for 5-fluorouracil and 0.21 to 0.70 for docetaxel, varying with dose. Genome-wide linkage analysis was also used to map a quantitative trait locus influencing the cellular effects of 5-fluorouracil to chromosome 9q13-q22 [logarithm of odds (LOD) = 3.44], and two quantitative trait loci influencing the cellular effects of docetaxel to chromosomes 5q11-21 (LOD = 2.21) and 9q13-q22 (LOD = 2.73). Finally, 5-fluorouracil and docetaxel were shown to cause apoptotic cell death involving caspase-3 cleavage in Centre d'Etude du Polymorphisme Humain lymphoblastoid cells. This study identifies genomic regions likely to harbor genes important for chemotherapy cytotoxicity using genome-wide linkage analysis in human pedigrees and provides a widely applicable strategy for pharmacogenomic discovery without the requirement for a priori candidate gene selection.

  15. Progress in systemic chemotherapy of primary breast cancer: an overview.

    PubMed

    Hortobagyi, G N

    2001-01-01

    Substantial progress has been made in the multidisciplinary management of primary breast cancer during the last 30 years. Adjuvant chemotherapy has been shown to significantly reduce the annual risk of cancer recurrence and mortality, and these effects persist even 15 years after diagnosis. Combination chemotherapy is superior to single-agent therapy and anthracycline-containing regimens. Those that combine an anthracycline with 5-fluorouracil and cyclophosphamide are more effective than regimens without an anthracycline. Six cycles of a single regimen appear to provide optimal benefit. Dose reductions below the standard range are associated with inferior results. Dose increases that require growth factor or hematopoietic stem cell support are under investigation; at this time, the existing results provide no compelling reason to use this strategy outside a clinical trial. Regimens using fixed crossover designs with two non-cross-resistant regimens are being evaluated. The addition of a taxane to anthracycline-containing regimens is currently under intense scrutiny, and preliminary analysis of the first three clinical trials has shown encouraging, albeit not compelling, results. For patients with estrogen receptor-positive breast cancer, the sequential administration of chemotherapy and 5 years of tamoxifen therapy provides additive benefits. No compelling evidence exists to combine ovarian ablation with chemotherapy. Most side effects and toxic effects are self-limited, although premature menopause requires monitoring and preventive interventions to preserve bone mineral density. The small risk of acute leukemia is of concern, and additional research to develop safer regimens is clearly indicated. The overall effect of optimal local/regional treatment combined with an anthracycline-containing adjuvant chemotherapy and a taxane (and, for patients with estrogen receptor-positive tumors, 5 years of tamoxifen therapy) is a greater than 50% reduction in annual risks of

  16. Discovery and Delivery of Synergistic Chemotherapy Drug Combinations to Tumors

    NASA Astrophysics Data System (ADS)

    Camacho, Kathryn Militar

    applied to various agents. Findings from our research can potentially widen the therapeutic window of chemotherapy combinations by emphasizing investigations of optimal drug ratios rather than maximum drug doses and by identifying appropriate nanoparticles for their delivery. Application of these concepts can ultimately help capture the full therapeutic potential of combination regimens.

  17. Risk-reduction and treatment of chemotherapy-induced peripheral neuropathy.

    PubMed

    Bakogeorgos, Marios; Georgoulias, Vassilis

    2017-09-11

    Chemotherapy-induced peripheral neuropathy (CIPN), a common adverse effect of several chemotherapeutic agents, has a significant impact on quality of life and may even compromise treatment efficacy, requiring chemotherapy dose reduction or discontinuation. CIPN is predominantly related with sensory rather than motor symptoms and the most common related cytotoxic agents are platinum compounds, taxanes and vinca alkaloids. CIPN symptoms may resolve after treatment cessation, but they can also be permanent and continue for years. Areas covered: We present an overview of CIPN pathophysiology, clinical assessment, prevention and treatment identified through a Pubmed search. Expert commentary: No substantial progress has been made in the last few years within the field of prevention and/or treatment of CIPN, in spite of remarkable efforts. Continuous research could expand our knowledge about chemotherapeutic-specific neuropathic pathways and eventually lead to the conception of innovative and targeted agents for the prevention and/or treatment of this debilitating chemotherapy adverse effect.

  18. Chemotherapy and novel therapeutics before radical prostatectomy for high-risk clinically localized prostate cancer.

    PubMed

    Cha, Eugene K; Eastham, James A

    2015-05-01

    Although both surgery and radiation are potential curative options for men with clinically localized prostate cancer, a significant proportion of men with high-risk and locally advanced disease will demonstrate biochemical and potentially clinical progression of their disease. Neoadjuvant systemic therapy before radical prostatectomy (RP) is a logical strategy to improve treatment outcomes for men with clinically localized high-risk prostate cancer. Furthermore, delivery of chemotherapy and other systemic agents before RP affords an opportunity to explore the efficacy of these agents with pathologic end points. Neoadjuvant chemotherapy, primarily with docetaxel (with or without androgen deprivation therapy), has demonstrated feasibility and safety in men undergoing RP, but no study to date has established the efficacy of neoadjuvant chemotherapy or neoadjuvant chemohormonal therapies. Other novel agents, such as those targeting the vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, clusterin, and immunomodulatory therapeutics, are currently under investigation.

  19. Myeloablative chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors: results of Korean Society of Pediatric Neuro-Oncology (KSPNO) S-053 study.

    PubMed

    Baek, Hee Jo; Park, Hyeon Jin; Sung, Ki Woong; Lee, Soo Hyun; Han, Jung Woo; Koh, Kyung Nam; Im, Ho Joon; Kang, Hyoung Jin; Park, Kyung Duk

    2013-09-01

    The present study evaluated the feasibility and effectiveness of myeloablative high-dose chemotherapy and autologous stem cell transplantation in patients with relapsed or progressed central nervous system germ cell tumors (CNS-GCTs). Eleven patients with non-germinomatous germ cell tumors and nine patients with germinomas were enrolled. Patients received between two and eight cycles of conventional chemotherapy prior to HDCT/autoSCT with or without radiotherapy. Overall, 16 patients proceeded to the first HDCT/autoSCT, and nine proceeded to the second HDCT/autoSCT. CTE (carboplatin-thiotepa-etoposide) and cyclophosphamide-melphalan (CM) regimens were used for the first and second HDCT, respectively. Toxicities during HDCT/autoSCT were acceptable, and there were no treatment-related deaths. Twelve patients experienced relapse or progression; however, four patients with germinomas remain alive after subsequent RT. Therefore, a total of 12 patients (four NGGCTs and eight germinomas) remain alive with a median follow-up of 47 months (range 22-90) after relapse or progression. The probability of 3-year overall survival was 59.1 ± 11.2 % (36.4 ± 14.5 % for NGGCTs vs. 88.9 ± 10.5 % for germinomas, P = 0.028). RT, particularly craniospinal RT, was associated with a better tumor response prior to HDCT/autoSCT and a better final outcome. In conclusion, HDCT/autoSCT was feasible, and survival rates were encouraging. Further study with a larger cohort of patients is needed to elucidate the role of HDCT/autoSCT in the treatment of relapsed or progressed CNS-GCTs.

  20. Randomized Phase II trial of two high-dose chemotherapy regimens with stem cell transplantation for the treatment of advanced ovarian cancer in first remission or chemosensitive relapse: a Southwest Oncology Group study.

    PubMed

    Stiff, Patrick J; Shpall, Elizabeth J; Liu, P Y; Wilczynski, Sharon P; Callander, Natalie S; Scudder, Sidney A; Jazieh, Abdul-Rahman; Samlowski, Wolfram; McCoy, Jason; Alberts, David S

    2004-07-01

    To evaluate response rates, progression-free survival (PFS), overall survival (OS), and toxicity of two high-dose chemotherapy regimens with stem cell rescue used to treat patients with recurrent or persistent stage III/IV ovarian cancer, with the goal of taking one forward into a Phase III comparison with conventional therapy. Patients under 65 with clinically or pathologically persistent disease after initial chemotherapy or those relapsing >6 months after a complete remission (CR) were randomized to CMC carboplatin (1500 mg/m(2)), mitoxantrone (75 mg/m(2)), and cyclophosphamide (120 mg/kg)], or CTC: [cisplatin (165 mg/m(2)), thiotepa (600 mg/m(2)), and cyclophosphamide (5625 mg/m(2))] with stem cell rescue. Of 67 randomized, the 32 and 26 eligible in the CMC and CTC arms were matched including age (median 49), maximum tumor diameter, and disease status at transplant. Low-risk disease (maximum diameter disease

  1. [Update on antimicrobial chemotherapy].

    PubMed

    Cattoir, V; Daurel, C

    2010-03-01

    There is a constant need for new antibacterial agents because of the unavoidable development of bacterial resistance that follows the introduction of antibiotics in clinical practice. As observed in many fields, innovation generally comes by series. For instance, a wide variety of broad-spectrum antibacterial agents became available between the 1970s and the 1990s, such as cephalosporins, penicillin/beta-lactamase inhibitor combinations, carbapenems, and fluoroquinolones. Over the last 2 decades, the arrival of new antibacterial drugs on the market has dramatically slowed, leaving a frequent gap between isolation of resistant pathogens and effective treatment options. In fact, many pharmaceutical companies focused on the development of narrow-spectrum antibiotics targeted at multidrug-resistant Gram-positive bacteria (e.g. methicillin-resistant Staphylococcus aureus, penicillin resistant Streptococcus pneumoniae, and vancomycin-resistant Enterococcus faecium). Therefore, multidrug-resistant Gram-negative bacteria (e.g. extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Pseudomonas aeruginosa and Acinetobacter baumannii) recently emerged and rapidly spread worldwide. Even if some molecules were developed, new molecules for infections caused by these multidrug-resistant Gram-negative bacteria remain remarkably scarce compared to those for Gram-positive infections. This review summarises the major microbiological, pharmacological, and clinical properties of systemic antibiotics recently marketed in France (i.e. linezolid, daptomycin, tigecycline, ertapenem, and doripenem) as well as those of antibacterial drugs currently in development (i.e. ceftobiprole, ceftaroline, dalbavancin, telavancin, oritavancin, iclaprim, and ramoplanin) or available in other countries (i.e. garenoxacin, sitafloxacin, and temocillin).

  2. Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy

    PubMed Central

    Wennier, Sonia Tusell; Liu, Jia; McFadden, Grant

    2015-01-01

    Single agent therapies are rarely successful in treating cancer, particularly at metastatic or end stages, and survival rates with monotherapies alone are generally poor. The combination of multiple therapies to treat cancer has already driven significant improvements in the standard of care treatments for many types of cancers. The first combination treatments exploited for cancer therapy involved the use of several cytotoxic chemotherapy agents. Later, with the development of more targeted agents, the use of novel, less toxic drugs, in combination with the more classic cytotoxic drugs has proven advantageous for certain cancer types. Recently, the combination of oncolytic virotherapy with chemotherapy has shown that the use of these two therapies with very distinct anti-tumor mechanisms may also lead to synergistic interactions that ultimately result in increased therapeutic effects not achievable by either therapy alone. The mechanisms of synergy between oncolytic viruses (OVs) and chemotherapeutic agents are just starting to be elucidated. It is evident, however, that the success of these OV-drug combinations depends greatly on the particular O V, the drug(s) selected, and the cancer type targeted. This review summarizes the different OV-drug combinations investigated to date, including the use of second generation armed OVs, which have been studied with the specific purpose of generating synergistic interactions with particular chemotherapy agents. The known mechanisms of synergy between these OV-drug combinations are also summarized. The importance of further investigating these mechanisms of synergy will be critical in order to maximize the therapeutic efficacy of OV-drug combination therapies in the future. PMID:21740354

  3. Bugs and drugs: oncolytic virotherapy in combination with chemotherapy.

    PubMed

    Wennier, Sonia Tusell; Liu, Jia; McFadden, Grant

    2012-07-01

    Single agent therapies are rarely successful in treating cancer, particularly at metastatic or end stages, and survival rates with monotherapies alone are generally poor. The combination of multiple therapies to treat cancer has already driven significant improvements in the standard of care treatments for many types of cancers. The first combination treatments exploited for cancer therapy involved the use of several cytotoxic chemotherapy agents. Later, with the development of more targeted agents, the use of novel, less toxic drugs, in combination with the more classic cytotoxic drugs has proven advantageous for certain cancer types. Recently, the combination of oncolytic virotherapy with chemotherapy has shown that the use of these two therapies with very distinct anti-tumor mechanisms may also lead to synergistic interactions that ultimately result in increased therapeutic effects not achievable by either therapy alone. The mechanisms of synergy between oncolytic viruses (OVs) and chemotherapeutic agents are just starting to be elucidated. It is evident, however, that the success of these OV-drug combinations depends greatly on the particular OV, the drug(s) selected, and the cancer type targeted. This review summarizes the different OV-drug combinations investigated to date, including the use of second generation armed OVs, which have been studied with the specific purpose of generating synergistic interactions with particular chemotherapy agents. The known mechanisms of synergy between these OV-drug combinations are also summarized. The importance of further investigating these mechanisms of synergy will be critical in order to maximize the therapeutic efficacy of OV-drug combination therapies in the future.

  4. Practical considerations in ovarian cancer chemotherapy

    PubMed Central

    Cristea, Mihaela; Han, Ernest; Salmon, Lennie; Morgan, Robert J.

    2010-01-01

    Epithelial ovarian cancer remains the most lethal gynecologic malignancy despite advances in treatment. The standard management generally involves a combination of surgical tumor debulking and chemotherapy. Over the decades, chemotherapy for ovarian cancer has evolved and currently involves a combination of intravenous platinum and taxane chemotherapy. Over the past decade, three randomized phase III trials have been reported, and all have demonstrated a significant survival advantage for intraperitoneal compared with intravenous chemotherapy. However, there are potential barriers and controversies related to the administration of intraperitoneal chemotherapy in ovarian cancer patients. In this review, we discuss the evolution and current management considerations of chemotherapy for the treatment of epithelial ovarian cancer. PMID:21789133

  5. Surgical technology and pharmacology of hyperthermic perioperative chemotherapy

    PubMed Central

    Van der Speeten, Kurt

    2016-01-01

    Although cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC) have not been shown to be effective by themselves, as a combined treatment they are now standard of care for peritoneal metastases from appendiceal cancer and from colorectal cancer as well as peritoneal mesothelioma. The timing of the HIPEC in relation to the CRS is crucial in that the HIPEC is to destroy minimal residual disease that remains following the CRS and prevent microscopic tumor emboli within the abdomen and pelvis from implanting within the resection site, within fibrinous clot, or within blood clot. Proper selection of chemotherapy agents is crucial to the long-term benefit of CRS and HIPEC. One must consider the response expected with the cancer chemotherapy agent, its area under the curve (AUC) ratio indicating the amount of dose intensity within the peritoneal space, and the drug retention within the peritoneal space for a prolonged exposure. Hyperthermia will augment the cytotoxicity of the cancer chemotherapy agents and improve drug penetration. Irrigation techniques should not be overlooked as an important means of reducing the cancer cell burden within the abdomen and pelvis. Multiple technologies for HIPEC exist and these have advantages and disadvantages. The techniques vary from a totally open technique with a vapor barrier over the open abdominal space to a totally closed technique whereby the HIPEC is administered at the completion of the surgical procedure. The open techniques depend on a table-mounted retractor for suspension of the skin edges allowing a reservoir to occur within the abdomen and pelvis. There are nearly a dozen commercially available hyperthermia pumps, all of which seem to perform adequately for HIPEC although there is a variable degree of convenience and documentation of the HIPEC procedure. As the management of peritoneal metastases has progressed over three decades, early cases are now seen in which a laparoscopic CRS and HIPEC

  6. Sphingolipids and response to chemotherapy.

    PubMed

    Dimanche-Boitrel, Marie-Thérèse; Rebillard, Amélie

    2013-01-01

    Chemotherapy is frequently used to treat primary or metastatic cancers, but intrinsic or acquired drug resistance limits its efficiency. Sphingolipids are important regulators of various cellular processes including proliferation, apoptosis, differentiation, angiogenesis, stress, and inflammatory responses which are linked to various aspects of cancer, like tumor growth, neoangiogenesis, and response to chemotherapy. Ceramide, the central molecule of sphingolipid metabolism, generally mediates antiproliferative and proapoptotic functions, whereas sphingosine-1-phosphate and other derivatives have opposing effects. Among the variety of enzymes that control ceramide generation, acid or neutral sphingomyelinases and ceramide synthases are important targets to allow killing of cancer cells by chemotherapeutic drugs. On the contrary, glucosylceramide synthase, ceramidase, and sphingosine kinase are other targets driving cancer cell resistance to chemotherapy. This chapter focuses on ceramide-based mechanisms leading to cancer therapy sensitization or resistance which could have some impacts on the development of novel cancer therapeutic strategies.

  7. New Insights into Potential Prevention and Management Options for Chemotherapy-Induced Peripheral Neuropathy

    PubMed Central

    Schloss, Janet; Colosimo, Maree; Vitetta, Luis

    2016-01-01

    Objective: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain are frequent side effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention, and treatment of these neurological complications be implemented. Methods: A consideration was undertaken of the current options regarding protective and treatment interventions for patients undergoing chemotherapy with neurotoxic chemotherapy agent or experience with CIPN. Current knowledge on the mechanism of action has also been identified. The following databases PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, CINAHL, CNKI, and Google Scholar were searched for relevant article retrieval. Results: A range of pharmaceutical, nutraceutical, and herbal medicine treatments were identified that either showed efficacy or had some evidence of efficacy. Duloxetine was the most effective pharmaceutical agent for the treatment of CIPN. Vitamin E demonstrated potential for the prevention of cisplatin-IPN. Intravenous glutathione for oxaliplatin, Vitamin B6 for both oxaliplatin and cisplatin, and omega 3 fatty acids for paclitaxel have shown protection for CIPN. Acetyl-L-carnitine may provide some relief as a treatment option. Acupuncture may be of benefit for some patients and Gosha-jinki-gan may be of benefit for protection from adverse effects of oxaliplatin induced peripheral neuropathy. Conclusions: Clinicians and researchers acknowledge that there are numerous challenges involved in understanding, preventing, and treating peripheral neuropathy caused by chemotherapeutic agents. New insights into mechanisms of action from chemotherapy agents may facilitate the development of novel preventative and treatment options, thereby enabling medical staff to better support patients by reducing this

  8. Mobilization of peripheral blood progenitor cells by chemotherapy and granulocyte-macrophage colony-stimulating factor for hematologic support after high-dose intensification for breast cancer.

    PubMed

    Elias, A D; Ayash, L; Anderson, K C; Hunt, M; Wheeler, C; Schwartz, G; Tepler, I; Mazanet, R; Lynch, C; Pap, S

    1992-06-01

    High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous

  9. Early use of chemotherapy in metastatic prostate cancer.

    PubMed

    Markowski, Mark C; Carducci, Michael A

    2016-10-03

    Since 2010, five new antineoplastic therapies have been FDA approved for the treatment of metastatic prostate cancer. With additional treatment options, questions arose about the optimal sequence of these agents. Until recently, chemotherapy has been deferred until later in the disease course in favor of next-generation androgen deprivation therapy. Prior to the development of abiraterone acetate and enzalutamide, clinical trials were opened investigating the combination of chemotherapy with androgen deprivation therapy in patients with metastatic hormone-sensitive disease. With the development of new oral therapies used to treat castration-resistant disease, these trials were largely forgotten or felt to be obsolete. Recently, two trials have been reported showing an overall survival benefit of the early use of chemotherapy in patients with hormone-naive prostate cancer, changing the treatment paradigm for metastatic disease. Here we review the history of chemotherapy in treating prostate cancer and the emerging evidence favoring its use as first-line therapy against metastatic hormone-sensitive disease.

  10. Prophylaxis for mucositis induced by ambulatory chemotherapy: systematic review.

    PubMed

    Manzi, Natália de Melo; Silveira, Renata Cristina de Campos Pereira; dos Reis, Paula Elaine Diniz

    2016-04-01

    The aim of this study was to perform a systematic review of clinical trials covering interventions used as prophylaxis for oral mucositis induced by ambulatory antineoplastic chemotherapy. Oral mucositis in patients undergoing chemotherapy is a side effect that can impact the quality of treatment and can interfere with eating and therapeutic adherence. Quantitative systematic review. Relevant databases were searched, from January 2002-July 2013, by using the combination of the keywords mucositis, stomatitis, neoplasms, antineoplastic agents, drug therapy, prevention and control and chemotherapy. Two researchers independently read the titles and abstracts from every cross-reference. The quality of the included studies was analysed by the Jadad Scale and the Cochrane Collaboration Risk of Bias Tool. Data were extracted from the selected studies with a data collection form developed specifically for this purpose. Of the 23 controlled clinical trials that were identified in this study, five articles evaluated the use of oral cryotherapy to prevent oral mucositis and three studies analysed the prophylactic use of glutamine. Interventions of protocols for oral care, palifermin, allopurinol and chlorhexidine were evaluated by two articles each. Interventions of zinc sulphate, amifostine, chewing gum, sucralfate, recombination human intestinal trefoil factor, kefir and vitamin E were evaluated by one article each. There is strong evidence that cryotherapy can prevent oral mucositis arising from ambulatory treatment with 5-flurouracil chemotherapy. Other interventions, although showing positive results in preventing oral mucositis, require further study to confirm their conclusions. © 2015 John Wiley & Sons Ltd.

