Incidence, risk factors and treatment outcomes of extravasation of cytotoxic agents in an outpatient chemotherapy clinic.

PubMed

Sakaida, Emiko; Sekine, Ikuo; Iwasawa, Shunichiro; Kurimoto, Ryota; Uehara, Takashi; Ooka, Yoshihiko; Akanuma, Naoki; Tada, Yuji; Imai, Chiaki; Oku, Tomoko; Takiguchi, Yuichi

2014-02-01

Extravasation, the accidental leakage of an anticancer agent from a vessel into the surrounding tissues, can lead to irreversible local injuries and severe disability. Despite its considerable clinical importance, evidence-based information on extravasation in chemotherapy is lacking. This study characterized the clinical features of extravasation and identified issues to be resolved in current cancer chemotherapy performed in outpatient settings. We retrospectively reviewed the medical charts of patients who received chemotherapy and sustained extravasation in our Outpatient Chemotherapy Clinic from April 2007 to August 2012. Chemotherapy administration and extravasation management procedures were standardized using the in-house chemotherapy guideline. Among 43 557 patients who received chemotherapy, 35 (0.08%) experienced extravasation. The duration between the start of infusion and extravasation was >2 h in 28 (80.0%) patients. The severity of extravasation was Grades 1, 2 and 3 in 28, 2 and 5 patients, respectively-three of whom were associated with port trouble. The contributing factor for extravasation was walking in 11 (31.4%) patients. All extravasations were cured without surgical intervention by management according to our guidelines. The incidence of extravasation is as low as 0.08%, using our in-house chemotherapy guideline. Extravasation from implanted ports tends to be severe.

Conventional chemotherapy or hypomethylating agents for older patients with acute myeloid leukaemia?

PubMed

Ferrara, Felicetto

2014-03-01

Acute myeloid leukaemia (AML) is the second more frequent hematologic malignancy in developed countries and primarily affects older adults with a median age at diagnosis of 69 years. Given the progressive ageing of the general population, the incidence of the disease in elderly people is expected to further increase in the years to come. Along with cytogenetics at diagnosis, age represents the most relevant prognostic factor in AML, in that the outcome steadily declines with increasing age. Reasons for poor prognosis include more frequent unfavourable karyotype and other adverse biologic characteristics, such as high rates of expression of genes drug resistance related and high prevalence of secondary AML. Noticeably, as compared with young adults, poorer results in elderly patients have been reported within any cytogenetic and molecular prognostic subgroup, because of frequent comorbid diseases, which render many patients ineligible to intensive chemotherapy. Therefore, predictive models have been developed with the aim of achieving best therapeutic results avoiding unnecessary toxicity. Following conventional induction therapy, older AML patients have complete remission rates in the range of 45-65%, and fewer than 10% of them survive for a minimum of 5 years. On the other hand, hypomethylating agents, such as azacytidine and decitabine offer the possibility of long-term disease control without necessarily achieving complete remission and can represent a reasonable alternative to intensive chemotherapy. Either intensive chemotherapy or hypomethylating agents have lights and shadows, and the therapeutic selection is often influenced by physician's and patient's attitude rather than definite criteria. Research is progress in order to assess predictive biologic factors, which would help clinicians in the selection of patients who can take actual benefit from different therapeutic options. Copyright © 2013 John Wiley & Sons, Ltd.

Medical treatment of advanced non-small cell lung cancer in elderly patients: a review of the role of chemotherapy and targeted agents.