  11. Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trial.

    PubMed

    Lissoni, P; Chilelli, M; Villa, S; Cerizza, L; Tancini, G

    2003-08-01

    Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms.

  12. Chemotherapy curable malignancies and cancer stem cells: a biological review and hypothesis.

    PubMed

    Savage, Philip

    2016-11-21

    Cytotoxic chemotherapy brings routine cures to only a small select group of metastatic malignancies comprising gestational trophoblast tumours, germ cell tumours, acute leukemia, Hodgkin's disease, high grade lymphomas and some of the rare childhood malignancies. We have previously postulated that the extreme sensitivity to chemotherapy for these malignancies is linked to the on-going high levels of apoptotic sensitivity that is naturally linked with the unique genetic events of nuclear fusion, meiosis, VDJ recombination, somatic hypermutation, and gastrulation that have occurred within the cells of origin of these malignancies. In this review we will examine the cancer stem cell/cancer cell relationship of each of the chemotherapy curable malignancies and how this relationship impacts on the resultant biology and pro-apoptotic sensitivity of the varying cancer cell types. In contrast to the common epithelial cancers, in each of the chemotherapy curable malignancies there are no conventional hierarchical cancer stem cells. However cells with cancer stem like qualities can arise stochastically from within the general tumour cell population. These stochastic stem cells acquire a degree of resistance to DNA damaging agents but also retain much of the key characteristics of the cancer cells from which they develop. We would argue that the balance between the acquired resistance of the stochastic cancer stem cell and the inherent chemotherapy sensitivity of parent tumour cell determines the overall chemotherapy curability of each diagnosis. The cancer stem cells in the chemotherapy curable malignancies appear to have two key biological differences from those of the more common chemotherapy incurable malignancies. The first difference is that the conventional hierarchical pattern of cancer stem cells is absent in each of the chemotherapy curable malignancies. The other key difference, we suggest, is that the stochastic stem cells in the chemotherapy curable malignancies

  13. Chemotherapy of enterobiasis (oxyuriasis).

    PubMed

    St Georgiev, V

    2001-02-01

    Enterobius vermicularis (syn. Oxyurus vermicularis), also known as pinworm or seatworm, is the causative agent of human enterobiasis (oxyuriasis). The disease is more prevalent in temperate regions and is facilitated by factors such as overcrowding in schools and family groupings, as well as inadequate personal and community hygiene. Although the infection is more likely to occur in lower socioeconomic groups, enterobiasis has been reported to affect virtually every level of the general population and especially children. In the great majority of cases, enterobiasis is asymptomatic. One common symptom is intense pruritus ani that in some patients can lead to insomnia, restlessness and irritability. Scratching may cause skin irritation, and in more serious cases, eczematous dermatitis, haemorrhage or secondary bacterial infections. Ectopic migration of E. vermicularis often results in pinworm infestation of the female genital tract often causing granulomas of the uterus, ovary and the fallopian tubes and pelvic peritoneum. Anthelmintic therapies for enterobiasis are successful and include mebendazole, albendazole and pyrantel pamoate. Mass medication of affected groups reduced symptoms rapidly, progressively and in a cost-effective way.

  14. Managing Chemotherapy Side Effects: Memory Changes

    MedlinePlus

    ... C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor ... thinking or remembering things Managing Chemotherapy Side Effects: Memory Changes Get help to remember things. Write down ...

  15. Managing Chemotherapy Side Effects: Swelling (Fluid Retention)

    MedlinePlus

    ... ational C ancer I nstitute Managing Chemotherapy Side Effects Swelling (Fluid retention) “My hands and feet were ... too much at one time. Managing Chemotherapy Side Effects: Swelling (Fluid retention) Weigh yourself. l Weigh yourself ...

  16. Advances in chemotherapy of differentiated epithelial and medullary thyroid cancers.

    PubMed

    Sherman, Steven I

    2009-05-01

    Systemic chemotherapies for advanced or metastatic thyroid carcinomas have been of only limited effectiveness. For patients with differentiated or medullary carcinomas unresponsive to conventional treatments, novel therapies are needed to improve disease outcomes. The PubMed and Google Scholar search engines were used to identify publications and peer-reviewed meeting presentations addressing chemotherapy and targeted therapy for differentiated or medullary carcinoma. Multiple novel therapies primarily targeting angiogenesis have entered clinical trials for metastatic thyroid carcinoma. Partial response rates up to 30% have been reported in single agent studies, but prolonged disease stabilization is more commonly seen. The most successful agents target the vascular endothelial growth factor receptors, with potential targets including the mutant kinases associated with papillary and medullary oncogenesis. Two drugs approved for other malignancies, sorafenib and sunitinib, have had promising preliminary results reported, and are being used selectively for patients who do not qualify for clinical trials. Randomized trials for several agents are underway that may lead to eventual drug approval for thyroid cancer. Treatment for patients with metastatic or advanced thyroid carcinoma now emphasizes clinical trial opportunities for novel agents with considerable promise. Alternative options now exist for use of tyrosine kinase inhibitors that are well tolerated and may prove worthy of regulatory approval for this disease.

  17. Tumour chemotherapy strategy based on impulse control theory.

    PubMed

    Ren, Hai-Peng; Yang, Yan; Baptista, Murilo S; Grebogi, Celso

    2017-03-06

    Chemotherapy is a widely accepted method for tumour treatment. A medical doctor usually treats patients periodically with an amount of drug according to empirical medicine guides. From the point of view of cybernetics, this procedure is an impulse control system, where the amount and frequency of drug used can be determined analytically using the impulse control theory. In this paper, the stability of a chemotherapy treatment of a tumour is analysed applying the impulse control theory. The globally stable condition for prescription of a periodic oscillatory chemotherapeutic agent is derived. The permanence of the solution of the treatment process is verified using the Lyapunov function and the comparison theorem. Finally, we provide the values for the strength and the time interval that the chemotherapeutic agent needs to be applied such that the proposed impulse chemotherapy can eliminate the tumour cells and preserve the immune cells. The results given in the paper provide an analytical formula to guide medical doctors to choose the theoretical minimum amount of drug to treat the cancer and prevent harming the patients because of over-treating.This article is part of the themed issue 'Horizons of cybernetical physics'.

  18. Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

    PubMed

    Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

    2012-03-14

    ) and the control arm (no adjuvant chemotherapy). The survival data were either entered directly in RevMan or extrapolated from Kaplan-Meier plots and then entered in RevMan. Due to expected clinical heterogeneity a random effects model was used for creating the pooled estimates of treatment efficacy. A total of 21 eligible RCTs were identified and used for meta-analysis purposes. Overall, 16,215 patients with colorectal cancer were enrolled, 9,785 being affected with rectal carcinoma. Considering patients with rectal cancer only, 4,854 cases were randomized to receive potentially curative surgery of the primary tumour plus adjuvant chemotherapy and 4,367 to receive surgery plus observation. The mean number of patients enrolled was 466 (range: 54-1,243 cases). 11 RCTs had been performed in Western countries and 10 in Japan. All trials used fluoropyrimidine-based chemotherapy (no modern drugs - such as oxaliplatin, irinotecan or biological agents - were tested).Overall survival (OS) data were available in 21 RCTs and the data available for meta-analysis regarded 9,221 patients: of these, 4854 patients were randomized to adjuvant chemotherapy (treatment arm) and 4,367 patients did not receive adjuvant chemotherapy (control arm). The meta-analysis of these RCTs showed a significant reduction in the risk of death (17%) among patients undergoing postoperative chemotherapy as compared to those undergoing observation (HR=0.83, CI: 0.76-0.91). Between-study heterogeneity was moderate (I-squared=30%) but significant (P=0.09) at the 10% alpha level.Disease-free survival (DFS) data were reported in 20 RCTs, and the data suitable for meta-analysis included 8,530 patients. Of these, 4,515 patients were randomized to postoperative chemotherapy (treatment arm) and 4,015 patients received no postoperative chemotherapy (control arm). The meta-analysis of these RCTs showed a reduction in the risk of disease recurrence (25%) among patients undergoing adjuvant chemotherapy as compared to

  19. Pharmacy program for improved handling of antineoplastic agents.

    PubMed

    Scott, S A; Schrott, D B; Loesch, G A

    1983-07-01

    A pharmacy program to improve the handling of antineoplastic drug products in a pediatric hospital is described. To correct deficiencies in the preparation and administration of cancer chemotherapy, the pharmacy department in conjunction with pediatric hematology-oncology physicians prepared a cancer chemotherapy manual. Included in the manual were (1) policies and procedures for the ordering, preparation, delivery, administration, and disposal of chemotherapy; (2) a flow sheet to facilitate ordering of daily chemotherapy doses and allow pharmacists to double-check dosage calculations of physicians; (3) drug information monographs on various antineoplastic agents used in the hospital; and (4) a reference chart containing information about the reconstitution, dilution, stability, storage, administration, and special-handling precautions for chemotherapy. Upon the recommendation of the hematology-oncology staff and with the approval of the hospital administration, the pharmacy obtained a vertical laminar-airflow hood and expanded its services to include preparation of all cancer chemotherapy for inpatients. Procedures were implemented to document delivery of chemotherapy to the nursing unit and to ensure proper acquisition and charting of chemotherapy doses given by physicians. Pharmacy involvement has improved control of the handling and administration of cancer chemotherapy in the hospital and has increased the safety of patients and hospital personnel.

  20. Optimizing Chemotherapy: Concomitant Medication Lists

    PubMed Central

    Hanigan, Marie H.; dela Cruz, Brian L.; Shord, Stacy S.; Medina, Patrick J.; Fazili, Javid; Thompson, David M.

    2013-01-01

    Identifying sources of variability in the response to cancer chemotherapy requires knowledge of all variables including concomitant medications, which can alter metabolism and pharmacokinetics of chemotherapy. This study investigated the accuracy of concomitant medication lists in the charts of cancer patients. Collated information from a questionnaire, patient interview and patient’s medical chart were used to obtain validated medication lists. Patients took an average of 4.8 prescription drugs, 1.6 non-prescription drugs and 1.6 other remedies within three days prior to chemotherapy. Medical records did not report 24% of prescription drugs, 84% of non-prescription drugs and 83% of other remedies. Electronic medical records were more complete than paper charts, but failed to report more than 75% of non-prescription drugs and other remedies. Potential drug interactions were noted. This study documents the extent and complexity of concomitant drugs taken by patients undergoing chemotherapy and the deficiencies in recording this information in medical charts. PMID:21124312

  1. Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer

    PubMed Central

    Tsuchikawa, Takahiro; Takeuchi, Shintaro; Nakamura, Toru; Shichinohe, Toshiaki; Hirano, Satoshi

    2016-01-01

    A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects. PMID:27895816

  2. Olanzapine for chemotherapy-induced nausea and vomiting: a systematic review.

    PubMed

    Hocking, Christopher M; Kichenadasse, Ganessan

    2014-04-01

    Newer drugs incorporated in prophylactic regimens for chemotherapy-induced nausea and vomiting (CINV) have resulted in significantly reduced rates of this feared complication of cytotoxic chemotherapy. However, both delayed chemotherapy-induced nausea and breakthrough CINV remain difficult areas of management and require novel treatment strategies. Recent randomized trial evidence has suggested that olanzapine, an atypical antipsychotic, may have a role in both the prevention and treatment of CINV. A systematic review was conducted to assess the efficacy of olanzapine in (a) preventing CINV in highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) and (b) the treatment of breakthrough CINV. The toxicity of olanzapine in this setting was also reviewed. MEDLINE, Embase and Cochrane Database of Systematic Reviews databases were searched to identify all randomized clinical trials (RCTs) investigating olanzapine in patients receiving chemotherapy. A total of 488 patients from three trials of CINV prophylaxis and 323 patients from three trials of breakthrough CINV were included. Regimens including olanzapine were associated with significant improvements in CINV prevention with both HEC and MEC. Single agent olanzapine for breakthrough nausea was superior to standard alternative options. Data from RCTs support the use of an olanzapine containing combination regimen as an option for CINV prophylaxis and single agent olanzapine for the treatment of breakthrough CINV. In the included trials, the short duration of olanzapine appears safe and well tolerated.

  3. Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer.

    PubMed

    Tsuchikawa, Takahiro; Takeuchi, Shintaro; Nakamura, Toru; Shichinohe, Toshiaki; Hirano, Satoshi

    2016-11-15

    A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.

  4. Update in Cancer Chemotherapy: Gastrointestinal Cancer, Cancer of the Stomach and Carcinoid Tumors

    PubMed Central

    Wright, Jane C.

    1986-01-01

    Cancer chemotherapy in the treatment of advanced gastric cancer provides only palliation with perhaps increased survival time in some patients. The primary treatment of gastric carcinomas is surgical, as this is the only hope for cure. It is estimated that 80 to 85 percent of patients with newly diagnosed cases of stomach cancer will be dead of their disease within five years. Radiation therapy alone is seldom employed, except as a palliative measure to control hemorrhage or pain. There are no data to suggest that postoperative radiation increases survival rates. Single-agent chemotherapy is of temporary palliative value in 20 to 30 percent of cases with a duration of response from three to five months. Combination chemotherapy has shown a somewhat higher response rate than single-agent therapy. In advanced gastric cancer, there is no evidence of improved long-term disease-free survival rates with any combination yet reported. The treatment of carcinoid cancer of the intestinal tract is surgical removal, as this offers the only hope of cure. Radiation therapy is of little benefit, except for moderate palliation in cases of extensive liver metasasis. Carcinoid cancers are moderately sensitive to chemotherapy. While some adjuvant chemotherapy trials suggest improvement, major survival gains remain to be demonstrated. Uncertainty as to the role of chemotherapy in the treatment of gastrointestinal cancers is probably due to lack of data. PMID:3528508

  5. Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

    PubMed

    Krukiewicz, Katarzyna; Zak, Jerzy K

    2016-05-01

    Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented.

  6. Adjuvant chemotherapy in early breast cancer.

    PubMed

    Ejlertsen, Bent

    2016-05-01

    With long-term follow-up, the DBCG 77B trial demonstrates that oral single-agent cyclophosphamide significantly reduces the risk of recurrence and mortality as compared with no systemic therapy in pre-menopausal patients with high-risk early breast cancer. DBCG 77B is the only randomised trial assessing single-agent cyclophosphamide; and a second comparison suggests that its benefits are comparable to what may be achieved by classic CMF. The lack of benefits from adding methotrexate and fluorouracil to cyclophosphamide paved the way for combining cyclophosphamide with anthracyclines and later taxanes. DBCG 89D showed an incremental benefit in DFS and OS from substituting methotrexate with epirubicin. The advantage of anthracycline-containing three-drug combinations over CMF was confirmed by others and in the individual-patient EBCTCG meta-analysis, while standard AC or EC for four cycles not was superior to classic CMF. A further reduction in breast cancer mortality appeared in the EBCTCG meta-analysis from the addition of a taxane to a standard AC, while the substitution of cycles or drugs with a taxane was not associated with a reduction in mortality. No apparent benefit was observed in an early analysis of the DBCG 82C evaluating the addition of CMF to tamoxifen in post-menopausal high-risk breast cancer patients. Apart from menopausal status, the two trials had identical selection criteria, and the differences in outcome warranted a long-term follow-up of the 82C trial. After ten years of follow-up, CMF in the DBCG 82C was associated with a significant improvement in DFS; but even with 24 years of follow-up, mortality was not significantly improved. The diversity in outcome from the 77C and the 82B trials triggered further studies. The 77B trial used classic CMF with oral cyclophospamide, while a four-weekly intravenous CMF regimen was used in the 82B and C trials, and a three-weekly CMF regimen was used in the succeeding 89B and D trials. The outcome following

  7. Mechanisms involved in the development of chemotherapy-induced neuropathy

    PubMed Central

    Boyette-Davis, Jessica A; Walters, Edgar T; Dougherty, Patrick M

    2015-01-01

    SUMMARY Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition seen in patients undergoing treatment with common agents such as vincristine, paclitaxel, oxaliplatin and bortezomib. The mechanisms of this condition are diverse, and include an array of molecular and cellular contributions. Current research implicates genetic predispositions to this condition, which then may influence cellular responses to chemotherapy. Processes found to be influenced during CIPN include increased expression of inflammatory mediators, primarily cytokines, which can create cascading effects in neurons and glia. Changes in ion channels and neurotransmission, as well as changes in intracellular signaling and structures have been implicated in CIPN. This review explores these issues and suggests considerations for future research. PMID:26087973

  8. The double-edged sword: Neurotoxicity of chemotherapy.

    PubMed

    Magge, Rajiv S; DeAngelis, Lisa M

    2015-03-01

    The number of available therapies for hematologic malignancies continues to grow at a rapid pace. Unfortunately, many of these treatments carry both central and peripheral nervous system toxicities, potentially limiting a patient's ability to tolerate a full course of treatment. Neurotoxicity with chemotherapy is common and second only to myelosuppression as a reason to limit dosing. This review addresses the neurotoxicity of newly available therapeutic agents including brentuximab vedotin and blinatumomab as well as classic ones such as methotrexate, vinca alkaloids and platinums. Although peripheral neuropathy is common with many drugs, other complications such as seizures and encephalopathy may require more immediate attention. Rapid recognition of adverse neurologic effects may lead to earlier treatment and appropriate adjustment of dosing regimens. In addition, knowledge of common toxicities may help differentiate chemotherapy-related symptoms from actual progression of cancer into the CNS.

  9. Update in Cancer Chemotherapy, Part III: Lung Cancer, Part 1

    PubMed Central

    Wright, Jane C.

    1985-01-01

    An update in cancer chemotherapy that deals with the various therapies of lung cancer is described. At present, the stage of the disease and cell type are the major factors that determine the treatment. Important differences in the biological behavior and response to treatment exist between small cell and non-small cell cancers. The small cell type is sensitive to many chemotherapeutic agents. Differences in response to chemotherapy and survival have been less among the non-small cell types. The treatment of non-small cell carcinomas including squamous cell, large cell, and adenocarcinoma are reviewed in Part I of this paper. Small cell lung cancer will be described in Part II, which will be published in a future issue of the journal. PMID:2414458

  10. Prevention of chemotherapy-induced alopecia in rodent models

    PubMed Central

    Jimenez, Joaquin J.; Roberts, Stephen M.; Mejia, Jessica; Mauro, Lucia M.; Munson, John W.; Elgart, George W.; Connelly, Elizabeth Alvarez; Chen, Qingbin; Zou, Jiangying; Goldenberg, Carlos

    2008-01-01

    Alopecia (hair loss) is experienced by thousands of cancer patients every year. Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin), taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the topisomerase inhibitor etoposide, agents that are widely used in the treatment of leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment appears to be generally effective in reliably preventing this secondary effect of chemotherapy. We observed in experiments using different rodent models that localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein response in hair follicles and effectively prevented alopecia from adriamycin, cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support the presumption that such localized hair-saving treatment does not negatively affect chemotherapy efficacy. PMID:18347939

  11. Liver toxicity during temozolomide chemotherapy caused by Chinese herbs

    PubMed Central

    2014-01-01

    Background Complementary and alternative medicine is often used by patients with malignant glioma. Although several interactions of various alternative agents with chemotherapy are known, none has been described for temozolomide so far. Case presentation We report the case of severe liver toxicity with jaundice during radiochemotherapy with temozolomide likely due to interaction with a popular Chinese herbal formula after surgery for glioblastoma. After cessation of the herbal formula as well as the chemotherapy liver enzymes slowly normalized. Due to tumor progression the patient was retreated with temozolomide for 5 cycles without toxicity. Because of further progression combination treatment of bevacizumab and irinotecan was started and again no liver toxicity was observed. Conclusions We conclude that the observed toxicity with jaundice was probably caused by an interaction of this popular Chinese formula and temozolomide. This is the first report about a relevant interaction of temozolomide and any herbal formula. PMID:24679099

  12. NTP Monograph: Developmental Effects and Pregnancy Outcomes Associated With Cancer Chemotherapy Use During Pregnancy.

    PubMed

    2013-05-01

    The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) conducted an evaluation of the developmental effects and pregnancy outcomes associated with cancer chemotherapy use during pregnancy in humans. The final NTP monograph was completed in May 2013 (available at http:// ntp.niehs.nih.gov/go/36495). The incidence of cancer during pregnancy has been reported to occur from 17 to 100 per 100,000 pregnant women. Chemotherapy is a common treatment for cancer; however, most chemotherapy agents are classified as known or suspected human teratogens. Cancer chemotherapy use during pregnancy was selected for evaluation by the NTP because of the: (1) paucity of comprehensive reviews on the pregnancy outcomes following cancer chemotherapy use during pregnancy in humans, including the integration of the developmental animal toxicology literature with the observational studies in humans, and (2) growing public interest in the developmental effects of chemotherapy on offspring exposed to cancer chemotherapy during gestation due to the expected incidence of cancer diagnosed during pregnancy as women delay pregnancy to later ages. Of the approximately 110 cancer chemotherapeutic agents currently in use, the NTP monograph includes data on 56 agents used during 1,261 pregnancies for which pregnancy outcomes were documented. Overall, the NTP evaluation found that treatment with chemotherapy for cancer appeared to be associated with: (1) a higher rate of major malformations following exposure during the first trimester compared to exposure in the second and/or third trimester; (2) an increase the rate of stillbirth following exposure in the second and/ or third trimester; abnormally low levels of amniotic fluid (primarily attributable to Trastuzumab); and (3), also data are insufficient, impaired fetal growth and myelosuppression. Treatment with chemotherapy for cancer during pregnancy did not appear to increase spontaneous preterm birth, or impair

  13. Is Routine Audiometric Evaluation Necessary in Gynaecologic Tumour Patients Undergoing Chemotherapy?

    PubMed Central

    Fasunla, Ayotunde J.; Harbeck, Nadia; Schmalfeld, Barbara; Berktold, Sabina; Böhner, Christina; Hundt, Walter; Wolf, Petra; Steinbach, Silke

    2013-01-01

    Summary Background Our objective was to assess the auditory function of gynaecological tumour patients who had received cytotoxic agents and to determine their associated risk of ototoxicity. Patients and Methods 87 patients who had undergone chemotherapy for gynaecological malignancies were investigated. Of these patients, 79% had breast cancer, and 14% ovarian cancer. All of the patients had a subjective assessment of their hearing function on a visual analogue scale. Audiometric tests were performed before and at 9 weeks, 18 weeks and 3 months after completion of chemotherapy. Results The age of the patients ranged from 32 to 71 years (mean age of 53.5 ± 10.5 years). The average subjective rating of the patients’ hearing function was 83.0 ± 17.2 before and 84.8 ± 16.9 3 months after completion of chemotherapy. No significant audiometric change at either the speech hearing frequency range (0.5–2 KHz) or high frequencies was observed in the patients after chemotherapy. There was also no significant difference in the hearing threshold of the patients who had received platinum analogue-based chemotherapy compared to non-platinum analogue-based chemotherapy. Conclusion Hearing loss is uncommon in patients treated with the typical gynaecological chemotherapy protocols. Hence, routine audiometric testing in these patients is not necessary. PMID:24415980

  14. Chemotherapy Combinations With Monoclonal Antibodies in Non-Hodgkin’s Lymphoma

    PubMed Central

    Kahl, Brad

    2010-01-01

    Although the use of monoclonal antibodies as single agents has had a tremendous impact on the care of patients with non-Hodgkin’s lymphoma (NHL), the greatest benefit has been generated by the addition of monoclonal antibodies to conventional cytotoxic chemotherapy. Rituximab is the monoclonal antibody responsible for all clinical improvement noted to date. The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP regimen) improves the response rate, progression-free survival (PFS), and overall survival (OS) in diffuse large B-cell lymphoma (DLBCL). Adding rituximab to CHOP chemotherapy improves response rates and PFS in mantle cell lymphoma (MCL). Finally, the addition of rituximab to a variety of chemotherapy regimens improves the response rates, PFS, and OS in follicular lymphoma (FL). Several other (epratuzumab, bevacizumab, alemtuzumab) monoclonal antibody–chemotherapy combinations are currently under study in NHL. This review will summarize the data supporting the addition of rituximab to chemotherapy in NHL and discuss preliminary data regarding the use of other monoclonal antibodies in combination with chemotherapy. PMID:18381103

  15. Adverse events in bevacizumab and chemotherapy: patient management.

    PubMed

    Blowers, Elaine; Hall, Kate

    Bevacizumab (Avastin) is an anti-angiogenic agent recently approved for the treatment of metastatic breast cancer in combination with paclitaxel. It is important that nurses are familiar with the side-effects associated with this agent--several of which differ from those seen with traditional chemotherapy agents--and how these can be optimally identified, monitored and managed. Side-effects associated with bevacizumab include hypertension, proteinuria, thromboembolic events, bleeding, cardiac toxicity, wound-healing complications and gastrointestinal perforations. Many of these are easily manageable, often without the need to discontinue bevacizumab therapy. This article, the second in a series, provides nurses with management recommendations for these toxicities in order to deliver optimal patient care and improve patients quality of life.

  16. Palonosetron for the treatment of chemotherapy-induced nausea and vomiting.

    PubMed

    Navari, Rudolph M

    2014-12-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The introduction of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists has been a major factor in the improvement of the prevention of chemotherapy-induced acute and delayed emesis. Palonosetron , a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in this drug class. Palonosetron's chemistry, pharmacodynamics, pharmacokinetics, metabolism, clinical efficacy, including comparison with other antiemetics, role in controlling nausea, potential role in multi-day chemotherapy and bone marrow transplantation, and overall safety are discussed. The clinical data in the literature have established palonosetron as the 5-HT3 receptor antagonist of choice in terms of efficacy and safety for the prevention of CINV for patients receiving moderately or highly emetogenic chemotherapy. Three international guidelines have listed palonosetron as the preferred 5-HT3 receptor antagonist. Due to its higher efficacy, the use of palonosetron may be more cost effective compared to the generic first-generation 5-HT3 receptor antagonists. Clinical organizations' pharmacy and formulary committees should consider efficacy when making recommendations for agents for the prevention of CINV.

  17. Thalidomide for Control Delayed Vomiting in Cancer Patients Receiving Chemotherapy.

    PubMed

    Han, Zhengxiang; Sun, Xuan; Jiang, Guan; Du, Xiuping

    2016-11-01

    To explore the efficacy and safety of thalidomide for the treatment of delayed vomiting, induced by chemotherapy in cancer patients. Randomized, double-blind controlled study. The Oncology Department of Affiliated Hospital of Xuzhou Medical University, Jiangsu Xuzhou, China, from January 2012 to January 2014. A total of 78 cancer patients, who had delayed vomiting observed from 24 hours to 1 week after chemotherapy, were included in the study. Patients were divided in a treatment group (40 patients, 51.28%) and a control group (38 patients, 48.71%). The treatment group received thalidomide at an oral dose of 100 mg per night; 50 mg was added daily up to a dose of 200 mg per night, if the curative effect was suboptimal and the medicine was tolerated. Both the treatment and the control groups received a drip of 10 mg azasetron 30 minutes before chemotherapy. The control group only proportions of antiemetic effects and adverse reactions were compared using the c2 test. Antiemetic effects and adverse reactions were assessed from Odds Ratios (OR) with 95% Confidence Intervals(95% CI). The effective control rate of delayed vomiting in the treatment group was significantly higher than that in the control group (c2=5.174, p=0.023). No significant difference was found between the two groups in other adverse effects of chemotherapy. Karnofsky scores or the overall self-evaluation of the patients (p>0.05). Thalidomide can effectively control the delayed vomiting of cancer patients receiving chemotherapy and the adverse reactions of the agent can be tolerated.

  18. Prebiotics: A Potential Treatment Strategy for the Chemotherapy-damaged Gut?

    PubMed

    Wang, Hanru; Geier, Mark S; Howarth, Gordon S

    2016-01-01

    Mucositis, characterized by ulcerative lesions along the alimentary tract, is a common consequence of many chemotherapy regimens. Chemotherapy negatively disrupts the intestinal microbiota, resulting in increased numbers of potentially pathogenic bacteria, such as Clostridia and Enterobacteriaceae, and decreased numbers of "beneficial" bacteria, such as Lactobacilli and Bifidobacteria. Agents capable of restoring homeostasis in the bowel microbiota could, therefore, be applicable to mucositis. Prebiotics are indigestible compounds, commonly oligosaccharides, that seek to reverse chemotherapy-induced intestinal dysbiosis through selective colonization of the intestinal microbiota by probiotic bacteria. In addition, evidence is emerging that certain prebiotics contribute to nutrient digestibility and absorption, modulate intestinal barrier function through effects on mucin expression, and also modify mucosal immune responses, possibly via inflammasome-mediated processes. This review examines the known mechanisms of prebiotic action, and explores their potential for reducing the severity of chemotherapy-induced mucositis in the intestine.

  19. Chemotherapy-associated liver injury: impact on surgical management of colorectal cancer liver metastases.

    PubMed

    Kneuertz, Peter J; Maithel, Shishir K; Staley, Charles A; Kooby, David A

    2011-01-01

    Chemotherapy is integral to the management of patients with advanced colorectal cancer liver metastases. Due to their improved efficacy, modern regimens can sometimes convert unresectable disease to a resectable state. As chemotherapy is often administered prior to hepatic resection, adverse effects on the liver are increasingly being recognized. Investigators have identified a wide spectrum of effects on the underlying liver parenchyma, ranging from mild forms of steatosis to severe steatohepatitis and sinusoidal obstruction syndrome. As the histopathologic definitions of these changes evolve, studies have identified specific patterns of hepatic injury related to the various chemotherapeutic agents. The impact of these changes on perioperative outcome after partial hepatectomy remains controversial. Timing and duration of chemotherapy may play a key role and account for discrepancies in outcomes seen among studies. In this review, we provide an overview of the spectrum of chemotherapy-associated liver injury and discuss its relevance to perioperative management of patients undergoing hepatic resection of colorectal cancer liver metastases.

  20. Paclitaxel and platinum-based chemotherapy results in transient dyslipidemia in cancer patients

    PubMed Central

    Wang, Guoping; Su, Chao; Yin, Tao

    2017-01-01

    Paclitaxel and cisplatin (TP) are common chemotherapeutic agents extensively used for treating lung and esophageal cancers. The present study reported three patients with transient hypertriglyceridemia (HTG) following TP chemotherapy. Serum triglyceride (TG) levels returned to baseline at chemotherapy intermission. No patient had any history of HTG or any evidence of pancreatitis or other complications of HTG. No regular elevation of any other serum lipids, including cholesterol, high-density lipoprotein and low-density lipoprotein, was observed. However, treatment of mice with TP decreased TG and slightly increased cholesterol. The findings of the present study suggested that TP chemotherapy results in transient dyslipidemia, and physicians must monitor TG levels during chemotherapy to avoid TG-associated complications. PMID:28357107

  1. Research in the field of antiviral chemotherapy performed in the "Stefan S. Nicolau" Institute of Virology.

    PubMed

    Eşanu, V

    1984-01-01

    A brief review is made of the research in the field of antiviral chemotherapy performed in the "Stefan S. Nicolau" Institute of Virology during the 35 years since its foundation. The investigations have mainly focused on influenza and herpes virus, but the chemotherapy of other viral infections (mumps, vaccinia, Coxsackie, etc.) has also been approached. Most of the chemotherapy agents assayed have been represented by natural preparations: immunoglobulins, interferon, hormones, vitamins, plant extracts (garlic, horse radish), bee products (propolis, royal jelly); attempts have also been made with numerous synthetic compounds. Stress is laid on the preparations already tested with a view to application in human clinic, and the prospects of chemotherapy research in the Institute of Virology are discussed.

  2. Integrative review of factors related to the nursing diagnosis nausea during antineoplastic chemotherapy 1

    PubMed Central

    Moysés, Aline Maria Bonini; Durant, Lais Corsino; de Almeida, Ana Maria; Gozzo, Thais de Oliveira

    2016-01-01

    ABSTRACT Objective: to identify factors related to the nursing diagnosis nausea among cancer patients undergoing chemotherapy. Method: integrative review conducted in four electronic databases (PUBMED, EMBASE, CINAHL and LILACS) using the key words: neoplasia, antineoplastic agents and nausea. Results: only 30 out of 1,258 papers identified met the inclusion criteria. The most frequent related factors were: being younger than 50 years old, motion sickness, being a woman, emetogenic potential of the chemotherapy, anxiety, conditioned stimulus, and expecting nausea after treatment. Conclusion: this review's findings, coupled with the incidence of nausea among cancer patients undergoing chemotherapy, reveal an important difference between evidence found and that used by NANDA International, Inc. Even though it provides an appropriate definition of related factors, it does not mention chemotherapy, despite the various studies addressing the topic using different designs and presenting various objectives and outcomes. PMID:27737380

  3. Low-dose metronomic chemotherapy: from past experience to new paradigms in the treatment of cancer.

    PubMed

    Loven, David; Hasnis, Erez; Bertolini, Francesco; Shaked, Yuval

    2013-02-01

    Low-dose metronomic (LDM) chemotherapy represents an emerging concept in the treatment of cancer. Directed against tumor cells and other types of cells, such as endothelial and immune cells, this treatment regimen alters the tumor microenvironment and suppresses innate features which support tumor growth. Ongoing Phase III clinical studies explore various applications of LDM chemotherapy, mostly combined with other anticancer agents, to act as complementary treatments to conventional maximum tolerated dose (MTD) chemotherapy. In this article we summarize preclinical and clinical experience with LDM chemotherapy, emphasizing the potential contribution of this new treatment modality to future paradigms in the systemic treatment of patients with cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Hematopoietic stem cell compartment: Acute and late effects of radiation therapy an chemotherapy

    SciTech Connect

    Mauch, P.; Constine, L.; Greenberger, J.

    1995-03-30

    The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantion. Over the past 5-10 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continue to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this toxicity such as with the increasing use of cytokines. This review describes what is known of how chemotherapy and irradiation damage stem cells and the microenvironment, how cytokines protect hematopoietic cells from radiation damage and speed marrow recovery after chemotherapy or marrow transplantation, and how various types of blood marrow cells contribute to engraftment and long-term hematopoiesis after high doses of cytotoxic agents and/or total body irradiation. 167 refs., 7 figs., 6 tabs.

  5. Therapeutic potential of cannabinoids in counteracting chemotherapy-induced adverse effects: an exploratory review.

    PubMed

    Ostadhadi, Sattar; Rahmatollahi, Mahdieh; Dehpour, Ahmad-Reza; Rahimian, Reza

    2015-03-01

    Cannabinoids (the active constituents of Cannabis sativa) and their derivatives have got intense attention during recent years because of their extensive pharmacological properties. Cannabinoids first developed as successful agents for alleviating chemotherapy associated nausea and vomiting. Recent investigations revealed that cannabinoids have a wide range of therapeutic effects such as appetite stimulation, inhibition of nausea and emesis, suppression of chemotherapy or radiotherapy-associated bone loss, chemotherapy-induced nephrotoxicity and cardiotoxicity, pain relief, mood amelioration, and last but not the least relief from insomnia. In this exploratory review, we scrutinize the potential of cannabinoids to counteract chemotherapy-induced side effects. Moreover, some novel and yet important pharmacological aspects of cannabinoids such as antitumoral effects will be discussed. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Epoetin beta for the treatment of chemotherapy-induced anemia: an update

    PubMed Central

    Galli, Luca; Ricci, Clara; Egan, Colin Gerard

    2015-01-01

    Epoetin beta belongs to the class of erythropoiesis-stimulating agents (ESAs) that are currently available to treat anemic patients receiving chemotherapy. Chemotherapy-induced anemia affects a high percentage of cancer patients and, due to its negative effects on disease outcome and the patient’s quality of life, should be treated when first diagnosed. Initial trials with ESAs have shown efficacy in improving quality of life and reducing the need for blood transfusions in patients with chemotherapy-induced anemia. However, recent meta-analyses have provided conflicting data on the impact of ESAs on survival and tumor progression. Here we provide an overview of these recent data and review the role of epoetin beta in the treatment of chemotherapy-induced anemia over the past 20 years. PMID:25784818

  7. Oral cancer: Current role of radiotherapy and chemotherapy.

    PubMed

    Huang, Shao-Hui; O'Sullivan, Brian

    2013-03-01

    The term oral cavity cancer (OSCC) constitutes cancers of the mucosal surfaces of the lips, floor of mouth, oral tongue, buccal mucosa, lower and upper gingiva, hard palate and retromolar trigone. Treatment approaches for OSCC include single management with surgery, radiotherapy [external beam radiotherapy (EBRT) and/or brachytherapy], as well as adjuvant systemic therapy (chemotherapy and/or target agents); various combinations of these modalities may also be used depending on the disease presentation and pathological findings. The selection of sole or combined modality is based on various considerations that include disease control probability, the anticipated functional and cosmetic outcomes, tumor resectability, patient general condition, and availability of resources and expertise. For resectable OSCC, the mainstay of treatment is surgery, though same practitioners may advocate for the use of radiotherapy alone in selected "early" disease presentations or combined with chemotherapy in more locally advanced stage disease. In general, the latter is more commonly reserved for cases where surgery may be problematic. Thus, primary radiotherapy ± chemotherapy is usually reserved for patients unable to tolerate or who are otherwise unsuited for surgery. On the other hand, brachytherapy may be considered as a sole modality for early small primary tumor. It also has a role as an adjuvant to surgery in the setting of inadequate pathologically assessed resection margins, as does postoperative external beam radiotherapy ± chemotherapy, which is usually reserved for those with unfavorable pathological features. Brachytherapy can also be especially useful in the re-irradiation setting for persistent or recurrent disease or for a second primary arising within a previous radiation field. Biological agents targeting the epithelial growth factor receptor (EGFR) have emerged as a potential modality in combination with radiotherapy or chemoradiotherapy and are currently under

  8. Osteogenic Sarcoma: Systemic Chemotherapy Options for Localized Disease.

    PubMed

    Harrison, Douglas J; Schwartz, Cindy L

    2017-04-01

    Treatment for osteosarcoma, the most common malignant tumor of bone in children and adolescents, has not changed in decades. Treatment is multimodal, employing neoadjuvant chemotherapy followed by aggressive and complete surgical resection to achieve negative margins and a prolonged course of adjuvant chemotherapy. The primary tumor is usually successfully managed via surgery, but micrometastases are likely present in most patients at diagnosis. Death is the result of tumor recurrence in the lungs or more rarely in other bones despite aggressive treatment regimens and is likely attributable to innate resistance to chemotherapy. Better therapies are desperately needed. The three most active agents-high-dose methotrexate, doxorubicin, and cisplatin-commonly referred to as "MAP," form the backbone of therapy. After 2 cycles of MAP, surgical resection is performed of all sites of disease if possible. Histologic response following neoadjuvant chemotherapy is prognostic in non-metastatic osteosarcoma, but augmentation of adjuvant therapy for poor responders with additional agents (ifosfamide, etoposide) has not improved outcome. Inclusion of immunotherapy into treatment regimens is promising. Specifically, liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE), a macrophage and monocyte activator, improved 10-year overall survival for patients with localized disease, with a similar pattern of response in patients with metastatic disease. L-MTP-PE (mifamurtide) is approved and in widespread use in Europe and elsewhere but has not been approved for use by the Federal Drug Administration in the USA. Identifying novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research.

  9. Treatment of Nausea and Vomiting During Chemotherapy

    PubMed Central

    Mustian, Karen M; Devine, Katie; Ryan, Julie L; Janelsins, Michelle C; Sprod, Lisa K; Peppone, Luke J; Candelario, Grace D; Mohile, Supriya G; Morrow, Gary R

    2014-01-01

    Nausea and vomiting are two of the most troubling side effects patients experience during chemotherapy. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still a major problem for patients receiving chemotherapy. Many cancer patients will delay or refuse future chemotherapy treatments and contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting and the recommended guidelines for treatment. PMID:24466408

  10. Influenza vaccination in children being treated with chemotherapy for cancer.

    PubMed

    Goossen, Ginette M; Kremer, Leontien C M; van de Wetering, Marianne D

    2013-08-01

    Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear. 1. To assess the efficacy of influenza vaccination in stimulating an immunological response in children with cancer during chemotherapy, compared with control groups.2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or in stimulating immunological response in children with cancer treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.3. To identify the adverse effects associated with influenza vaccines in children with cancer treated with chemotherapy, compared with other control groups. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2012) and EMBASE (1980 to 2012) up to August 2012. We also searched reference lists of relevant articles and conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Infectious Diseases Society of America (IDSA), the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Paediatric Oncology (SIOP). We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serological response to influenza vaccination of children with cancer was compared with that of control groups. We also considered RCTs and CCTs that compared the effects of influenza vaccination on clinical response and/or immunological response in children with cancer being treated with chemotherapy, compared with placebo, no intervention or different dosage schedules. Two independent review authors assessed the methodological quality of included studies and extracted the data. We included 1 RCT and 9 CCTs

  11. [Chemotherapy-free treatment of chronic lymphocytic leukemia?].

    PubMed

    Wendtner, C-M

    2013-10-01

    Treatment of CLL patients with conventional cytotoxic agents is often combined with significant toxicity that prevents broad application especially in elderly patients. In addition, relapse frequently occurs after application of conventional chemotherapy in CLL. Recently several new chemo-free treatment options have been introduced within clinical trials. Among them are monoclonal antibodies, most of them targeting the CD20 molecule: besides the licensed drugs rituximab and ofatumumab obinutuzumab, although in combination with chemotherapy, has recently shown high clinical efficacy in front-line treatment of elderly patients with CLL. Lenalidomide as monotherapy has demonstrated clinical efficacy in patients with relapsed disease and first data within clinical trials have been generated in the front-line setting. A promising class of novel agents has been designed to block aberrant signaling from the B-cell receptor. Ibrutinib acts by inhibiting the Bruton's tyrosine kinase (BTK) while idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform. Another class of drugs with potential impact for chemo-free treatment strategies in CLL are the BH3-mimetic inhibitors of the Bcl-2 family of pro-survival proteins. Other interesting candidate drugs that are currently explored for CLL patients include small modular immunopharmaceutical (SMIP) proteins (e. g. TRU-016), CDK inhibitors (e. g. dinaciclib), HDAC inhibitors and others. Given all these novel agents and targets, chemo-free or at least chemo-reduced concepts may become reality in the near future for our patients suffering from CLL.