PubMed

Meoni, Giulia; Cecere, Fabiana Letizia; Lucherini, Elisa; Di Costanzo, Francesco

2013-07-01

Lung cancer is the leading cause of cancer related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of all cases. Half of the patients at diagnosis of NSCLC are over seventy years old; therefore, the elderly represent a large subgroup of patients affected by advanced NSCLC in our clinical practice. Nevertheless, the elderly are under-represented in clinical trials. Given the fact that old age is frequently associated with several comorbidities, poor general conditions and physiologic reduction in organ function, clinicians must carefully choose the best treatment option for elderly patients with advanced NSCLC, always taking into account the expected risks and benefits. In this paper we perform a review of literature evidence regarding the medical treatment of elderly patients affected by advanced NSCLC, encompassing single-agent chemotherapy, doublet chemotherapy and targeted agents. We conclude that single-agent chemotherapy with a third generation agent (vinorelbine, taxanes, gemcitabine) represents a valid treatment option for elderly patients who are not eligible for a combination chemotherapy due to clinical features such as comorbidities, poor performance status and inadequate organ function. Platinum-based doublet chemotherapy shows similar efficacy in elderly patients as compared to their younger counterpart, despite greater treatment related toxicity and it is indicated in elderly patients with ECOG PS: 0-2, adequate organ function and no major comorbidities. Elderly patients affected by epidermal growth factor receptor (EGFR) mutated NSCLC benefit mostly from a tyrosine kinase inhibitor of EGFR (erlotinib, gefitinib) which is associated with a good toxicity profile. Currently there are no available data to strongly support the use of bevacizumab in combination with first line chemotherapy in the treatment of older adults. Elderly patients affected by NSCLC harboring the EML4-ALK translocation could benefit mostly from a treatment

Discovery of antitubulin agents with antiangiogenic activity as single entities with multitarget chemotherapy potential.

PubMed

Gangjee, Aleem; Pavana, Roheeth Kumar; Ihnat, Michael A; Thorpe, Jessica E; Disch, Bryan C; Bastian, Anja; Bailey-Downs, Lora C; Hamel, Ernest; Bai, Rouli

2014-05-08

Antiangiogenic agents (AA) are cytostatic, and their utility in cancer chemotherapy lies in their combination with cytotoxic chemotherapeutic agents. Clinical combinations of vascular endothelial growth factor receptor-2 (VEGFR2) inhibitors with antitubulin agents have been particularly successful. We have discovered a novel, potentially important analogue, that combines potent VEGFR2 inhibitory activity (comparable to that of sunitinib) with potent antitubulin activity (comparable to that of combretastatin A-4 (CA)) in a single molecule, with GI50 values of 10(-7) M across the entire NCI 60 tumor cell panel. It potently inhibited tubulin assembly and circumvented the most clinically relevant tumor resistance mechanisms (P-glycoprotein and β-III tubulin expression) to antimicrotubule agents. The compound is freely water-soluble as its HCl salt and afforded excellent antitumor activity in vivo, superior to docetaxel, sunitinib, or Temozolomide, without any toxicity.

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.

A prospective randomized phase II study comparing metronomic chemotherapy with chemotherapy (single agent cisplatin), in patients with metastatic, relapsed or inoperable squamous cell carcinoma of head and neck.

PubMed

Patil, Vijay Maruti; Noronha, Vanita; Joshi, Amit; Muddu, Vamshi Krishna; Dhumal, Sachin; Bhosale, Bharatsingh; Arya, Supreeta; Juvekar, Shashikant; Banavali, Shripad; D'Cruz, Anil; Bhattacharjee, Atanu; Prabhash, Kumar

2015-03-01

Cetuximab based treatment is the recommended chemotherapy for head and neck squamous cell cancers in the palliative setting. However, due to financial constraints, intravenous (IV) chemotherapy without cetuximab is commonly used in lesser developed countries. We believe that oral metronomic chemotherapy may be safer and more effective in this setting. We conducted an open label, superiority, parallel design, randomized phase II trial comparing oral MCT [daily celecoxib (200mg twice daily) and weekly methotrexate (15mg/m(2))] to intravenous single agent cisplatin (IP) (75mg/m(2)) given 3 weekly. Eligible patients had head and neck cancers requiring palliative chemotherapy with ECOG PS 0-2 and adequate organ functions who could not afford cetuximab. The primary end point was progression-free survival. 110 Patients were recruited between July 2011 to May 2013, 57 randomized to the MCT arm and 53 to the IP arm. Patients in the MCT arm had significantly longer PFS (median 101 days, 95% CI: 58.2-143.7 days) compared to the IP arm (median 66 days, 95% CI; 55.8-76.1 days) (p=0.014). The overall survival (OS) was also increased significantly in the MCT arm (median 249 days, 95% CI: 222.5-275.5 days) compared to the IP arm (median 152 days, 95% CI: 104.2-199.8 days) (p=0.02). There were fewer grade 3/4 adverse effects with MCT, which was not significant. (18.9% vs. 31.4%, P=0.14). Oral metronomic chemotherapy has significantly better PFS and OS than single agent platinum in the palliative setting. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Metronomic chemotherapy and nanocarrier platforms.