  12. Cardiotoxicity of Molecularly Targeted Agents

    PubMed Central

    Hedhli, Nadia; Russell, Kerry S

    2011-01-01

    Cardiac toxicity of molecularly targeted cancer agents is increasingly recognized as a significant side effect of chemotherapy. These new potent therapies may not only affect the survival of cancer cells, but have the potential to adversely impact normal cardiac and vascular function. Unraveling the mechanisms by which these therapies affect the heart and vasculature is crucial for improving drug design and finding alternative therapies to protect patients predisposed to cardiovascular disease. In this review, we summarize the classification and side effects of currently approved molecularly targeted chemotherapeutics. PMID:22758623

  13. 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.

  14. Biological Agents

    MedlinePlus

    ... is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. Murphy/CDC OSHA's Ebola webpage provides ... OSHA offers, visit OSHA's Workers' page. In Focus: Ebola Frederick A. Murphy/CDC OSHA's Ebola webpage provides ...

  15. Changes in Ovarian Stromal Function and Associated Symptoms in Premenopausal Women Undergoing Chemotherapy for Breast Cancer

    DTIC Science & Technology

    2008-08-01

    Greeene Climacteric Scale, Profile of Mood States, Schwartz Fatigue Scale and a menses diary. Data analysis involved descriptive statistics, plots...premature menopause as a result of chemotherapy agents used to treat breast cancer. Menopause -related symptoms are salient management issues for...symptoms. A longitudinal, descriptive design was used. Data, including both subjective and objective measures of menopause - related phenomena, were

  16. Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced Axonal Neuropathy

    DTIC Science & Technology

    2013-05-01

    COVERED 1 May 201 - 30 Apr 201 4. TITLE AND SUBTITLE : Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced axonal...Introduction-page 1 Results- page 1,2,3 Conclusion-page 3 Introduction: Taxol is an antineoplastic agent, which is used for the treatment of

  17. Chemotherapy-induced endometrial pathology: mimicry of malignancy and viral endometritis

    PubMed Central

    Kim, Eun Kyung; Yoon, Gun; Kim, Hyun-Soo

    2016-01-01

    Chemotherapy is a common type of preoperative neoadjuvant treatment and postoperative adjuvant or palliative therapy for many different types of malignancies. Certain chemotherapeutic agents can induce bizarre epithelial atypia that mimics malignancy. Unfamiliarity with these changes could potentially cause confusion with a neoplastic or infectious process. The endometrium is one of the few sites where chemotherapy-induced epithelial atypia has not been appreciated. We identified four patients with marked cytologic atypia of the endometrial glandular epithelium from the surgical pathology files of Severance Hospital. The histopathologic features, immunostaining results and medical records of these patients were reviewed. All patients underwent hysteroscopic examination with endometrial curettage for investigation of vaginal bleeding. They had previously undergone chemotherapy for uterine cervical cancer (n=1), rectal cancer (n=2) and myelodysplastic syndrome (n=1). The chemotherapy regimens included alkylating agents (busulfan, cyclophosphamide, ifosfamide, cisplatin, and oxaliplatin), pyrimidine antagonists (capecitabine, decitabine, and 5-fluorouracil), taxanes (paclitaxel), and topoisomerase inhibitors (irinotecan and etoposide). On histopathological examination, the atypical epithelial changes included marked nuclear enlargement and pleomorphism, a degenerative-looking chromatin pattern, abundant microvacuolated cytoplasm, and preservation of the nuclear/cytoplasmic ratio. This study demonstrates that certain chemotherapeutic agents may cause bizarre, reactive atypia of the endometrial glandular epithelium. These changes should not be interpreted as neoplastic or infectious in nature. An awareness of prior exposure to cytotoxic agents and a familiarity with the nature and distribution of these bizarre alterations is essential to avoid misinterpretation of the morphologic features and prevent unnecessary treatment. PMID:27347355

  18. Application of biodynamic imaging for personalized chemotherapy in canine lymphoma

    NASA Astrophysics Data System (ADS)

    Custead, Michelle R.

    Biodynamic imaging (BDI) is a novel phenotypic cancer profiling technology which characterizes changes in cellular and subcellular motion in living tumor tissue samples following in vitro or ex vivo treatment with chemotherapeutics. The ability of BDI to predict clinical response to single-agent doxorubicin chemotherapy was tested in ten dogs with naturally-occurring non-Hodgkin's lymphomas (NHL). Pre-treatment tumor biopsy samples were obtained from all dogs and treated with doxorubicin (10 muM) ex vivo. BDI captured cellular and subcellular motility measures on all biopsy samples at baseline and at regular intervals for 9 hours following drug application. All dogs subsequently received treatment with a standard single-agent doxorubicin protocol. Objective response (OR) to doxorubicin and progression-free survival time (PFST) following chemotherapy were recorded for all dogs. The dynamic biomarkers measured by BDI were entered into a multivariate logistic model to determine the extent to which BDI predicted OR and PFST following doxorubicin therapy. The model showed that the sensitivity, specificity, and accuracy of BDI for predicting treatment outcome were 95%, 91%, and 93%, respectively. To account for possible over-fitting of data to the predictive model, cross-validation with a one-left-out analysis was performed, and the adjusted sensitivity, specificity, and accuracy following this analysis were 93%, 87%, and 91%, respectively. These findings suggest that BDI can predict, with high accuracy, treatment outcome following single-agent doxorubicin chemotherapy in a relevant spontaneous canine cancer model, and is a promising novel technology for advancing personalized cancer medicine.

  19. Reversibility of chemotherapy-related liver injury.

    PubMed

    Vigano, Luca; De Rosa, Giovanni; Toso, Christian; Andres, Axel; Ferrero, Alessandro; Roth, Arnaud; Sperti, Elisa; Majno, Pietro; Rubbia-Brandt, Laura

    2017-07-01

    Chemotherapy-associated liver injury (CALI) increases the risk of liver resection and may prejudice further surgery and chemotherapy. The reversibility of CALI is therefore important; however, no data concerning this are available. This study aimed to retrospectively analyze the reversibility of CALI in patients undergoing liver resection for colorectal metastases. All resections of colorectal liver metastases after oxaliplatin and/or irinotecan-based chemotherapy were included. First, liver resections were stratified by time between end of chemotherapy and hepatectomy and several possible cut-off values tested. CALI prevalence in various groups was compared. Second, CALI in the two specimens from each patient who had undergone repeat liver resections without interval chemotherapy were compared. Overall, 524 liver resections in 429 patients were analyzed. The median interval chemotherapy-surgery was 56days (15-1264). CALI prevalence did not differ significantly between groups with a chemotherapy-surgery interval <270days. Grade 2-3 sinusoidal dilatation (SOS, 19.4% vs. 40.0%, p=0.022) and nodular regenerative hyperplasia (NRH, 6.5% vs. 20.1%, p=0.063) occurred less frequently in patients with an interval >270days (n=31); prevalence of steatosis and steatohepatitis was similar in all groups. A chemotherapy-surgery interval >270days was an independent protector against Grade 2-3 SOS (p=0.009). Forty-seven patients had repeat liver resection without interval chemotherapy. CALI differed between surgeries only for a chemotherapy-surgery interval >270days (n=15), Grade 2-3 SOS having regressed in 4/5 patients and NRH in 7/8; whereas steatosis and steatohepatitis had persisted. CALI persists for a long time after chemotherapy. SOS and NRH regress only after nine months without chemotherapy, whereas steatosis and steatohepatitis persist. The patients affected by colorectal liver metastases often receive chemotherapy before liver resection, but chemotherapy causes liver

  20. Potentiating effects of caffeine on teratogenicity of alkylating agents in mice

    SciTech Connect

    Fujii, T.; Nakatsuka, T.

    1983-08-01

    Teratogenic to subteratogenic doses of x-ray, mitomycin C, MNNG, thio-TEPA, cyclophosphamide, and chlorambucil were administered to pregnant ICR mice together with caffeine at doses of 12.5, 25, or 50 mg/kg on day 11 of gestation. Fetuses were examined for gross malformations on day 18 of gestation. The teratogenicity of mitomycin C was significantly potentiated by caffeine at a dose as low as 12.5 mg/kg. The teratogenicity of chlorambucil was also significantly potentiated by caffeine at 50 mg/kg, but similar potentiation was not observed for x-ray, MNNG, thio-TEPA, and cyclophosphamide.

  1. Oral manifestations of systemic chemotherapy and their management.

    PubMed

    Carl, W

    1986-01-01

    Many antineoplastic drugs in use now have cytotoxic side effects that also manifest in the oral cavity or influence dental management. Chemotherapeutic agents that have a high potential for precipitating oral mucosal damage and bone marrow depression are methotrexate, cyclophosphamide, daunorubicin, doxorubicin hydrochloride, 5-fluorouracil, bleomycin, nitrogen mustard, cytosine-arabinoside, 6-mercaptopurine, busulfan, and L-phenylalanine mustard. Mucositis may lead to neglected oral hygiene, which in turn may cause a chain reaction of local infections, bleeding, and septicemia in myelosuppressed patients. Preventive oral care before chemotherapy and active oral care during therapy are necessary for compromised patients. A protocol for oral care is described.

  2. [Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC): evaluation, prevention and policies to avoid occupational exposure for operating room personnel].

    PubMed

    Simon, L; Halilou, M-C; Gladieff, L; Gadiou, M; Herin, F; Hennebelle, I; Chatelut, E; Ferron, G

    2009-10-01

    To develop a treatment strategy for peritoneal carcinomatosis using a combination of extended peritoneal resections, local destructive procedures and hyperthermic intraperitoneal chemotherapy creates great concern between healthcare workers involved in these procedures. New professional risks exist: risk of exposure to cytotoxic drugs, environmental risks (inhalation of smoke, aerosolization of chemotherapy agents). Information, education and training of healthcare workers is mandatory in order to ensure proper evaluation, prevention, and management of professional exposure risks in coordination with the occupational health office.

  3. [The chemoprophylaxis and chemotherapy of opportunistic infections].

    PubMed

    Mel'nikova, V M; Gracheva, N M; Belikov, G P; Blatun, L A; Shcherbakova, E G

    1993-01-01

    Actual problems of organization and performance of chemoprophylaxis and chemotherapy of surgical opportunistic infections are discussed with an account of the main principles of and new approaches to the use of antibacterial drugs. The analysis of the authors' observations showed that the pre- and postoperative use of parenteral antibacterial drugs such as cephalosporins (cefazolin and ceftriaxone) and their combinations with aminoglycosides, the simultaneous use of beta-lactams and lysozyme, the local application of new ointments based on polyethylenglycol, foaming agents and gentacycol were prophylactically efficient in patients with high risk of surgical infections. Endolymphatic administration of gentamicin and cefotaxime was highly efficient in the treatment and prophylaxis of severe surgical infections with lymphogenous dissemination of the pathogen or its risk. In the prophylaxis of endogenous infections special attention should be paid to the suppression of the opportunistic intestinal microflora by the use of fluorquinolones and selective decontamination followed by the correction of the intestinal microbiocenosis with probiotics (bifidobacteria), lysozyme and immunological lactoglobulins as dosage forms or dry milk biologically active additives to children diet and dietotherapy.

  4. Chemotherapy-induced neuropathy: A comprehensive survey.

    PubMed

    Miltenburg, N C; Boogerd, W

    2014-08-01

    Chemotherapy induced peripheral neuropathy (CIPN) is a potentially dose limiting side effect of commonly used chemotherapeutic agents like taxanes, vinca-alkaloids, platinum compounds, bortezomib and thalidomide. Supposed pathogenetic mechanisms of CIPN are axonopathy through dying back axon damage and neuronopathy in which the cell bodies of the dorsal root ganglia are involved. The exact pathophysiology however is not clear and different underlying mechanisms have been proposed for different classes of anti-cancer drugs. Sensory symptoms, like pain, numbness and tingling are most common, but motor weakness, autonomic dysfunction and even cranial nerve involvement may occur. CIPN can be painful and/or disabling, causing significant loss of functional abilities and decreasing quality of life. This can lead to dose reductions, discontinuation of treatment and may thus, ultimately, affect survival. Risk factors for CIPN include dose per cycle, cumulative dose, treatment schedule, duration of infusion, administration of other chemotherapeutics, comorbidity and pre-existing peripheral neuropathy. The exploration of polymorphisms in genes associated with incidence or severity of neuropathy might result in identifying individuals being at higher risk of neurotoxicity. An update on genes possibly associated with CIPN is given. CIPN may be reversible or be more or less permanent. Many preventive and treatment strategies have been explored, without significant efficacy up till now. In this review we describe the different drug-related characteristics of CIPN, pharmacogenomic studies, neurophysiological findings, treatment and outcome, and neuroprotective strategies.

  5. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

    du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  6. The Effect of Neoadjuvant Chemotherapy Compared to Adjuvant Chemotherapy in Healing after Nipple-Sparing Mastectomy.

    PubMed

    Frey, Jordan D; Choi, Mihye; Karp, Nolan S

    2017-01-01

    Nipple-sparing mastectomy is the latest advancement in the treatment of breast cancer. The authors aimed to investigate the effects of neoadjuvant and adjuvant chemotherapy in nipple-sparing mastectomy. Patients undergoing nipple-sparing mastectomy from 2006 to June of 2015 were identified. Results were stratified by presence of neoadjuvant or adjuvant chemotherapy. A total of 840 nipple-sparing mastectomies were performed. Twenty-eight were in those who received neoadjuvant chemotherapy and 93 were in patients receiving adjuvant chemotherapy. Patients receiving both neoadjuvant and adjuvant chemotherapy were included in the neoadjuvant group. Nipple-sparing mastectomies that received neoadjuvant (with or without adjuvant) chemotherapy were compared to those in patients who received adjuvant chemotherapy. Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have explantation (p = 0.0239) and complete nipple-areola complex necrosis (p = 0.0021). Those with neoadjuvant (with or without adjuvant) chemotherapy were more likely to have implant explantation (p = 0.0015) and complete nipple-areola complex necrosis (p = 0.0004) compared to those with no chemotherapy. Compared to nipple-sparing mastectomies in patients with no chemotherapy, those with adjuvant chemotherapy were more likely to have a hematoma (p = 0.0021). Those that received both neoadjuvant and adjuvant chemotherapy were more likely to have complete nipple-areola complex necrosis compared with both the neoadjuvant chemotherapy-only and adjuvant chemotherapy-only groups (p < 0.0001). Nipple-sparing mastectomy is safe to perform in the setting of neoadjuvant and adjuvant chemotherapy. As a whole, neoadjuvant (with or without adjuvant) chemotherapy increases risk of complications. Therapeutic, III.

  7. 5-HT3 receptors as important mediators of nausea and vomiting due to chemotherapy.

    PubMed

    Navari, Rudolph M

    2015-10-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. The first generation 5-HT3 receptor antagonists have been very effective in the control of chemotherapy induced emesis in the first 24 h postchemotherapy (acute emesis), but have not been as effective against delayed emesis (24-120 h postchemotherapy). Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a FDA approved antipsychotic that blocks multiple neurotransmitters: dopamine at D1, D2, D3, D4 brain receptors, serotonin at 5-HT2a, 5-HT2c, 5-HT3, 5-HT6 receptors, catecholamines at alpha1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H1 receptors, has emerged in recent trials as an effective preventative agent for chemotherapy-induced emesis and nausea, as well as a very effective agent for the treatment of breakthrough emesis and nausea. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.

  8. The use of consequential reasoning in cancer chemotherapy.

    PubMed

    Hudson, D L; Cohen, M E; Hudson, S E

    2001-01-01

    Knowledge-based decision support systems traditionally rely on condition-action rule structures, an adequate representation for simple decisions. In complex domains an important part of decision-making includes analysis of the consequences of a decision. Consequential reasoning is particularly important in medicine as potential risk and/or benefit can be included. In this paper, a knowledge structure and inference engine is described that permits the representation and analysis of consequential reasoning in a computer-assisted decision support system. The use of consequential reasoning is then illustrated in an application designed to assist in cancer chemotherapy decisions. The result is a method that is sensitive to individual patient reactions to chemotherapy agents, permitting an individualized approach to therapy. Individualized drug therapy is becoming increasingly feasible due to advances made in the field of genomics. The system is structured so that new information can be incorporated easily. Although the application shown here is to chemotherapy, the general methodology can be used in any area in which the consequences should significantly influence the decision.

  9. The effect of chemotherapy on the growing skeleton.

    PubMed

    van Leeuwen, B L; Kamps, W A; Jansen, H W; Hoekstra, H J

    2000-10-01

    With the increasing use of high dose (poly)chemotherapy schedules in the treatment of childhood cancer it is particularly important to know the adverse effects of these treatments. Growth is a complex mechanism affected not only by chemotherapy but also by the malignancy itself as well as nutritional status, the use of corticosteroids and (cranial) radiation. In vitro and animal studies are often the most useful in determining the effect of a single chemotherapeutic agent on the growing skeleton. In vitro studies have shown doxorubicin, actinomycin D and cisplatin to have a direct effect on growth plate chondrocytes that in animals results in decreased growth and final height. Clinical studies with multiagent chemotherapy have demonstrated that antimetabolites decrease bone growth and final height. Childhood cancer survivors are at risk of a reduced bone mineral density, mainly due to methotrexate, ifosfamide and corticosteroids. This reduced bone mineral density persists into adult life and may increase bone fracture risk at an older age. Copyright 2000 Harcourt Publishers Ltd.

  10. Intraepidermal nerve fibre density in cancer patients receiving adjuvant chemotherapy.

    PubMed

    Koskinen, Mika J; Kautio, Anna-Liisa; Haanpää, Maija L; Haapasalo, Hannu K; Kellokumpu-Lehtinen, Pirkko-L; Saarto, Tiina; Hietaharju, Aki J

    2011-12-01

    Chemotherapy-induced neuropathy is a common adverse event in patients receiving vinca alcaloids, platinum derivatives and taxanes. However, the underlying pathogenetic mechanisms have not been completely elucidated. We set up a prospective pilot study on skin biopsies in newly diagnosed cancer patients receiving neurotoxic chemotherapeutic agents as adjuvant treatment in order to study the occurrence of small-fibre pathology and its relationship to clinical symptoms. Skin biopsies from distal leg were performed in 12 patients before, during and after chemotherapy. Using light microscopy, the intraepidermal nerve fibre (IENF) density was determined from the skin biopsies by counting morphometrically the immunopositive nerves per epidermal area. Reduced IENF density was observed in eight patients at baseline. During the follow-up, the IENF density increased significantly in six patients and remained unchanged in two. In four patients, the IENF density was normal both at baseline and at the end of the follow-up period. Neuropathic symptoms were manifested in nine patients, but no association with the IENF count was found. During chemotherapy, results from patients revealed different evolutionary patterns of IENF density, but symptoms and IENF density were not related.

  11. Emerging treatments in chemotherapy-induced nausea and vomiting.

    PubMed

    Grunberg, Steven M; Slusher, Barbara; Rugo, Hope S

    2013-02-01

    Chemotherapy-induced nausea and vomiting (CINV) is a concern for many cancer patients. It can have an enormous impact on quality of life. CINV occurring in the first 24 hours after treatment is considered acute, and CINV occurring on days 2 through 5 after treatment is considered delayed. Anticipatory nausea and depression can also occur when patients are reminded of their chemotherapy treatment. CINV can lead to weight changes, fatigue, and the need for additional medications. Even mild to moderate CINV can increase health care utilization and costs, as well as delay treatment. Nausea and vomiting are separate events, although their mechanisms are entwined. Drugs that stop vomiting do not necessarily treat nausea. Control of CINV allows patients to complete treatment and to minimize use of health care resources and additional medications. Current antiemesis agents, such as 5-hydroxytryptamine-3 (5-HT3) antagonists and neurokinin-1 (NK-1) antagonists, have markedly decreased hospitalization for chemotherapy and have nearly eliminated acute emesis. The second-generation 5-HT3 receptor palonosetron has a unique pharmacology that makes it especially effective at preventing delayed emesis.

  12. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  13. [REACTIVATION OF TUBERCULOSIS PRESENTING WITH EMPYEMA DUE TO ANTICANCER CHEMOTHERAPY FOR DIFFUSE LARGE B CELL LYMPHOMA].

    PubMed

    Yuba, Tatsuya; Hatsuse, Mayumi; Kodama, Mai; Uda, Sayaka; Yoshimura, Akihiro; Kurisu, Naoko

    2016-04-01

    A 79-year-old man with a history of tuberculosis was found to have chronic empyema in the right lung and was diagnosed with malignant diffuse large-cell lymphoma (Ann Arbor stage IIE). After completion of one course of rituximab plus cyclophosphamide, pirarubicin, vincristine, and prednisolone (R-CHOP) chemotherapy, the patient developed lung abscess and sepsis caused by Streptococcus intermedius. This condition was treated with antimicrobial agents, and chemotherapy was resumed. After the second course, the chemotherapy regimen was continued without prednisolone, and after administration of the third course, a chest wall mass was found in the right lung. An acid-fast bacillus smear test of the abscess aspirate was positive, and Mycobacterium tuberculosis was detected in a polymerase chain reaction assay, leading to a diagnosis of perithoracic tuberculosis. Chemotherapy for the lymphoma was discontinued, and treatment with four oral antitubercular agents was started. This treatment led to remission of perithoracic tuberculosis. In Japan, tuberculous scar and chronic empyema are relatively common findings, and relapse of tuberculosis should always be considered for patients with these findings during chemotherapy and immunosuppressive therapy.

  14. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  15. Rolapitant for the prevention of delayed nausea and vomiting over initial and repeat courses of emetogenic chemotherapy.

    PubMed

    Rapoport, Bernardo; van Eeden, Ronwyn; Smit, Teresa

    2017-01-01

    Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. Although sustained antiemetic control across repeated chemotherapy cycles is important for cancer treatment continuation, few studies have investigated the efficacy of antiemetic prophylaxis over multiple chemotherapy cycles. Areas covered: Here we discuss the use of antiemetic hydroxytryptamine type 3 (5-HT3) receptor and neurokinin (NK)-1 receptor antagonists for prevention of CINV, limiting our review to clinical trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1 receptor antagonist rolapitant. 5-HT3 receptor antagonists may be effective in controlling CINV over repeated chemotherapy cycles, but evidence comes primarily from noncomparative studies. NK-1 receptor antagonists provide increased protection against CINV but differences in endpoint selection and methods of analysis preclude meaningful comparisons between agents. Rolapitant shows sustained control of emesis and nausea over multiple cycles of chemotherapy, and compared to other NK-1 receptor antagonists, has a longer half-life and reduced potential for cytochrome P450 3A4-mediated drug-drug interactions. Expert commentary: Trial design should be a key consideration in future studies of CINV therapies, including analytical methods utilized, choice of endpoints, and methods for accounting for nonresponders and patient attrition over multiple cycles of chemotherapy.

  16. Chemotherapy

    MedlinePlus

    ... cause nerve problems and burning, numbness, tingling, or shooting pain in the fingers and toes. Certain types ... more comfortable wearing hats, scarves, or wigs to school or other events. Or, you may look great ...

  17. Chemotherapy

    MedlinePlus

    ... cells to get better. Because everyone's different, some people will have fewer side effects than others. Common side effects of chemo are ... infections easily. Medicines are available that can help people feel better if they have side effects from chemo. Doctors, nurses, and other members of ...

  18. Chemotherapy

    MedlinePlus

    ... Use only mild shampoos and hair products. And talk with your doctor about sunscreen if you're going to be outside. Practice infection protection. Wash your hands before eating, after using the bathroom, and after touching animals. If friends or family members have infections such ...

  19. [Use of chemotherapy during pregnancy].

    PubMed

    Benardete-Harari, Denise N; Kershenovich-Gersson, Janisse; Meraz-Ávila, Diego; Galnares-Olalde, Javier Andrés; Olaya-Guzmán, Emilio José

    2016-01-01

    The presence of malignant tumors during pregnancy complicates the management of both tumor and pregnancy, since any diagnostic or therapeutic intervention could imply risks that may bring on detrimental effects to fetus or mother. The risks involved in exposing a fetus to cytotoxic therapy are associated to gestational age and the time of in utero exposure to that therapy. Cancer treatment has two different objectives: local control by surgery and radiotherapy, and one that seeks to eradicate systemic disease through chemotherapy, immunotherapy, hormone therapy, or targeted therapies.

  20. Successful chemotherapy of transfusion babesiosis.

    PubMed

    Wittner, M; Rowin, K S; Tanowitz, H B; Hobbs, J F; Saltzman, S; Wenz, B; Hirsch, R; Chisholm, E; Healy, G R

    1982-05-01

    We describe babesiosis transmitted by transfusion. The infected blood donor was identified and a minimum period of infectivity of the donor's blood was established. We report a new modality for chemotherapy consisting of quinine plus clindamycin, and a new endemic focus for this zoonosis on Fire Island, New York. There are insufficient data to establish a reasonably safe period after which visitors and residents of Babesia-endemic foci can become blood donors. Screening of such persons by a rapid serologic test, such as the ELISA or immunofluorescent antibody tests, is suggested.

  1. [Adjuvant chemotherapy for patients with rectal cancer].

    PubMed

    Qvortrup, Camilla; Mortensen, John Pløen; Pfeiffer, Per

    2013-09-09

    A new Cochrane meta-analysis evaluated adjuvant chemotherapy (5-fluorouracil (5FU)-based, not modern combination chemotherapy) in almost 10,000 patients with rectal cancer and showed a 17% reduction in mortality corresponding well to the efficacy observed in recent studies, which reported a reduction in mortality just about 20%. The authors recommend adjuvant chemotherapy which is in accordance with the Danish national guidelines where 5-FU-based chemotherapy is recommended for stage III and high-risk stage II rectal cancer.

  2. Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells.

    PubMed

    Chan, Tze-Sian; Hsu, Chung-Chi; Pai, Vincent C; Liao, Wen-Ying; Huang, Shenq-Shyang; Tan, Kok-Tong; Yen, Chia-Jui; Hsu, Shu-Ching; Chen, Wei-Yu; Shan, Yan-Shen; Li, Chi-Rong; Lee, Michael T; Jiang, Kuan-Ying; Chu, Jui-Mei; Lien, Gi-Shih; Weaver, Valerie M; Tsai, Kelvin K

    2016-12-12

    Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif-positive (ELR(+)) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR(+) chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy. © 2016 Chan et al.

  3. Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer.

    PubMed

    Navari, Rudolph M

    2010-07-01

    Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient characteristics (e.g., female gender, younger age, low alcohol consumption and history of motion sickness) are the major risk factors for CINV. This article provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, which has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared with the first-generation 5-HT(3) receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy and had a similar safety profile. Owing to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation.

  4. Current Pharmacotherapy for Chemotherapy-Induced Nausea and Vomiting in Cancer Patients

    PubMed Central

    Janelsins, Michelle C.; Tejani, Mohamed; Kamen, Charles; Peoples, Anita; Mustian, Karen M.; Morrow, Gary R.

    2014-01-01

    Introduction Nausea and vomiting are two of the most frequent and troubling side effects patients experience during chemotherapy, interfering with compliance with cancer therapies and quality of life. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still major problems for patients receiving chemotherapy. Many cancer patients consider delaying future chemotherapy cycles and some contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. Areas Covered The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting, the recommended guidelines for treatment, current agents in late-stage clinical trials, and future research needs to address the continued challenges of treatment-related nausea and vomiting. Expert Opinion Despite advances in pharmaceutical and behavioral therapies, and the provision of standard clinical guidelines for effectively managing chemotherapy-induced nausea and vomiting (CINV), patients continue to experience CINV. Moreover, control of nausea, acute and delayed, and anticipatory nausea and vomiting (ANV) remains an important, unmet need among cancer patients. It is critical to focus attention on better understanding the mechanisms underlying nausea, anticipatory symptoms, and delayed symptoms. PMID:23496347

  5. PDE5 inhibitors enhance the lethality of standard of care chemotherapy in pediatric CNS tumor cells

    PubMed Central

    Roberts, Jane L; Booth, Laurence; Conley, Adam; Cruickshanks, Nichola; Malkin, Mark; Kukreja, Rakesh C; Grant, Steven; Poklepovic, Andrew; Dent, Paul

    2014-01-01

    We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease. PMID:24651037

  6. Hepatic Lesions that Mimic Metastasis on Radiological Imaging during Chemotherapy for Gastrointestinal Malignancy: Recent Updates

    PubMed Central

    You, Sung-Hye; Kim, Yeul Hong

    2017-01-01

    During chemotherapy in patients with gastrointestinal malignancy, the hepatic lesions may occur as chemotherapy-induced lesions or tumor-associated lesions, with exceptions for infectious conditions and other incidentalomas. Focal hepatic lesions arising from chemotherapy-induced hepatopathies (such as chemotherapy-induced sinusoidal injury and steatosis) and tumor-associated eosinophilic abscess should be considered a mimicker of metastasis in patients with gastrointestinal malignancy. Accumulating evidence suggests that chemotherapy for gastrointestinal malignancy in the liver has roles in both the therapeutic effects for hepatic metastasis and injury to the non-tumor bearing hepatic parenchyma. In this article, we reviewed the updated concept of chemotherapy-induced hepatopathies and tumor-associated eosinophilic abscess in the liver, focusing on the pathological and radiological findings. Awareness of the causative chemo-agent, pathophysiology, and characteristic imaging findings of these mimickers is critical for accurate diagnosis and avoidance of unnecessary exposure of the patient to invasive tissue-based diagnosis and operations. PMID:28458594

  7. Activated expression of the chemokine Mig after chemotherapy contributes to chemotherapy-induced bone marrow suppression and lethal toxicity.

    PubMed

    Lu, Huili; Zhu, Shunying; Qian, Lan; Xiang, Di; Zhang, Wu; Nie, Aifang; Gao, Jin; Wu, Mingyuan; Gao, Jinming; Lu, Bao; Yu, Yan; Han, Wei; Moldenhauer, Anja

    2012-05-24

    Alterations in gene expression after chemotherapy may potentially help to identify mediators that induce suppression or regeneration in bone marrow. This paper reports our observation that the expression of the chemokine monokine induced by IFN-γ (Mig) and its receptor CXCR3 was significantly activated in mice after treatment with the chemotherapeutic agent 5-fluorouracil (5-FU). The neutralization of antibodies against the activated Mig increased the survival rate and accelerated BM recovery after chemotherapy. In addition, elevation of Mig plasma levels after 5-FU treatment corresponded with increased mortality. The cell cycle-inhibiting effect of the prophylactic administration of Mig protected hematopoietic progenitor cells (HPCs) from 1-β-d-arabinofuranosylcytosine in spleen colony assays and enhanced the irradiated recipients' survival. In CXCR3(-/-) mice, Mig did not propagate BM suppression, indicating that the suppressive effect of Mig is dependent on CXCR3. On the one hand, Mig stimulated p70 S6K and Erk1/2 pathways in mesenchymal stroma cells, inhibiting mesenchymal stroma cell-dependent HPC expansion. Moreover, Mig suppressed the STAT5 pathway in HPCs, inhibiting leukocyte differentiation. Our results strongly suggest that Mig contributes to the acute lethal toxicity arising from 5-FU administration. Neutralization of Mig may offer new strategies to alleviate BM toxicity with potentially dramatic implications for chemotherapy.

  8. Betulin-loaded PEDOT films for regional chemotherapy.

    PubMed

    Krukiewicz, Katarzyna; Cichy, Magdalena; Ruszkowski, Piotr; Turczyn, Roman; Jarosz, Tomasz; Zak, Jerzy K; Lapkowski, Mieczyslaw; Bednarczyk-Cwynar, Barbara

    2017-04-01

    Chemotherapy is one of the most commonly used cancer treatments. Even so, it has significant adverse effects on healthy tissues. These effects can be avoided through the use of regional chemotherapy, an approach based on delivering the anti-cancer agents locally, to the site of cancer tissue accumulation. Among the different classes of biomaterials that are used as drug carriers, conducting polymers allow reversible, electrostatic immobilization and controlled release of a variety of compounds. In this work, we describe a method for producing surfaces possessing anti-cancer activity, which are a potential tool for regional chemotherapy. Our method consists of covering the surface with a conducting polymer matrix, followed by loading that matrix with cytotoxic compounds. We have chosen betulin as the model compound for this study, as it is commonly available triterpene that exhibits cytotoxicity against a variety of tumor cell lines. The presence of betulin in the polymer matrix is confirmed by SEM, EDS and IR spectroscopy. The release of betulin is carried out using two protocols, i.e. passive mode (open circuit conditions) or active (application of constant potential) mode. The biological activity of betulin that was released from the matrix is confirmed by its toxic effect against KB and MCF-7 cancer cell lines (IC50 values of 13.34±0.88μg/mL and 12.57±1.81μg/mL for KB and MCF-7, respectively). The described method of surface modification is shown to be an effective mean of producing surfaces that possess anti-cancer activity, serving as advantageous materials for regional chemotherapy applications.

  9. Cancer immunotherapy via combining oncolytic virotherapy with chemotherapy: recent advances.

    PubMed

    Simpson, Guy R; Relph, Kate; Harrington, Kevin; Melcher, Alan; Pandha, Hardev

    2016-01-01

    Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors. Similarly to oncolytic viruses, the benefits of chemotherapeutic agents may be that they induce systemic antitumor immunity through the induction of immunogenic cell death of cancer cells. Combining these two treatment modalities has to date resulted in significant potential in vitro and in vivo synergies through various mechanisms without any apparent additional toxicities. Chemotherapy has been and will continue to be integral to the management of advanced cancers. This review therefore focuses on the potential for a number of common cytotoxic agents to be combined with clinically relevant oncolytic viruses. In many cases, this combined approach has already advanced to the clinical trial arena.

  10. Maintenance Chemotherapy for Advanced Non–Small-Cell Lung Cancer: New Life for an Old Idea

    PubMed Central

    Gerber, David E.; Schiller, Joan H.

    2013-01-01

    Although well established for the treatment of certain hematologic malignancies, maintenance therapy has only recently become a treatment paradigm for advanced non–small-cell lung cancer. Maintenance therapy, which is designed to prolong a clinically favorable state after completion of a predefined number of induction chemotherapy cycles, has two principal paradigms. Continuation maintenance therapy entails the ongoing administration of a component of the initial chemotherapy regimen, generally the nonplatinum cytotoxic drug or a molecular targeted agent. With switch maintenance (also known as sequential therapy), a new and potentially non–cross-resistant agent is introduced immediately on completion of first-line chemotherapy. Potential rationales for maintenance therapy include increased exposure to effective therapies, decreasing chemotherapy resistance, optimizing efficacy of chemotherapeutic agents, antiangiogenic effects, and altering antitumor immunity. To date, switch maintenance therapy strategies with pemetrexed and erlotinib have demonstrated improved overall survival, resulting in US Food and Drug Administration approval for this indication. Recently, continuation maintenance with pemetrexed was found to prolong overall survival as well. Factors predicting benefit from maintenance chemotherapy include the degree of response to first-line therapy, performance status, the likelihood of receiving further therapy at the time of progression, and tumor histology and molecular characteristics. Several aspects of maintenance therapy have raised considerable debate in the thoracic oncology community, including clinical trial end points, the prevalence of second-line chemotherapy administration, the role of treatment-free intervals, quality of life, economic considerations, and whether progression-free survival is a worthy therapeutic goal in this disease setting. PMID:23401441

  11. Combining chemotherapy and targeted therapies in metastatic colorectal cancer

    PubMed Central

    Rodriguez, J; Zarate, R; Bandres, E; Viudez, A; Chopitea, A; García-Foncillas, J; Gil-Bazo, I

    2007-01-01

    Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, cetuximab and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer. PMID:17990352

  12. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  13. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  14. Selection of chemotherapy for patient treatment utilizing a radiometric versus a cloning system

    SciTech Connect

    Von Hoff, D.D.; Forseth, B.J.; Turner, J.N.; Clark, G.M.; Warfel, L.E.

    1986-01-01

    From the 1950s to the 1970s, a number of in vitro systems that measured inhibition of glucose metabolism were used to predict the responsiveness of patients' tumors to chemotherapy. In vitro-in vivo correlations were excellent, with true positive predictions ranging from 68% to 96% and true negative predictions of 95% to 100%. The radiometric system is a new in vitro technique that measures the conversion of 14C-glucose to 14CO2. The system already has been utilized to screen prospective new antineoplastic agents for cytotoxicity. The present study was undertaken to determine if the radiometric system might be used to predict correctly the responsiveness of an individual patient's tumor to single-agent or combination-agent chemotherapy. Fifty-six tumor specimens were divided and tested for drug sensitivity in the radiometric system and a conventional human tumor clonning system. Overall, there was a significant correlation between in vitro and in vivo results for the conventional cloning system (P = 0.03). However, there was no significant relationship between in vitro and in vivo results for the radiometric system. The radiometric system consistently failed to predict the tumor's clinical sensitivity to single agents. A radiometric system is not useful in predicting the responsiveness of a patient's tumor to single agent chemotherapy and is not a replacement for the more biologically attractive human tumor cloning system.

  15. Clinical roundtable monograph: New data in emerging treatment options for chemotherapy-induced nausea and vomiting.

    PubMed

    Morrow, Gary R; Navari, Rudolph M; Rugo, Hope S

    2014-03-01

    Chemotherapy-induced nausea and vomiting (CINV) has long been one of the most troublesome adverse effects of chemotherapy, leading to significant detriments in quality of life and functioning, increased economic costs, and, in some cases, the discontinuation of effective cancer therapy. The past 2 decades have witnessed a dramatic increase in the number of effective antiemetic agents, with the introduction of the serotonin (5-hydroxytryptamine [5-HT₃]) receptor antagonists (ondansetron, granisetron, and palonosetron), the neurokinin-1 (NK₁) receptor antagonists (aprepitant and fosaprepitant), and the identification of other agents that have demonstrated efficacy against CINV, including corticosteroids. These agents often provide excellent control of emesis. Nausea, however, has proven more intractable, particularly in the days after administration of chemotherapy. Newer antiemetic agents under study may provide additional CINV control, particularly against delayed nausea. New agents undergoing review by the US Food and Drug Administration for the prevention of CINV include the novel NK₁ receptor antagonist rolapitant and a fixed-dose combination consisting of the novel NK₁ receptor antagonist netupitant and palonosetron (NEPA). Adherence to clinical practice guidelines has been shown to significantly improve CINV control. As antiemetic therapy continues to evolve, it will be important for clinicians to stay informed of new developments and changes in guidelines.

  16. Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control

    PubMed Central

    Plataniotis, George A; Dale, Roger G

    2013-01-01

    The purpose of this study was to review the magnitude of contribution of chemotherapy (CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy (RCT) was used (how much higher local control rates are obtained with RCT compared to RT alone). Studies on radiotherapy (RT) and combined RCT, neo-adjuvant, concurrent, adjuvant or combinations, reported after 1990 were reviewed. The mean complete response (CR) rates were significantly higher for the RCT studies compared to RT-alone studies: 75.9% vs 64.4% (Wilcoxon rank-sum test, P = 0.001). Eleven of the included RCT studies involved 2-3 cycles of neo-adjuvant CT, in addition to concurrent RCT. The RCT studies included the one-phase type (where a full dose of RCT was given and then assessment of response and cystectomy for non-responders followed) and the two-phase types (where an assessment of response was undertaken after an initial RCT course, followed 6 wk later by a consolidation RCT for those patients with a CR). CR rates between the two subgroups of RCT studies were 79.6% (one phase) vs 71.6% (two-phase) (P = 0.015). The average achievable tumour control rates, with an acceptable rate of side effects have been around 70%, which may represent a plateau. Further increase in CR response rates demands for new chemotherapeutic agents, targeted therapies, or modified fractionation in various combinations. Quantification of RT and CT contribution to local control using radiobiological modelling in trial designs would enhance the potential for both improved outcomes and the estimation of the potential gain. PMID:24003352

  17. Cytotoxic chemotherapy: Still the mainstay of clinical practice for all subtypes metastatic breast cancer.

    PubMed

    Twelves, Chris; Jove, Maria; Gombos, Andrea; Awada, Ahmad

    2016-04-01

    Cytotoxic chemotherapy remains central to the treatment of all subtypes of metastatic breast cancer (MBC). We review evidence-based chemotherapy options for women with MBC after an anthracycline and a taxane including re-challenge with anthracycline or taxane, capecitabine, eribulin and ixabepilone as a single agent or combination with capecitabine (not approved in the EU); and the vinca alkaloid vinflunine as single agent or combined with either capecitabine/gemcitabine (also not approved EU or USA). Etirinotecan pegol, comprising irinotecan bound to polyethylene glycol by a biodegradable linker, is a new cytotoxic agent for patients with MBC that has achieved encouraging response rates in phase II studies; it has been further evaluated in the phase III BEACON trial. New cytotoxics should address novel targets or modes of delivery, achieve meaningful improvements in outcomes and seek to identify predictive biomarker(s).