PubMed

Abu Lila, Amr S; Ishida, Tatsuhiro

2017-08-01

The therapeutic concept of administering chemotherapeutic agents continuously at lower doses, relative to the maximum tolerated dose (MTD) without drug-free breaks over extended periods -known as "metronomic chemotherapy"- is a promising approach for anti-angiogenic cancer therapy. In comparison with MTD chemotherapy regimens, metronomic chemotherapy has demonstrated reduced toxicity. However, as a monotherapy, metronomic chemotherapy has failed to provide convincing results in clinical trials. Therapeutic approaches including combining the anti-angiogenic "metronomic" therapy with conventional radio-/chemo-therapy and/or targeted delivery of chemotherapeutic agents to tumor tissues via their encapsulation with nanocarrier-based platforms have proven to potentiate the overall therapeutic outcomes. In this review, therefore, we focused on the mutual contribution made by nanoscale drug delivery platforms to the therapeutic efficacy of metronomic-based chemotherapy. In addition, the influence that the dosing schedule has on the overall therapeutic efficacy of metronomic chemotherapy is discussed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lacher, M.J.; Toner, K.

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 changemore » 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.« less

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.

[An Elderly Patient with Metastatic Colon Cancer Achieved Long-Term Survival Following Single-Agent Chemotherapy with S-1].

PubMed

Muto, Yuta; Chochi, Kentaro; Morita, Daisaku; Oka, Atsuo; Rikiyama, Toshiki

2018-01-01

Colorectal cancer is a common malignancy and a major health issue in geriatrics. Systemic chemotherapy should be considered for elderly patients. We report an 85-year-old man with metastatic cecal cancer who has achieved long-term survival following single-agent chemotherapy with S-1. His fecal occult blood test results were positive; he then underwent colonoscopy and was diagnosed with cecal cancer. Chest CT revealed multiple metastases in both lungs. Since radical excision was infeasible, we performed right hemicolectomy to prevent bowel obstruction. Histological examination revealed a T3, N0, M1a (PUL2), Stage IV tumor. After discharge from the hospital, the patient preferred receiving chemotherapy that would have fewer side effects. S-1 monotherapy was administered. Despite increased progression of the pulmonary metastases, he experienced no subjective symptoms, his QOL remained consistent, and he completed 42 cycles of chemotherapy in total. The patient is currently being managed on an outpatient basis. In conclusion, elderly patients with cancer should be carefully evaluated according to both disease control and individual circumstances, such as patient's tolerability, QOL, and preference.

High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy.

PubMed

Ridola, Vita; Grill, Jacques; Doz, Francois; Gentet, Jean-Claude; Frappaz, Didier; Raquin, Marie-Anne; Habrand, Jean-Louis; Sainte-Rose, Christian; Valteau-Couanet, Dominique; Kalifa, Chantal

2007-07-01

The objective of the current study was to determine the outcome of children with local recurrence or progression of medulloblastoma in patients who received high-dose chemotherapy (HDC) and posterior fossa (PF) irradiation. HDC consisted in busulfan at a dose of 600 mg/m(2) and thiotepa at a dose of 900 mg/m(2) followed by autologous stem cells transplantation (ASCT). PF radiotherapy was delivered at doses from 50 grays (Gy) to 55 Gy on Day +70 after ASCT. Twenty-seven patients developed local recurrence of an initially completely resected medulloblastoma. Twelve patients had local residual disease after surgery and were enrolled into the salvage protocol at the time of local disease progression under conventional chemotherapy. Acute toxicity consisted mainly in hepatic veno-occlusive disease (33% of patients) and bone marrow aplasia. Two toxic deaths (5%) from infections were reported. The 5-year overall survival rate after this salvage treatment (OS(5y)) for the 39 children who were treated was 68.8% (95% confidence interval [95% CI], 53-81.2%). In the group of patients who were treated for local recurrence, the OS(5y) was 77.2% (95% CI, 58.3-89.1%). Patients with local residual disease who were treated at the time of disease progression had an OS(5y) after salvage treatment of only 50% (95% CI, 25.4-74.6%; P = .09). The treatment strategy that was used in this study had manageable immediate toxicity and resulted in a high overall survival rate in the setting of young children with medulloblastoma who developed local recurrence or disease progression. Copyright (c) 2007 American Cancer Society.

Female cancer survivors exposed to alkylating-agent chemotherapy have unique reproductive hormone profiles.

PubMed

Johnson, Lauren; Sammel, Mary D; Schanne, Allison; Lechtenberg, Lara; Prewitt, Maureen; Gracia, Clarisa

2016-12-01

To evaluate reproductive hormone patterns in women exposed to alkylating-agent chemotherapy. Prospective cohort. University hospital. Normally menstruating mid-reproductive-age women (20-35 years old) who had previously been exposed to alkylating-agent chemotherapy for cancer treatment were compared with two healthy control populations: similarly-aged women and late-reproductive-age women (43-50 years old). Subjects collected daily urine samples for one cycle. Integrated urinary pregnanediol glucuronide (PDG) and estrone conjugate (E1c) and urinary excretion of gonadotropins (FSH and LH). Thirty-eight women (13 survivors, 11 same-age control subjects, 14 late-reproductive-age control subjects) provided 1,082 urine samples. Cycle length, luteal phase length, and evidence of luteal activity were similar among the groups. As expected, ovarian reserve was impaired in cancer survivors compared with same-age control subjects but similar between survivors and late-reproductive-age control subjects. In contrast, survivors had total and peak PDG levels that were similar to same-age control subjects and higher than those observed in late-reproductive-age control subjects. Survivors had higher E1c levels than both same-age and late-reproductive-age control subjects. There was no difference in urinary gonadotropins among the groups. Women exposed to alkylating agents have a unique reproductive hormone milieu that is not solely explained by age or ovarian reserve. The urinary hormone profile observed in survivors appears more similar to same-age control subjects than to late-reproductive-age women with similar ovarian reserve, which may suggest that age plays a more important role than ovarian reserve in the follicular dynamics of survivors. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo

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 inmore » 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.« less

Benefits of adjuvant chemotherapy in high-grade gliomas.

PubMed

DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Adenosine triphosphate-based chemotherapy response assay-guided chemotherapy in unresectable colorectal liver metastasis

PubMed Central

Hur, H; Kim, N K; Kim, H G; Min, B S; Lee, K Y; Shin, S J; Cheon, J H; Choi, S H

2012-01-01

Background: This study aims to evaluate the effectiveness of adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided neoadjuvant chemotherapy for increasing resectability in patients with unresectable colorectal liver metastasis. Patients and methods: Patients were randomised into two groups: Group A was treated by conventional chemotherapy regimen and Group B was treated by chemotherapy regimen according to the ATP-CRA. Three chemotherapeutic agents (5-fluorouracil, oxaliplatin and irinotecan) were tested by ATP-CRA and more sensitive agents were selected. Either FOLFOX or FOLFIRI was administered. Between Group A and B, treatment response and resectability were compared. Results: Between November 2008 and October 2010, a total 63 patients were randomised to Group A (N=32) or Group B (N=31). FOLFOX was more preferred in Group A than in Group B (26 out of 32 (81.3%) vs 20 out of 31 (64.5%)). Group B showed better treatment response than Group A (48.4% vs 21.9%, P=0.027). The resectability of hepatic lesion was higher in Group B (35.5% vs 12.5%, P=0.032). Mean duration from chemotherapy onset to the time of liver resection was 11 cycles (range 4–12) in Group A and 8 cycles (range 8–16) in Group B. Conclusion: This study showed that tailored-chemotherapy based on ATP-CRA could improve the treatment response and resectability in initially unresectable colorectal liver metastasis. PMID:22068817

Chemotherapy-induced hypocalcemia.