  18. EGFR inhibitor and chemotherapy combinations for acquired TKI resistance in EGFR-mutant NSCLC models.

    PubMed

    Laurila, Niina; Koivunen, Jussi P

    2015-07-01

    Acquired resistance to EGFR TKIs is the most important limiting factor for treatment efficiency in EGFR-mutant NSCLC. Although the continuation of EGFR TKI beyond disease progression in combination with chemotherapy is often suggested as a strategy for treating acquired resistance, the optimal treatment sequence for EGFR TKI and chemotherapy is unknown. In the current work, NSCLC cell lines PC9ER, H1975 and HCC827GR, representing the acquired TKI resistance genotypes (T790M, cMET), were exposed to a chemotherapeutic agent, cisplatin or paclitaxel, in combination with EGFR TKIs (erlotinib, WZ4002) in vitro and analysed for cytotoxicity and apoptotic response. The result showed that all the combinations of EGFR TKIs with a chemotherapeutic agent tested had a synergistic effect on cytotoxicity and increased the apoptotic response. The sequences involving a chemotherapeutic agent concurrently with an EGFR TKI or preceding it were the most efficient strategies. Our in vitro models suggest that the combination of an EGFR TKI and chemotherapy is beneficial in cases of acquired EGFR TKI resistance. Furthermore, the sequence of chemotherapy followed by EGFR TKI is significantly more powerful than the reversed order, so that an intercalated approach is likely to be the most active strategy in clinical use and ought to be tested in a randomized clinical trial.

  19. mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy.

    PubMed

    Weiler, Markus; Blaes, Jonas; Pusch, Stefan; Sahm, Felix; Czabanka, Marcus; Luger, Sebastian; Bunse, Lukas; Solecki, Gergely; Eichwald, Viktoria; Jugold, Manfred; Hodecker, Sibylle; Osswald, Matthias; Meisner, Christoph; Hielscher, Thomas; Rübmann, Petra; Pfenning, Philipp-Niklas; Ronellenfitsch, Michael; Kempf, Tore; Schnölzer, Martina; Abdollahi, Amir; Lang, Florian; Bendszus, Martin; von Deimling, Andreas; Winkler, Frank; Weller, Michael; Vajkoczy, Peter; Platten, Michael; Wick, Wolfgang

    2014-01-07

    A hypoxic microenvironment induces resistance to alkylating agents by activating targets in the mammalian target of rapamycin (mTOR) pathway. The molecular mechanisms involved in this mTOR-mediated hypoxia-induced chemoresistance, however, are unclear. Here we identify the mTOR target N-myc downstream regulated gene 1 (NDRG1) as a key determinant of resistance toward alkylating chemotherapy, driven by hypoxia but also by therapeutic measures such as irradiation, corticosteroids, and chronic exposure to alkylating agents via distinct molecular routes involving hypoxia-inducible factor (HIF)-1alpha, p53, and the mTOR complex 2 (mTORC2)/serum glucocorticoid-induced protein kinase 1 (SGK1) pathway. Resistance toward alkylating chemotherapy but not radiotherapy was dependent on NDRG1 expression and activity. In posttreatment tumor tissue of patients with malignant gliomas, NDRG1 was induced and predictive of poor response to alkylating chemotherapy. On a molecular level, NDRG1 bound and stabilized methyltransferases, chiefly O(6)-methylguanine-DNA methyltransferase (MGMT), a key enzyme for resistance to alkylating agents in glioblastoma patients. In patients with glioblastoma, MGMT promoter methylation in tumor tissue was not more predictive for response to alkylating chemotherapy in patients who received concomitant corticosteroids.

  20. Interaction between Host Cells and Microbes in Chemotherapy-Induced Mucositis

    PubMed Central

    Stringer, Andrea M.

    2013-01-01

    Cancer patients receiving chemotherapy often develop mucositis as a direct result of their treatment. Recently, the intestinal microbiota has attracted significant attention in the investigation of the pathobiology of mucositis, with a number of studies investigating the effects of chemotherapeutic agents on the microbiota. With significant effects on the intestinal microbiota occurring following the administration of chemotherapy, there is now interest surrounding the downstream pathological effects that may be associated with the altered intestinal ecology. This review seeks to identify links between signalling pathways previously demonstrated to have a role in the development of mucositis, and the altered intestinal microbiota. PMID:23628721

  1. Beneficial effects of an anabolic steroid during cytotoxic chemotherapy for metastatic cancer.

    PubMed

    Spiers, A S; DeVita, S F; Allar, M J; Richards, S; Sedransk, N

    1981-01-01

    To investigate the effects of concurrent administration of an anabolic steroid upon hematopoiesis and metabolism in patients with cancer who were receiving cytotoxic chemotherapy, a randomized trial was conducted. Thirty-three evaluable patients received intensive multiple-agent chemotherapy: 17 received in addition nandrolone decanoate ("Deca-Durabolin"), 200 mg intramuscularly each week. The nandrolone-treated patients showed significantly better maintenance of hemoglobin concentrations and body weight, and a highly significant reduction in number of blood transfusions. Improved survival in the androgen-treated patients did not achieve significance. There were no differences in neutrophil or platelet counts or in tolerance of cytotoxic drugs. Toxicity from nandrolone therapy was minimal.

  2. Immunomodulation via Chemotherapy and Targeted Therapy: A New Paradigm in Breast Cancer Therapy?

    PubMed

    Stagg, John; Andre, Fabrice; Loi, Sherene

    2012-08-01

    Cytotoxic chemotherapy in the treatment of tumors has traditionally been thought to be immunosuppressive. Increasing evidence suggests the contrary and has introduced the concept of 'immunogenic' chemotherapy or, in other words, the concept that the innate and adaptive immune systems are critical in determining the long-term efficacy of some cytotoxic-based (and radiotherapy-based) regimens. The underlying mechanisms how these therapies can stimulate an antitumor immune response have been demonstrated recently. In this article, we review the background of this new paradigm and how combinations of traditional agents with the new immunotherapeutic therapies may significantly advance our treatment of breast cancer.

  3. Intracavitary chemotherapy (Gliadel) for recurrent esthesioneuroblastoma: case report and review of the literature.

    PubMed

    Park, Michael C; Weaver, Charles E; Donahue, John E; Sampath, Prakash

    2006-03-01

    Esthesioneuroblastoma is an uncommon malignancy of the nasal vault with a treatment regimen consisting of surgical resection followed by radiotherapy for primary lesions and addition of chemotherapy for patients with advanced, recurrent or metastatic lesions. We report a case of a 39-year-old female with a history of esthesioneuroblastoma, previously treated with resection, radiation and chemotherapy, presenting with a recurrent disease that was successfully treated with re-resection and placement of Gliadel) wafers in the surgical resection cavity. The novel option of controlled-release and local delivery of a chemotherapeutic agent for treatment of recurrent esthesioneuroblastoma should be recognized and considered.

  4. Fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting.

    PubMed

    Ruhlmann, Christina H; Herrstedt, Jørn

    2012-02-01

    For patients receiving cancer chemotherapy, the ongoing development of antiemetic treatment is of significant importance. Patients consider nausea and vomiting among the most distressing symptoms of chemotherapy, and as new antiemetics have been very successful in prevention of vomiting, agents effective against nausea have become one of the major unmet needs. The neurokinin (NK)(1) receptor antagonist aprepitant potentiates the antiemetic efficacy of the combination of a serotonin receptor antagonist and a corticosteroid. Fosaprepitant (intravenous prodrug of aprepitant) given as a single intravenous dose of 150 mg can replace the aprepitant 3-day oral regimen. This article focuses on the development and clinical application of fosaprepitant.

  5. Ewing sarcoma/primitive neuroectodermal tumor of the kidney treated with chemotherapy including ifosfamide.

    PubMed

    Yoshihara, Hiroki; Kamiya, Takahiro; Hosoya, Yosuke; Hasegawa, Daisuke; Ogawa, Chitose; Asanuma, Hiroshi; Mizuno, Ryuichi; Hosoya, Ryota; Manabe, Atsushi

    2016-08-01

    Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the kidney is extremely rare, and is usually diagnosed after nephrectomy without neoadjuvant chemotherapy. Although ifosfamide and etoposide improve survival to a great extent in ES/PNET, the use of nephrotoxic agent, particularly ifosfamide, is a concern after nephrectomy. We describe the case of a 14-year-old female patient with abdominal mass who was diagnosed with ES/PNET of the right kidney after nephrectomy. Adjuvant chemotherapy including ifosfamide and etoposide were given. The estimated glomerular filtration rate decreased to 75% after the end of therapy. There was no evidence of recurrence 70 months after initial diagnosis.

  6. Chemotherapy in Children with Head and Neck Cancers: Perspectives and Review of Current Therapies.

    PubMed

    Choi, Daniel K; Schmidt, Mary Lou

    2016-02-01

    Cancers of the head and neck in children represent a heterogeneous group of malignancies requiring a variety of treatment modalities. In many instances of childhood head and neck cancers, chemotherapy will be required for treatment, often in conjunction with surgery and/or radiation therapy. Chemotherapy in children with head and neck cancers poses unique challenges in terms of immediate as well as long-term toxicities. This article focuses on the common chemotherapeutic agents, with a particular focus on early and late effects, used in the treatment of children with head and neck cancers.

  7. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy

    PubMed Central

    McPartland, Sarah; Detelich, Danielle; Saif, Muhammad Wasif

    2016-01-01

    Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options. PMID:26941983

  8. Gut microbiota modulation of chemotherapy efficacy and toxicity.

    PubMed

    Alexander, James L; Wilson, Ian D; Teare, Julian; Marchesi, Julian R; Nicholson, Jeremy K; Kinross, James M

    2017-06-01

    Evidence is growing that the gut microbiota modulates the host response to chemotherapeutic drugs, with three main clinical outcomes: facilitation of drug efficacy; abrogation and compromise of anticancer effects; and mediation of toxicity. The implication is that gut microbiota are critical to the development of personalized cancer treatment strategies and, therefore, a greater insight into prokaryotic co-metabolism of chemotherapeutic drugs is now required. This thinking is based on evidence from human, animal and in vitro studies that gut bacteria are intimately linked to the pharmacological effects of chemotherapies (5-fluorouracil, cyclophosphamide, irinotecan, oxaliplatin, gemcitabine, methotrexate) and novel targeted immunotherapies such as anti-PD-L1 and anti-CLTA-4 therapies. The gut microbiota modulate these agents through key mechanisms, structured as the 'TIMER' mechanistic framework: Translocation, Immunomodulation, Metabolism, Enzymatic degradation, and Reduced diversity and ecological variation. The gut microbiota can now, therefore, be targeted to improve efficacy and reduce the toxicity of current chemotherapy agents. In this Review, we outline the implications of pharmacomicrobiomics in cancer therapeutics and define how the microbiota might be modified in clinical practice to improve efficacy and reduce the toxic burden of these compounds.

  9. Chemotherapy-induced peripheral neuropathy: a review of recent findings.

    PubMed

    Kim, Peggy Y; Johnson, Carrie E

    2017-10-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common, frequently chronic condition characterized by pain and decreased function. Given the growing number of cancer survivors and an increasing recognition of opioid therapy limitations, there is a need for critical analysis of the literature in directing an informed and thoughtful approach for the management of painful CIPN. A PubMed search for 'chemotherapy-induced peripheral neuropathy AND pain' identifies 259 publications between 1 January 2016 and 31 March 2017. Based on review of this literature, we aim to present a clinically relevant update of painful CIPN. Notably, the use of duloxetine as a first-line agent in treatment of CIPN is confirmed. Moreover, clinical trials focus on nonpharmacologic strategies for managing painful CIPN. Despite the volume of recent publications, there are limited preventive or therapeutic strategies for CIPN supported by high-level evidence. Duloxetine remains the only pharmacologic agent with demonstrated benefit; its clinical use should be routinely considered. Moving forward, nonopioid analgesic therapies will likely play an increasing role in CIPN treatment, but further research is necessary to confirm their utility. Promising therapies include vitamin B12 supplementation, physical therapy, and various forms of neuromodulation.

  10. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    MedlinePlus

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. Then I got used ... uncovered.” Questions other people have asked: Why does hair fall out? Chemotherapy can harm the cells that ...

  11. [Chemotherapy-induced stomatitis and diarrhea].

    PubMed

    Kadowaki, Shigenori; Yamaguchi, Kensei

    2011-11-01

    Chemotherapy-induced mucositis is a clinically important and sometimes dose-limiting toxicity of cancer treatment, including standard-dose chemotherapy, high-dose chemotherapy and chemoradiotherapy. Consequently, dose reductions or treatment delays resulting from mucositis may impair treatment effectiveness. Symptoms are oral mucositis, dysphagia, abdominal pain and diarrhea, depending on the affected site. Although the underlying pathobiology of oral mucositis has been considerably elucidated over the past decade, there are few interventions for the prevention or treatment validated by randomized trials. The most commonly accepted intervention is basic oral care. Diarrhea is most common in patients treated with irinotecan and in some cases, life-threatening. No definitive interventions for the prevention of diarrhea exist, but there is evidence that loperamide and octreotide are effective for chemotherapy-induced diarrhea. In future, there is a need for well designed trials, preferably including a placebo or no treatment control, validating more effective interventions for managing chemotherapy- induced mucositis.

  12. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  13. [Genomic markers and anticancer chemotherapy].

    PubMed

    Nishiyama, Masahiko

    2008-02-01

    Worldwide research on the human genome exerts a major impact on medical science. The growing evidence that genetic polymorphisms in the metabolism, the disposition, and the targets of drugs can have an even greater influence on the efficacy and the toxicity led to the creation of a novel chemotherapeutic strategy, personalized medicine. Much effort has been directed toward identifying the indicators of individual response to drugs, and these studies have provided a variety of potent predictive markers of individual drug response, which include some significant markers in clinical practice with sufficient evidence. Personalized medicine based on the response prediction using genomic marker is increasingly being recognized as a practical treatment approach in cancer chemotherapy, and to be indispensable when molecular targeted drugs are involved in the therapy. Even so, the ingenious and intricate mechanism of individual drug response creates obstacles in predicting chemotherapeutic response: Multiple factors are involved in the mechanisms, and key factors for drug response vary significantly among individuals. DNA chip technology enables us to overview a huge number of gene expressions simultaneously, but gene expression profiles of drug sensitivity vary considerably even for the same drug, which shows the limited value of a static microarray-expression profile as a marker aimed at individualizing patient therapy. Selection of a set of truly significant genomic markers and understanding of their interplay are of key importance in prediction of individual response to drug therapies. Challenges to such biological complexity are now started to identify a better genomic marker. The contribution of genomic marker research to anticancer chemotherapy and problems of the day were reviewed.

  14. Trace Elements and Chemotherapy Sensitivity.

    PubMed

    Liu, Zhihui; Yang, Weiping; Long, Gang; Wei, Changyuan

    2016-10-01

    Trace elements might be associated with the development of hepatocellular carcinoma (HCC) and the efficacy of chemotherapy against HCC. Therefore, this study aimed to explore the association between trace elements and efficacy of chemotherapy in patients with HCC. Cancer, cancer-adjacent, and cancer-free tissues were collected intraoperatively from 55 patients with HCC between January 2001 and April 2004 at the Affiliated Tumor Hospital of Guangxi Medical University in Guangxi (China), a high HCC incidence area in the world. Trace element levels were analyzed by atomic absorption spectrophotometry. In vitro sensitivity of cancer cells to five chemotherapeutic drugs (5-fluorouracil, doxorubicin, cisplatin, carboplatin, and mitomycin) was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in cancer cells from 32 patients. Zinc, copper, manganese, and selenium levels had the same gradient distribution in different liver tissues: cancer < cancer-adjacent < cancer-free tissues. Copper levels of cancer tissues were negatively correlated with body weight (r = -0.278, P = 0.027), while manganese and selenium levels were negatively correlated with age (r = -0.297, P = 0.015; r = -0.285, P = 0.018, respectively). Simple correlation analyses revealed that the carboplatin sensitivity was negatively correlated with selenium levels of cancer tissues, while doxorubicin sensitivity was negatively correlated with manganese levels (r = -0.497, P = 0.004). Partial correlation analyses showed that doxorubicin sensitivity only was negatively correlated with manganese levels (r = -0.450, P = 0.014). These results suggest that the selenium and manganese content in primary HCC tissues could influence the response of the HCC cells to carboplatin and doxorubicin. These preliminary results provide a basis for future studies.

  15. [Microorganism test systems and antibiograms useful for the proper use of antibacterial agents].

    PubMed

    Takahashi, Shunji

    2010-07-01

    Antimicrobial agents are used for the accurate diagnosis of infectious diseases and effective implementation of antibacterial chemotherapy. The role of microbiological technologists is to provide data from microorganism tests useful for rapid infection treatment. Gram strain can be used to observe microorganisms and neutrophils from specimens of a patient. It is also possible to estimate the kinds of microorganism. If bacterial infectious disease is negative, there is no need for antibacterial chemotherapy. The applied dose of antibacterial agents is different in every hospital. Also, there is a difference in the percentage antibacterial agent susceptibility of isolates. Antibiograms must be created to investigate local factors. For empiric therapy, antibiograms are useful when choosing antibacterial agents showing marked efficacy against the clinical isolate. Microorganism test systems which are useful for the proper use of antibacterial agents are necessary to facilitate safe antibacterial chemotherapy and prevent the development of resistant bacteria. We report a microorganism test system employed at the Sapporo City General Hospital.

  16. Children's acceptance and tolerance of chlorhexidine and benzydamine oral rinses in the treatment of chemotherapy-induced oropharyngeal mucositis.

    PubMed

    Cheng, K K F

    2004-12-01

    Oral care is of great importance in the prevention of chemotherapy-induced oropharyngeal mucositis. Although considerable attention has been given in improving oral care practices, patients' acceptance and tolerance of oral rinses is a continuing problem in oral care. A randomized crossover design was used to determine the relative acceptability and tolerability of chlorhexidine and benzydamine oral rinse agents in children receiving chemotherapy. At the end of the study, each subject was asked to compare these two agents in relation to stinging and taste, as well as his/her perception in reducing mucositis. Thirty-four children aged 6-17 years completed two courses of chemotherapy during which they alternately practiced oral care using chlorhexidine then benzydamine or benzydamine then chlorhexidine. All of the children tolerated the agents well and continued with rinsing throughout the study. Only a few children had to resort to diluting the agents with normal saline or water. Fifty-nine percent of children reported that the stinging associated with benzydamine was more accepted than chlorhexidine. The taste of both these agents was accepted by 50% of children. Approximately 60% of children reported that chlorhexidine was more helpful than benzydamine in reducing mucositis. About 47% and 50% of them preferred chlorhexidine and benzydamine in their subsequent chemotherapy, respectively. In conclusion, chlorhexidine and benzydamine are acceptable and well-tolerated by children over the age 6 years old.

  17. Mitochondrial Transcription Factor A and Mitochondrial Genome as Molecular Targets for Cisplatin-Based Cancer Chemotherapy.

    PubMed

    Kohno, Kimitoshi; Wang, Ke-Yong; Takahashi, Mayu; Kurita, Tomoko; Yoshida, Yoichiro; Hirakawa, Masakazu; Harada, Yoshikazu; Kuma, Akihiro; Izumi, Hiroto; Matsumoto, Shinji

    2015-08-20

    Mitochondria are important cellular organelles that function as control centers of the energy supply for highly proliferative cancer cells and regulate apoptosis after cancer chemotherapy. Cisplatin is one of the most important chemotherapeutic agents and a key drug in therapeutic regimens for a broad range of solid tumors. Cisplatin may directly interact with mitochondria, which can induce apoptosis. The direct interactions between cisplatin and mitochondria may account for our understanding of the clinical activity of cisplatin and development of resistance. However, the basis for the roles of mitochondria under treatment with chemotherapy is poorly understood. In this review, we present novel aspects regarding the unique characteristics of the mitochondrial genome in relation to the use of platinum-based chemotherapy and describe our recent work demonstrating the importance of the mitochondrial transcription factor A (mtTFA) expression in cancer cells.