PubMed

Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

2010-01-01

To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

Extravasation of chemotherapy.

PubMed

Langer, Seppo W

2010-07-01

Extravasation of chemotherapy is a feared complication of anticancer therapy. The accidental leakage of cytostatic agents into the perivascular tissues may have devastating short-term and long-term consequences for patients. In recent years, the increased focus on chemotherapy extravasation has led to the development of international guidelines that have proven useful tools in daily clinical practice. Moreover, the tissue destruction in one of the most dreaded types of extravasation (ie, anthracycline extravasation) now can effectively be prevented with a specific antidote, dexrazoxane.

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.

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.

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.

Induction chemotherapy in acute myeloid leukaemia: origins and emerging directions.

PubMed

Upadhyay, Vivek A; Fathi, Amir T

2018-03-01

This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations. Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody drug conjugates and liposomal formulations have demonstrated significant potential as modifications to traditional induction chemotherapy.

Cytotoxic chemotherapy in the treatment of advanced renal cell carcinoma in the era of targeted therapy.

PubMed

Diamond, E; Molina, A M; Carbonaro, M; Akhtar, N H; Giannakakou, P; Tagawa, S T; Nanus, D M

2015-12-01

Renal cell carcinoma (RCC) is a heterogeneous disease with regards to histology, progression, and response to treatment. Cytotoxic chemotherapy has been extensively studied in metastatic RCC (mRCC). Responses in most studies are modest and the mechanisms of resistance remain poorly understood. Targeted therapies have significantly improved outcomes in mRCC; however, most patients eventually relapse and die of their disease. Early clinical data suggest that combinations of chemotherapy and targeted agents are clinically active and are well tolerated. We reviewed the available literature for published clinical trials incorporating traditional chemotherapeutic agents in the treatment of mRCC. These papers were identified through a Medline search and were included if they employed at least one chemotherapeutic agent in the treatment of mRCC. The literature was also reviewed for information regarding mechanisms of chemotherapy resistance. The data regarding the use of cytotoxic chemotherapy in mRCC consist of small, non-randomized phase I and II studies. The major response proportions with single agent chemotherapies are low but combination regimens either with other cytotoxic agents, cytokines, or targeted agents have demonstrated moderate activity. Disparate trial designs and lack of head to head clinical trials make it difficult to compare the efficacy of chemotherapy with that of immunotherapy or targeted agents. Chemotherapy is particularly useful in patients with collecting duct histology and predominantly sarcomatoid differentiation. Chemotherapy resistance may be mediated by overexpression of p-glycoprotein efflux pumps and the dysregulation of the microtubule-hypoxia inducible factor signaling axis. The role of cytotoxic chemotherapy in the treatment for clear cell RCC remains poorly defined. Cytotoxic chemotherapy is considered a standard of care in patients with mRCC with predominantly sarcomatoid differentiation and collecting duct RCC variants (Motzer et al

[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.

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.

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.

Alternative Therapy and Abnormal Liver Function During Adjuvant Chemotherapy in Breast Cancer Patients

PubMed Central

Ahn, Jin-Hee; Kim, Sung-Bae; Yun, Mi Ra; Lee, Jung-Shin; Kang, Yoon-Koo

2004-01-01

Although hepatotoxicity has been rarely reported during adjuvant chemotherapy in breast cancer patients, we observed a high frequency in our patients who were also taking alternative agents. We therefore sought to determine the association between hepatotoxicity and alternative agents during adjuvant chemotherapy in breast cancer patients. All breast cancer patients were treated with the same chemotherapeutic regimen and had normal baseline liver function test (LFT). LFT was checked repeatedly during each cycle of chemotherapy. Patients showing LFT abnormalities were asked about use of alternative agents, and, after the end of chemotherapy, a questionnaire was administered to each patient on their use of alternative agents. Of 178 patients, 65 (36.5%) admitted using alternative therapy, and significantly more patients in this group developed LFT abnormalities (37/65, 56.9%) than those who denied taking alternative therapy (25/113, 22.1%, p=0.001). Although LFT abnormalities were mild to moderate and normalized in most patients after cessation of alternative agents, it remained a serious problem in one patient. In conclusion, alternative therapy may be one of the etiologies for abnormal LFT in breast cancer patients receiving adjuvant chemotherapy. PMID:15201506