  18. Gene therapy enhances chemotherapy tolerance and efficacy in glioblastoma patients.

    PubMed

    Adair, Jennifer E; Johnston, Sandra K; Mrugala, Maciej M; Beard, Brian C; Guyman, Laura A; Baldock, Anne L; Bridge, Carly A; Hawkins-Daarud, Andrea; Gori, Jennifer L; Born, Donald E; Gonzalez-Cuyar, Luis F; Silbergeld, Daniel L; Rockne, Russell C; Storer, Barry E; Rockhill, Jason K; Swanson, Kristin R; Kiem, Hans-Peter

    2014-09-01

    Temozolomide (TMZ) is one of the most potent chemotherapy agents for the treatment of glioblastoma. Unfortunately, almost half of glioblastoma tumors are TMZ resistant due to overexpression of methylguanine methyltransferase (MGMT(hi)). Coadministration of O6-benzylguanine (O6BG) can restore TMZ sensitivity, but causes off-target myelosuppression. Here, we conducted a prospective clinical trial to test whether gene therapy to confer O6BG resistance in hematopoietic stem cells (HSCs) improves chemotherapy tolerance and outcome. We enrolled 7 newly diagnosed glioblastoma patients with MGMT(hi) tumors. Patients received autologous gene-modified HSCs following single-agent carmustine administration. After hematopoietic recovery, patients underwent O6BG/TMZ chemotherapy in 28-day cycles. Serial blood samples and tumor images were collected throughout the study. Chemotherapy tolerance was determined by the observed myelosuppression and recovery following each cycle. Patient-specific biomathematical modeling of tumor growth was performed. Progression-free survival (PFS) and overall survival (OS) were also evaluated. Gene therapy permitted a significant increase in the mean number of tolerated O6BG/TMZ cycles (4.4 cycles per patient, P < 0.05) compared with historical controls without gene therapy (n = 7 patients, 1.7 cycles per patient). One patient tolerated an unprecedented 9 cycles and demonstrated long-term PFS without additional therapy. Overall, we observed a median PFS of 9 (range 3.5-57+) months and OS of 20 (range 13-57+) months. Furthermore, biomathematical modeling revealed markedly delayed tumor growth at lower cumulative TMZ doses in study patients compared with patients that received standard TMZ regimens without O6BG. These data support further development of chemoprotective gene therapy in combination with O6BG and TMZ for the treatment of glioblastoma and potentially other tumors with overexpression of MGMT. Clinicaltrials.gov NCT00669669. R01CA114218, R

  19. The Association of Chemotherapy-Induced Peripheral Neuropathy Symptoms and the Risk of Falling.

    PubMed

    Kolb, Noah A; Smith, A Gordon; Singleton, J Robinson; Beck, Susan L; Stoddard, Gregory J; Brown, Summer; Mooney, Kathi

    2016-07-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic chemotherapy resulting in pain, sensory loss, and decreased quality of life. Few studies have prospectively examined the relationship between sensory neuropathy symptoms, falls, and fall-related injuries for patients receiving neurotoxic chemotherapy. To determine the association between the symptoms of CIPN and the risk of falls for patients receiving neurotoxic chemotherapy. In this secondary analysis of a prospective study, 116 patients with breast, ovarian, or lung cancer who were beginning neurotoxic chemotherapy with a taxane or platinum agent were recruited from oncology clinics. These patients would call a novel automated telephone system daily for 1 full course of chemotherapy. The telephone system (SymptomCare@Home) used a series of relevant CIPN questions to track symptoms on a 0 to 10 ordinal scale and contained a questionnaire about falls. Those reporting a numbness and tingling severity score of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared with those patients who did not. Data analysis was performed in November 2015. Chemotherapy with a neurotoxic taxane or platinum agent. Patient-reported falls or near falls and fall-related injuries. The hypothesis was generated after data collection but prior to data analysis. Of the 116 patients who started neurotoxic chemotherapy (mean [SD] age was 55.5 [11.9] years, and 109 [94.0%] were female), 32 met the predetermined criteria for CIPN symptoms. The mean duration of follow-up was 62 days, with 51 telephone calls completed per participant. Seventy-four falls or near falls were reported. The participants with CIPN symptoms were nearly 3 times more likely to report a fall or near fall than the participants without CIPN symptoms (hazard ratio, 2.67 [95% CI, 1.62-4.41]; P < .001). The participants with CIPN symptoms were more likely than the participants without

  20. Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability.

    PubMed

    Zinzani, Pier Luigi

    2006-09-01

    Follicular lymphoma (FL) is typically characterized by repeated remissions and relapses, and many patients receive a number of therapeutic interventions during their disease course. Although treatment options are evolving rapidly, stem cell transplantation offers a potentially favorable impact on survival. In general, many patients with FL are not eligible for this approach by virtue of age and/or comorbid disease. Salvage chemotherapy consequently remains the mainstay of treatment, being individualized according to disease and patient characteristics, goals of therapy, and patient preference. Many of the cytotoxic agents used in relapsed FL are highly myelotoxic, leading to significant morbidity and mortality, including febrile neutropenia, hemorrhage, and impaired quality of life. Nausea and vomiting can also be problematic, particularly with regimens incorporating carmustine, cisplatin, and high-dose cyclophosphamide. Other acute toxicities include mucositis, alopecia, extravasation injuries, and neurotoxicity. Late toxicities can also occur, sometimes months or even years after the administration of antineoplastic agents. Acute myeloid leukemias, myelodysplastic syndromes, or solid tumors can occur after chemotherapy with alkylating agents. The cardiotoxic profile of anthracycline antibiotics is well recognized, and several agents, including carmustine and cyclophosphamide, can cause lung injury. Persistent neurotoxicity, nephrotoxicity, ototoxicity, and vascular toxicity have also been reported in association with chemotherapeutic agents used in patients with relapsed FL. Novel therapeutic strategies might allow patients to achieve longer remissions, potentially reducing lifetime exposure to repeated cycles of chemotherapy and their attendant toxicities. These could include the use of more efficient preparative and purging approaches in the transplantation setting or the administration of rituximab maintenance therapy after (immuno) chemotherapy induction or

  1. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  2. Pharmacodynamic model for chemotherapy-induced anemia in rats.

    PubMed

    Woo, Sukyung; Krzyzanski, Wojciech; Jusko, William J

    2008-06-01

    Anticancer agents often cause bone marrow toxicity resulting in progressive anemia which may influence the therapeutic effects of erythropoietic-stimulating agents. The objective of this study was to develop a pharmacodynamic (PD) model to describe chemotherapy-induced anemia in rats. Anemia was induced in male Wistar rats with a single intravenous (i.v.) injection of 60 mg/kg carboplatin. Hematological responses including reticulocytes, red blood cells (RBC), hemoglobin, and endogenous rat erythropoietin (EPO) were measured for up to 4 weeks. A catenary, lifespan-based, indirect response model served as a basic PD model to represent erythroid cellular populations in the bone marrow and blood involved in erythropoiesis. The model assumed that actively proliferating progenitor cells in the bone marrow are sensitive to anti-cancer agents and subject to an irreversible removal process. The removal rate of the target cells is proportional to drug activity concentrations and the cell numbers. An additional RBC loss from the circulation resulting from thrombocytopenia was described by a first-order process. The turnover process of rat EPO and EPO-mediated feedback inhibition mechanism regulated by hemoglobin changes were incorporated. Reticulocyte counts decreased rapidly and reached a nadir by day 3 after administration of carboplatin and returned to the baseline by day 13. This was followed by a gradual increase and the rebound peak occurred at about day 15. The hemoglobin nadir was approximately 9 g/dl observed at about 11-13 days compared to its normal value of 13 g/dl and hemoglobin returned to the baseline by day 30. The increase in endogenous rat EPO mirrored inversely hemoglobin changes and the maximum increase was observed soon after the hemoglobin nadir. The carboplatin-treated rats exhibited progressive anemia. The proposed model adequately described the time course of hematological changes after carboplatin in rats and can be a useful tool to explore

  3. Liver resection for advanced or aggressive colorectal cancer metastases in the era of effective chemotherapy: a review.

    PubMed

    Tanaka, Kuniya; Ichikawa, Yasushi; Endo, Itaru

    2011-10-01

    Liver surgery has been known to cure metastatic colorectal cancer in a small proportion of patients. However, advances in procedural technique and chemotherapy now allow more patients to have safe, potentially curative surgery. Here we review surgery for unresectable colorectal liver metastases using an expert multidisciplinary approach. With multidisciplinary management of patients with effective chemotherapy that can downstage metastases, more patients with previously inoperable disease can benefit from surgery. Portal vein embolization results in hypertrophy of the future liver remnant; on occasions, combining embolization with staged liver resection permits potentially curative surgery for patients previously unable to survive resection. However, increasing use of chemotherapy has raised awareness of potential hepatotoxicity and other deleterious effects of cytotoxic agents. Prolonged prehepatectomy chemotherapy therefore can reduce resectability even using a 2-stage procedure. Suitable timing of surgery for unresectable liver metastases during chemotherapy is critical. Because of advances in chemotherapy, colorectal cancer, like ovarian cancer, can now show survival benefit from maximum surgical debulking. Benefit from such maximum hepatic debulking surgery for metastatic colorectal disease is uncertain, but likely. Surgery in isolation may be approaching technical limits, but is now likely to help more patients because of the success of complementary strategies, particularly newer chemotherapy and targeted therapy. Expert individualized multidisciplinary treatment planning and problem-solving is essential.

  4. Virtual Reality: A Distraction Intervention for Chemotherapy

    PubMed Central

    Schneider, Susan M.; Hood, Linda E.

    2007-01-01

    Purpose/Objectives To explore virtual reality (VR) as a distraction intervention to relieve symptom distress in adults receiving chemotherapy treatments for breast, colon, and lung cancer. Design Crossover design in which participants served as their own control. Setting Outpatient clinic at a comprehensive cancer center in the southeastern United States. Sample 123 adults receiving initial chemotherapy treatments. Methods Participants were randomly assigned to receive the VR distraction intervention during one chemotherapy treatment and then received no intervention (control) during an alternate matched chemotherapy treatment. The Adapted Symptom Distress Scale–2, Revised Piper Fatigue Scale, and State Anxiety Inventory were used to measure symptom distress. The Presence Questionnaire and an open-ended questionnaire were used to evaluate the subjects’ VR experience. The influence of type of cancer, age, and gender on symptom outcomes was explored. Mixed models were used to test for differences in levels of symptom distress. Main Research Variables Virtual reality and symptom distress. Findings Patients had an altered perception of time (p < 0.001) when using VR, which validates the distracting capacity of the intervention. Evaluation of the intervention indicated that patients believed the head-mounted device was easy to use, they experienced no cybersickness, and 82% would use VR again. However, analysis demonstrated no significant differences in symptom distress immediately or two days following chemotherapy treatments. Conclusions Patients stated that using VR made the treatment seem shorter and that chemotherapy treatments with VR were better than treatments without the distraction intervention. However, positive experiences did not result in a decrease in symptom distress. The findings support the idea that using VR can help to make chemotherapy treatments more tolerable, but clinicians should not assume that use of VR will improve chemotherapy

  5. Chemotherapy drug handling in first opinion small animal veterinary practices in the United Kingdom: results of a questionnaire survey.

    PubMed

    Edery, E G

    2017-03-07

    To investigate how first opinion small animal veterinary surgeons in the UK handled chemotherapeutic agents, a questionnaire was distributed at the 2014 British Small Animal Veterinary Association congress and by internet. Chemotherapy was regularly offered by 70.4 per cent of the respondents. Gold standards defined according to available guidelines for safe handling of antineoplastic drugs were poorly followed by general practitioners with only 2 per cent of respondents complying with all of them. Dedicated facilities for preparation and administration of cytotoxic drugs were variably available among participants. The level of training of staff indirectly involved in handling chemotherapy was appropriate in less than 50 per cent of practices. No association was found between demographic characteristics of the sampled population and the decision to perform chemotherapy. The results of this study raise concerns about the safety of the veterinary staff in first opinion practices involved in handling chemotherapy.

  6. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

    PubMed

    Navari, Rudolph M; Nagy, Cindy K; Gray, Sarah E

    2013-06-01

    Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis. A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable. During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities. Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.

  7. Dose-Dense Chemotherapy in Nonmetastatic Breast Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Bonilla, Luisa; Ben-Aharon, Irit; Vidal, Liat; Gafter-Gvili, Anat; Leibovici, Leonard

    2010-01-01

    Background Dose-dense chemotherapy has become a mainstay regimen in the adjuvant setting for women with high-risk breast cancer. We performed a systematic review and meta-analysis of the existing data from randomized controlled trials regarding the efficacy and toxicity of the dose-dense chemotherapy approach in nonmetastatic breast cancer. Methods Randomized controlled trials that compared a dose-dense chemotherapy protocol with a standard chemotherapy schedule in the neoadjuvant or adjuvant setting in adult women older than 18 years with breast cancer were identified by searching The Cochrane Cancer Network register of trials, The Cochrane Library, and LILACS and MEDLINE databases (from January 1966 to January 2010). Hazard ratios (HRs) of death and recurrence and relative risks of adverse events were estimated and pooled. All statistical tests were two-sided. Results Ten trials met the inclusion criteria and were classified into two categories based on trial methodology. Three trials enrolling 3337 patients compared dose-dense chemotherapy with a conventional chemotherapy schedule (similar agents). Patients who received dose-dense chemotherapy had better overall survival (HR of death = 0.84, 95% confidence interval [CI] = 0.72 to 0.98, P = .03) and better disease-free survival (HR of recurrence or death = 0.83, 95% CI = 0.73 to 0.94, P = .005) than those on the conventional schedule. No benefit was observed in patients with hormone receptor–positive tumors. Seven trials enrolling 8652 patients compared dose-dense chemotherapy with regimens that use standard intervals but with different agents and/or dosages in the treatment arms. Similar results were obtained for these trials with respect to overall survival (HR of death = 0.85, 95% CI = 0.75 to 0.96, P = .01) and disease-free survival (HR of recurrence or death = 0.81, 95% CI = 0.73 to 0.88, P < .001). The rate of nonhematological adverse events was higher in the dose-dense chemotherapy arms than in the

  8. Overview, prevention and management of chemotherapy extravasation

    PubMed Central

    Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

    2016-01-01

    Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused. PMID:26862492

  9. A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients.

    PubMed

    Chung, Suyoun; Low, Siew-Kee; Zembutsu, Hitoshi; Takahashi, Atsushi; Kubo, Michiaki; Sasa, Mitsunori; Nakamura, Yusuke

    2013-01-01

    Chemotherapy-induced alopecia is one of the most common adverse events caused by conventional cytotoxic chemotherapy, yet there has been very little progress in the prevention or treatment of this side effect. Although this is not a life-threatening event, alopecia is very psychologically difficult for many women to manage. In order to improve the quality of life for these women, it is important to elucidate the molecular mechanisms of chemotherapy-induced alopecia and develop ways to effectively prevent and/or treat it. To identify the genetic risk factors associated with chemotherapy-induced alopecia, we conducted a genome-wide association study (GWAS) using DNA samples from breast cancer patients who were treated with chemotherapy. We performed a case-control association study of 303 individuals who developed grade 2 alopecia, and compared them with 880 breast cancer patients who did not show hair loss after being treated with conventional chemotherapy. In addition, we separately analyzed a subset of patients who received specific combination therapies by GWASs and applied the weighted genetic risk scoring (wGRS) system to investigate the cumulative effects of the associated SNPs. We identified an SNP significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4 (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 × 10(-9), OR = 3.71) and detected several SNPs that showed some suggestive associations by subgroup analyses. We also classified patients into four groups on the basis of wGRS analysis and found that patients who classified in the highest risk group showed 443 times higher risk of antimicrotubule agents-induced alopecia than the lowest risk group. Our study suggests several associated genes and should shed some light on the molecular mechanism of alopecia in chemotherapy-treated breast cancer patients and hopefully will contribute to development of interventions that will improve the quality of life (QOL) of cancer

  10. p53-Based Strategy to Reduce Hematological Toxicity of Chemotherapy: A Proof of Principle Study

    PubMed Central

    Ha, Chul S.; Michalek, Joel E.; Elledge, Richard; Kelly, Kevin R.; Ganapathy, Suthakar; Su, Hang; Jenkins, Carol A.; Argiris, Athanassios; Swords, Ronan; Eng, Tony Y.; Karnad, Anand; Crownover, Richard L.; Swanson, Gregory P.; Goros, Martin; Pollock, Brad H.; Yuan, Zhi-Min

    2015-01-01

    P53 activation is a primary mechanism underlying pathological responses to DNA-damaging agents such as chemotherapy and radiotherapy. Our recent animal studies showed that low dose arsenic (LDA)-induced transient p53 inhibition selectively protected normal tissues from chemotherapy-induced toxicity. Study objectives were to: 1) define the lowest safe dose of arsenic trioxide that transiently blocks p53 activation in patients and 2) assess the potential of LDA to decrease hematological toxicity from chemotherapy. Patients scheduled to receive minimum 4 cycles of myelosuppressive chemotherapy were eligible. For objective 1, dose escalation of LDA started at 0.005mg/kg/day for 3 days. This dose satisfied objective 1 and was administered before chemotherapy cycles 2, 4 and 6 for objective 2. P53 level in peripheral lymphocytes was measured on day 1 of each cycle by ELISA assay. Chemotherapy cycles 1, 3, and 5 served as the baseline for the subsequent cycles of 2, 4 and 6 respectively. If p53 level for the subsequent cycle was lower (or higher) than the baseline cycle, p53 was defined as “suppressed” (or “activated”) for the pair of cycles. Repeated measures linear models of CBC in terms of day, cycle, p53 activity and interaction terms were used. Twenty-six patients treated with 3 week cycle regimens form the base of analyses. The mean white blood cell, hemoglobin and absolute neutrophil counts were significantly higher in the “suppressed” relative to the “activated” group. These data support the proof of principle that suppression of p53 could lead to protection of bone marrow in patients receiving chemotherapy. PMID:26440706

  11. Characteristics of pediatric chemotherapy medication errors in a national error reporting database.

    PubMed

    Rinke, Michael L; Shore, Andrew D; Morlock, Laura; Hicks, Rodney W; Miller, Marlene R

    2007-07-01

    Little is known regarding chemotherapy medication errors in pediatrics despite studies suggesting high rates of overall pediatric medication errors. In this study, the authors examined patterns in pediatric chemotherapy errors. The authors queried the United States Pharmacopeia MEDMARX database, a national, voluntary, Internet-accessible error reporting system, for all error reports from 1999 through 2004 that involved chemotherapy medications and patients aged <18 years. Of the 310 pediatric chemotherapy error reports, 85% reached the patient, and 15.6% required additional patient monitoring or therapeutic intervention. Forty-eight percent of errors originated in the administering phase of medication delivery, and 30% originated in the drug-dispensing phase. Of the 387 medications cited, 39.5% were antimetabolites, 14.0% were alkylating agents, 9.3% were anthracyclines, and 9.3% were topoisomerase inhibitors. The most commonly involved chemotherapeutic agents were methotrexate (15.3%), cytarabine (12.1%), and etoposide (8.3%). The most common error types were improper dose/quantity (22.9% of 327 cited error types), wrong time (22.6%), omission error (14.1%), and wrong administration technique/wrong route (12.2%). The most common error causes were performance deficit (41.3% of 547 cited error causes), equipment and medication delivery devices (12.4%), communication (8.8%), knowledge deficit (6.8%), and written order errors (5.5%). Four of the 5 most serious errors occurred at community hospitals. Pediatric chemotherapy errors often reached the patient, potentially were harmful, and differed in quality between outpatient and inpatient areas. This study indicated which chemotherapeutic agents most often were involved in errors and that administering errors were common. Investigation is needed regarding targeted medication administration safeguards for these high-risk medications. Copyright (c) 2007 American Cancer Society.

  12. Pre-operative chemotherapy for colorectal cancer liver metastases: an update of recent clinical trials.

    PubMed

    Nasti, G; Ottaiano, A; Berretta, M; Delrio, P; Izzo, F; Cassata, A; Romano, C; Facchini, G; Scala, D; Mastro, A; Romano, G; Perri, F; Iaffaioli, R V

    2010-07-01

    The standard treatment of CRC patients with hepatic metastases is systemic chemotherapy; however, 5-year survival is disappointingly poor despite recent advances. On the other hand, in patients who undergo immediate radical surgical resection of hepatic metastases, 5-year survival reaches 30-40%. Unfortunately, only 15-20% of patients with hepatic metastases are initially eligible for a radical surgical approach. The majority of patients undergoing liver resection relapse after surgery. For this reason, new onco-surgery approaches have been investigated in recent years and the addition of biological agents to chemotherapy, such as bevacizumab and cetuximab, and the improvements of surgical techniques have opened a new scenario in the management of colorectal liver metastases. Recently, the EORTC trial has demonstrated that perioperative chemotherapy (Folfox regimen) is feasible and improves progression-free survival in patients with resectable liver metastases. Chemotherapy and surgery can finally collaborate. In the unresectable setting, the association of chemotherapy with bevacizumab and cetuximab is particularly promising in improving resectability rate. In particular, K-RAS is a molecular response predictive factor that could be particularly useful in selecting the best treatment option in patients with unresectable liver disease.

  13. Modeling Chemotherapy-Induced Hair Loss: From Experimental Propositions toward Clinical Reality.

    PubMed

    Botchkarev, Vladimir A; Sharov, Andrey A

    2016-03-01

    Chemotherapy-induced hair loss is one of the most devastating side effects of cancer treatment. To study the effects of chemotherapeutic agents on the hair follicle, a number of experimental models have been proposed. Yoon et al. report that transplantation of human scalp hair follicles onto chemotherapy-treated immunodeficient mice serves as an excellent in vivo model for chemotherapy-induced hair loss. Yoon et al. demonstrate that (i) the response of human hair follicles grafted onto immunodeficient mice to cyclophosphamide resembles the key features of the chemotherapy-induced hair loss seen in patients with cancer and (ii) this human in vivo model for chemotherapy-induced hair loss is closer to clinical reality than to any earlier models. Undoubtedly, this model will serve as a valuable tool for analyses of the mechanisms that underlie this devastating side effect of anti-cancer therapy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Current pharmacotherapy for chemotherapy-induced nausea and vomiting in cancer patients.

    PubMed

    Janelsins, Michelle C; Tejani, Mohamedtaki A; Kamen, Charles; Peoples, Anita R; Mustian, Karen M; Morrow, Gary R

    2013-04-01

    Nausea and vomiting are two of the most frequent and troubling side effects patients experience during chemotherapy, interfering with compliance with cancer therapies and quality of life. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still major problems for patients receiving chemotherapy. Many cancer patients consider delaying future chemotherapy cycles and some contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the pathopsychophysiology of chemotherapy-induced nausea and vomiting (CINV), the recommended guidelines for treatment, and current agents in late-stage clinical trials, and future research needs to address the continued challenges of treatment-related nausea and vomiting. Despite advances in pharmaceutical and behavioral therapies, and the provision of standard clinical guidelines for effectively managing CINV, patients continue to experience it. Moreover, control of nausea, acute and delayed, and anticipatory nausea and vomiting remains an important, unmet need among cancer patients. It is critical to focus attention on better understanding the mechanisms underlying nausea, anticipatory symptoms and delayed symptoms.

  15. Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management.

    PubMed

    Saxena, Roopali; Rida, Padmashree C G; Kucuk, Omer; Aneja, Ritu

    2016-06-01

    Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono-targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them in clinical translation of such inventions. We are optimistic that clinical implementation of such combination regimens would be a much sought after modality in cancer management.

  16. C-C1-02: Validity of HMO Administrative Data for Breast Cancer Chemotherapy Exposure

    PubMed Central

    Delate, Thomas; Bowles, Erin; Pardee, Roy; Wellman, Robert; Habel, Laurel; Yood, Marianne; Nekhlyudov, Larissa; Goddard, Katrina; Davis, Robert; Mccarty, Catherine; Onitilo, Adedayo; Feigelson, Heather; Freml, Jared; Wagner, Edward

    2011-01-01

    Background/Aims Chemotherapy-related toxicity, while a major focus of randomized clinical trials, has been understudied in population-based research. Eight Cancer Research Network (CRN) sites used Virtual Data Warehouse (VDW) data to examine the risk of cardiotoxicity following chemotherapy for invasive breast cancer. However, information on VDW chemotherapy data validity is limited. This study assessed the validity of VDW data related to the reception and dosages of cardiotoxic chemotherapeutic agents among breast cancer (BC) patients. Methods This was a retrospective, cohort study of women =18 years diagnosed with incident, invasive BC between January 1999 and December 2007. Pharmacy and procedure chemotherapy data were extracted from each site’s administrative databases for up to one year following cancer diagnosis date. Random samples of 50 patients stratified on trastuzumab, anthracyclines, and no chemotherapy exposure were selected from each CRN site for detailed medical chart abstraction. We calculated weighted sensitivities and specificities (and 95% confidence intervals [CI]) of using administrative data to accurately capture chemotherapy treatment compared to medical records. Median cumulative doses calculated from administrative data were compared to median doses obtained from the medical chart using the Spearman’s correlation coefficient. Results The total cohort included 13,497 BC patients. Patients in the random sample (n=400) had a mean age of 65 (±14) years and were primarily white with most tumors diagnosed at AJCC stage 1 or 2. From the sample, 20% (80/400), 38% (152/400), and 40% (158/400) of patients had VDW exposure to trastuzumab, an anthracycline, and any type chemotherapy, respectively. Trastuzumab, anthracycline, and any chemotherapy sensitivities were 97% (CI=94%–98%), 97% (CI=93%–98%), and 99% (CI=97%–99%), respectively; and specificities were 99% (CI=98%–100%), 99% (CI=96%–99%), and 86% (CI=79%–91%), respectively. Median

  17. [High-dose chemotherapy as a strategy to overcome drug resistance in solid tumors].

    PubMed

    Selle, Frédéric; Gligorov, Joseph; Soares, Daniele G; Lotz, Jean-Pierre

    2016-10-01

    The concept of high-doses chemotherapy was developed in the 1980s based on in vitro scientific observations. Exposure of tumor cells to increasing concentrations of alkylating agents resulted in increased cell death in a strong dose-response manner. Moreover, the acquired resistance of tumor cells could be overcome by dose intensification. In clinic, dose intensification of alkylating agents resulted in increased therapeutic responses, however associated with significant hematological toxicity. Following the development of autologous stem cells transplantation harvesting from peripheral blood, the high-doses of chemotherapy, initially associated with marked toxic effects, could be more easily tolerated. As a result, the approach was evaluated in different types of solid tumors, including breast, ovarian and germ cell tumors, small cell lung carcinoma, soft tissue sarcomas and Ewing sarcoma. To date, high-doses chemotherapy with hematopoietic stem cells support is only used as a salvage therapy to treat poor prognosis germ cell tumors patients with chemo-sensitive disease. Regarding breast and ovarian cancer, high-doses chemotherapy should be considered only in the context of clinical trials. However, intensive therapy as an approach to overcome resistance to standard treatments is still relevant. Numerous efforts are still ongoing to identify novel therapeutic combinations and active treatments to improve patients' responses.

  18. A Novel and Selective Poly (ADP-Ribose) Polymerase Inhibitor Ameliorates Chemotherapy-Induced Painful Neuropathy

    PubMed Central

    Ta, Lauren E.; Schmelzer, James D.; Bieber, Allan J.; Loprinzi, Charles L.; Sieck, Gary C.; Brederson, Jill D.; Low, Philip A.; Windebank, Anthony J.

    2013-01-01

    Background Chemotherapy-induced neuropathy is the principle dose limiting factor requiring discontinuation of many chemotherapeutic agents, including cisplatin and oxaliplatin. About 30 to 40% of patients receiving chemotherapy develop pain and sensory changes. Given that poly (ADP-ribose) polymerase (PARP) inhibition has been shown to provide neuroprotection, the current study was developed to test whether the novel PARP inhibitor compound 4a (analog of ABT-888) would attenuate pain in cisplatin and oxaliplatin-induced neuropathy in mice. Results An established chemotherapy-induced painful neuropathy model of two weekly cycles of 10 intraperitoneal (i.p.) injections separated by 5 days rest was used to examine the therapeutic potential of the PARP inhibitor compound 4a. Behavioral testing using von Frey, paw radiant heat, cold plate, and exploratory behaviors were taken at baseline, and followed by testing at 3, 6, and 8 weeks from the beginning of drug treatment. Conclusion Cisplatin-treated mice developed heat hyperalgesia and mechanical allodynia while oxaliplatin-treated mice exhibited cold hyperalgesia and mechanical allodynia. Co-administration of 50 mg/kg or 25 mg/kg compound 4a with platinum regimen, attenuated cisplatin-induced heat hyperalgesia and mechanical allodynia in a dose dependent manner. Similarly, co-administration of 50 mg/kg compound 4a attenuated oxaliplatin-induced cold hyperalgesia and mechanical allodynia. These data indicate that administration of a novel PARP inhibitor may have important applications as a therapeutic agent for human chemotherapy-induced painful neuropathy. PMID:23326593

  19. Paclitaxel-associated reticulate hyperpigmentation: Report and review of chemotherapy-induced reticulate hyperpigmentation

    PubMed Central

    Cohen, Philip R

    2016-01-01

    Drug-induced reticulate hyperpigmentation is uncommon. Including the patient described in this report, chemotherapy-associated reticulate hyperpigmentation has only been described in ten individuals. This paper describes the features of a woman with recurrent and metastatic breast cancer who developed paclitaxel-induced reticulate hyperpigmentation and reviews the characteristics of other oncology patients who developed reticulate hyperpigmentation from their antineoplastic treatment. A 55-year-old Taiwanese woman who developed reticulate hyperpigmentation on her abdomen, back and extremities after receiving her initial treatment for metastatic breast cancer with paclitaxel is described. The hyperpigmentation became darker with each subsequent administration of paclitaxel. The drug was discontinued after five courses and the pigment faded within two months. PubMed was searched with the key words: Breast, cancer, chemotherapy, hyperpigmentation, neoplasm, reticulate, tumor, paclitaxel, taxol. The papers generated by the search, and their references, were reviewed. Chemotherapy-induced reticulate hyperpigmentation has been described in four men and six women. Bleomycin, cytoxan, 5-fluorouracil, idarubacin, and paclitaxel caused the hyperpigmentation. The hyperpigmentation faded in 83% of the patients between two to six months after the associated antineoplastic agent was discontinued. In conclusion, chemotherapy-induced reticulate hyperpigmentation is a rare reaction that may occur during treatment with various antineoplastic agents. The hyperpigmentation fades in most individuals once the treatment is discontinued. Therefore, cancer treatment with the associated drug can be continued in patients who experience this cutaneous adverse event. PMID:28035312

  20. Paclitaxel-associated reticulate hyperpigmentation: Report and review of chemotherapy-induced reticulate hyperpigmentation.

    PubMed

    Cohen, Philip R

    2016-12-16

    Drug-induced reticulate hyperpigmentation is uncommon. Including the patient described in this report, chemotherapy-associated reticulate hyperpigmentation has only been described in ten individuals. This paper describes the features of a woman with recurrent and metastatic breast cancer who developed paclitaxel-induced reticulate hyperpigmentation and reviews the characteristics of other oncology patients who developed reticulate hyperpigmentation from their antineoplastic treatment. A 55-year-old Taiwanese woman who developed reticulate hyperpigmentation on her abdomen, back and extremities after receiving her initial treatment for metastatic breast cancer with paclitaxel is described. The hyperpigmentation became darker with each subsequent administration of paclitaxel. The drug was discontinued after five courses and the pigment faded within two months. PubMed was searched with the key words: Breast, cancer, chemotherapy, hyperpigmentation, neoplasm, reticulate, tumor, paclitaxel, taxol. The papers generated by the search, and their references, were reviewed. Chemotherapy-induced reticulate hyperpigmentation has been described in four men and six women. Bleomycin, cytoxan, 5-fluorouracil, idarubacin, and paclitaxel caused the hyperpigmentation. The hyperpigmentation faded in 83% of the patients between two to six months after the associated antineoplastic agent was discontinued. In conclusion, chemotherapy-induced reticulate hyperpigmentation is a rare reaction that may occur during treatment with various antineoplastic agents. The hyperpigmentation fades in most individuals once the treatment is discontinued. Therefore, cancer treatment with the associated drug can be continued in patients who experience this cutaneous adverse event.

  1. 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.

  2. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial.

    PubMed

    Pujade-Lauraine, Eric; Hilpert, Felix; Weber, Béatrice; Reuss, Alexander; Poveda, Andres; Kristensen, Gunnar; Sorio, Roberto; Vergote, Ignace; Witteveen, Petronella; Bamias, Aristotelis; Pereira, Deolinda; Wimberger, Pauline; Oaknin, Ana; Mirza, Mansoor Raza; Follana, Philippe; Bollag, David; Ray-Coquard, Isabelle

    2014-05-01

    In platinum-resistant ovarian cancer (OC), single-agent chemotherapy is standard. Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC. Eligible patients had measurable/assessable OC that had progressed < 6 months after completing platinum-based therapy. Patients with refractory disease, history of bowel obstruction, or > two prior anticancer regimens were ineligible. After investigators selected chemotherapy (pegylated liposomal doxorubicin, weekly paclitaxel, or topotecan), patients were randomly assigned to single-agent chemotherapy alone or with bevacizumab (10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks) until progression, unacceptable toxicity, or consent withdrawal. Crossover to single-agent bevacizumab was permitted after progression with chemotherapy alone. The primary end point was progression-free survival (PFS) by RECIST. Secondary end points included objective response rate (ORR), overall survival (OS), safety, and patient-reported outcomes. The PFS hazard ratio (HR) after PFS events in 301 of 361 patients was 0.48 (95% CI, 0.38 to 0.60; unstratified log-rank P < .001). Median PFS was 3.4 months with chemotherapy alone versus 6.7 months with bevacizumab-containing therapy. RECIST ORR was 11.8% versus 27.3%, respectively (P = .001). The OS HR was 0.85 (95% CI, 0.66 to 1.08; P < .174; median OS, 13.3 v 16.6 months, respectively). Grade ≥ 2 hypertension and proteinuria were more common with bevacizumab. GI perforation occurred in 2.2% of bevacizumab-treated patients. Adding bevacizumab to chemotherapy statistically significantly improved PFS and ORR; the OS trend was not significant. No new safety signals were observed.

  3. Timing isn't everything: an analysis of when to start salvage chemotherapy in ovarian cancer.

    PubMed

    McMeekin, D Scott; Tillmanns, Todd; Chaudry, Taimur; Gold, Michael; Johnson, Gary; Walker, Joan; Mannel, Robert

    2004-10-01

    Results from GOG 178 showed a prolongation of progression-free survival (PFS) with the immediate use of chemotherapy (CT) following a complete clinical response (CR) in patients with stage III-IV ovarian cancer. We wanted to evaluate our strategy of reserving second line (2nd line) chemotherapy to the time of clinical recurrence by determining PFS intervals following first, second, and third line agents and to compare these finding to results of GOG 178. We conducted a retrospective parallel study to GOG 178 using identical criteria for PFS definitions. Patients (pts) with stage III-IV cancer achieving a CR following surgery and five to eight cycles of platinum-based CT were identified. Patients not obtaining a CR and those with a CR who underwent second look surgery were excluded. Rather than immediately beginning consolidation CT after CR, second line agents were started at recurrence and were followed by a third line when pts progressed. Clinical-pathologic characteristics were abstracted, and time intervals including time to recurrence, time to use of second line CT, time to use of third line (3rd line) CT, and survival were recorded. Time intervals were studied by Kaplan-Meier method. Of 217 reviewed pts (1991-2001), 59 eligible pts were identified. Forty-nine patients had stage III disease and ten had stage IV. At completion of surgery, 44 were optimally debulked. With a median follow-up of 51 months, the median PFS (from CR) of all patients was 20 months. At 5 years, 36% of pts remain disease-free, and 66% of pts are alive. Twenty-three pts have not received second line agents, and thirty-six have received them. For all pts, the median time from CR to start of second line chemotherapy was 21 months, and the median time to start of third line agents was 43 months. Recurrences occurred after 6 months from completion of first line (1st line) therapy in 87% of cases and after 12 months in 50%. Nearly 70% of pts achieving a CR after primary therapy eventually

  4. Natural products for cancer chemotherapy

    PubMed Central

    Demain, Arnold L.; Vaishnav, Preeti

    2011-01-01

    Summary For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti‐tumour activity. A number of these products were first discovered as antibiotics. Another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment. The search for novel drugs is still a priority goal for cancer therapy, due to the rapid development of resistance to chemotherapeutic drugs. In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side‐effects increase the demand for novel anti‐tumour drugs active against untreatable tumours, with fewer side‐effects and/or with greater therapeutic efficiency. This review points out those technologies needed to produce the anti‐tumour compounds of the future. PMID:21375717

  5. Breast Cancer Chemotherapy and Your Heart

    MedlinePlus

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  6. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Cancer.gov

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  7. [Value of systemic chemotherapy in bladder cancer].

    PubMed

    Goebell, P J; vom Dorp, F; Rübben, H

    2006-05-01

    Almost half of the patients with muscle invasive disease already harbor at the time of their first diagnosis occult or distant metastases. Systemic disease has a poor prognosis with a long term survival of less than 10%. The administration of systemic chemotherapy aims to improve the course of locally advanced or metastatic disease.A survival benefit of 5% for patients receiving neoadjuvant and 9-11% using adjuvant chemotherapy is in the first scenario minimal, in the adjuvant setting to be noteworthy. The MVAC-schedule and the Gemcitabine/Cisplatin-combination chemotherapy have to be regarded as standard for induction chemotherapy. However, the 5-year survival rates with 15 or 13% are disappointing.Thus, prognostic factors gain importance since with their consideration significant differences in survival rates can be found. Hope is provided by a novel class of substances, the target-specific drugs, which selectively interfere with the cascade of steps involved in tumorigenesis.

  8. Effects of radiation therapy and chemotherapy on testicular function

    SciTech Connect

    Kinsella, T.J. )

    1989-01-01

    Chemotherapy and radiation therapy are commonly used alone or in combination in the curative management of many malignancies in adolescent and adult males. Over the last 15-20 years, the striking success in the treatment of some common cancers in reproductive males has led to increasing concern for damage to normal tissues, such as the testes, resulting from curative cancer treatment. Indeed, a major future goal for cancer treatment will be to improve on the complication-free cure rate. Inherent in achieving this goal is to understand the pathophysiology and clinical expression of testicular injury. Both chemotherapy and radiation therapy result in germ cell depletion with the development of oligo- to azoospermia and testicular atrophy. The type of drug (particularly the alkylating agents), duration of treatment, intensity of treatment, and drug combination are major variables in determining the extent and duration of testicular injury. Testicular injury with chemotherapy also appears to vary with the age of the patient at the time of treatment. Newer drug combinations are now being used which appear to have curative potential in tumors such as Hodgkin's disease and germ cell testicular cancer with less potential for testicular injury. The most accurate and complete information on radiation injury to the testes is derived from two studies of normal volunteers who received graded single doses directly to the testes. A clear dose-response relationship of clinical and histological testicular damage was found with gradual recovery occurring following doses of up to 600 cGy. While these two studies provide an important clinical data base, radiation therapy used in treating cancers involves multiple daily treatments, usually 25-35 delivered over several weeks. Additionally, direct testicular irradiation is seldom used clinically. 37 references.

  9. Thrombotic microangiopathies and antineoplastic agents.

    PubMed

    Grangé, Steven; Coppo, Paul

    2017-04-01

    Thrombotic microangiopathy is a well-described complication of cancer treatment. Its incidence has increased these last decades, as a result of a better awareness of this complication in cancer patients in one hand, but also of a larger array of therapeutic compounds including anti-vascular endothelium growth factor (VEGF) drugs. It is therefore mandatory to recognize these conditions since they have a significant impact in thrombotic microangiopathies management and prognosis. Practitioners should be aware of the more classical antineoplastic agents associated with thrombotic microangiopathies, the mechanisms by which they induce them, and the resulting management and prognosis. Since malignancy itself can induce thrombotic microangiopathies, it is also mandatory to know how to distinguish rapidly those caused by antineoplastic agents from those associated with cancer, for an adapted management. Thrombotic microangiopathies associated with chemotherapy remain of dismal prognosis. A better understanding of pathophysiology in these forms of thrombotic microangiopathies, in association with a more empirical approach through the use of new therapeutic agents that can also help in the understanding on new mechanisms a posteriori, should improve their prognosis. The preliminary encouraging results reported with complement blockers in this field could represent a convincing example. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.

  10. Pharmacologic Agents for Chronic Diarrhea.

    PubMed

    Lee, Kwang Jae

    2015-10-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly.

  11. Pharmacologic Agents for Chronic Diarrhea

    PubMed Central

    2015-01-01

    Chronic diarrhea is usually associated with a number of non-infectious causes. When definitive treatment is unavailable, symptomatic drug therapy is indicated. Pharmacologic agents for chronic diarrhea include loperamide, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, diosmectite, cholestyramine, probiotics, antispasmodics, rifaximin, and anti-inflammatory agents. Loperamide, a synthetic opiate agonist, decreases peristaltic activity and inhibits secretion, resulting in the reduction of fluid and electrolyte loss and an increase in stool consistency. Cholestyramine is a bile acid sequestrant that is generally considered as the first-line treatment for bile acid diarrhea. 5-HT3 receptor antagonists have significant benefits in patients with irritable bowel syndrome (IBS) with diarrhea. Ramosetron improves stool consistency as well as global IBS symptoms. Probiotics may have a role in the prevention of antibiotic-associated diarrhea. However, data on the role of probiotics in the treatment of chronic diarrhea are lacking. Diosmectite, an absorbent, can be used for the treatment of chronic functional diarrhea, radiation-induced diarrhea, and chemotherapy-induced diarrhea. Antispasmodics including alverine citrate, mebeverine, otilonium bromide, and pinaverium bromide are used for relieving diarrheal symptoms and abdominal pain. Rifaximin can be effective for chronic diarrhea associated with IBS and small intestinal bacterial overgrowth. Budesonide is effective in both lymphocytic colitis and collagenous colitis. The efficacy of mesalazine in microscopic colitis is weak or remains uncertain. Considering their mechanisms of action, these agents should be prescribed properly. PMID:26576135

  12. Olanzapine: An Antiemetic Option for Chemotherapy-Induced Nausea and Vomiting

    PubMed Central

    Brafford, Megan V.; Glode, Ashley

    2014-01-01

    Despite the appropriate use of pharmacologic and nonpharmacologic preventative measures, chemotherapy-induced nausea and vomiting (CINV) can be debilitating and can decrease quality of life for many patients. In addition, patients may be unwilling to continue chemotherapy treatment due to the uncontrollable nausea and vomiting associated with their therapy. Refractory CINV can occur at any point in a treatment cycle, despite adequate therapy for acute and delayed CINV. Current prevention strategies include using serotonin (5-HT3) receptor antagonists, corticosteroids, and/or neurokinin-1 receptor antagonists. Unfortunately, more pharmacologic options are needed to treat refractory CINV. The current standard of care for the treatment of refractory CINV includes phenothiazines, metoclopramide, butyrophenones, corticosteroids, cannabinoids, anticholinergics, and 5-HT3 receptor antagonists. Olanzapine, an atypical antipsychotic agent of the thiobenzodiazepine class, has the ability to target many different receptors, making it an attractive antiemetic agent. PMID:25032030