Recent Advances in Chemotherapy and Surgery for Colorectal Liver Metastases.

PubMed

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

2016-11-01

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). (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.

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

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

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.

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.

Adjuvant chemotherapy for osteosarcoma.

PubMed

Eilber, F R; Rosen, G

1989-08-01

From this review of chemotherapy trials, several observations can be made. Osteosarcoma is a complex disease involving multiple histologies, each with a different prognosis. Prognostic factors that have been shown to be important include anatomic location of the primary tumor, stage at presentation (patients with metastatic or local recurrent disease fair far worse than those with primary disease), age at onset (children fair worse than the teenager with osteosarcoma), and location within the extremity (patients with more distal tumors fairing better than patients with more proximal tumors). There is convincing evidence for the efficacy of chemotherapeutic agents such as methotrexate in high doses (at least 8 g/m2 for adults, 12 g/m2 for children), Adriamycin, and cisplatin. The combination of Adriamycin and cisplatin appears to be more beneficial relative to either one of these agents alone. The efficacy of the combination of BCD as a triple-drug regimen, although useful in several different trials, has not been convincingly shown. Finally, from several of the recent randomized trials, it appears, that chemotherapeutic regimens containing an Adriamycin and cisplatin combination appear to be superior to those that do not include this combination. However, these observations are made from a historical perspective and have not been conclusively proven by randomized prospective investigations. The observations concerning the natural history of the disease and the activity of various chemotherapeutic agents suggest certain clinical practice algorithms. Essential staging procedures would include a bone scan looking for multifocal or metastatic disease, and CT scans of the chest looking for metastases to the lung. From all studies, it is apparent that surgery is mandatory for the primary tumor and should be an integral portion of all treatment methods. Chemotherapy should be considered for all patients with osteosarcoma, and the essential drugs in the regimen appear at

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.

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

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.

Intrathecal chemotherapy for refractory disseminated medulloblastoma.

PubMed

Yoshimura, Junichi; Nishiyama, Kenichi; Mori, Hiroshi; Takahashi, Hideaki; Fujii, Yukihiko

2008-05-01

To analyze the effect of intrathecal (IT) chemotherapy for disseminated medulloblastoma. Twenty-one patients received IT chemotherapy using the chemotherapeutic agents of methotrexate (MTX) and nitrosoureas (ACNU, MCNU) including nine patients for residual leptomeningeal lesions after initial surgery and radiation, and 12 for a recurrence with leptomeningeal dissemination. Of these 21 patients, 12 received a lumbar and/or ventricular bolus injection of the chemotherapeutic agents, one received the ventriculolumbar perfusion of the agents, and eight received both the perfusion and bolus injection. The doses ranged from 6-7 mg/m(2) of ACNU for perfusion and 3-3.5 mg/m(2) of ACNU, MCNU, or MTX for the bolus injection, and the cycles were administered from 3 to 12 times for perfusion and from 5 to 54 times for the bolus injection. The effects of chemotherapy were assessed by both radiological and cytological examinations, and the clinical symptoms were also assessed. Radiological and/or cytological responses were observed in 10 of 21 patients (47.6%), including seven cases demonstrating a complete remission. The 5-year overall survival rate and 5-year survival rate after dissemination were 61.5 and 46.4%, respectively. Five patients who received a lumbar bolus injection of nitrosoureas experienced paraplegia and double incontinence. One patient who received a ventricular injection of nitrosoureas experienced truncal ataxia. IT chemotherapy was found to be effective in some cases with refractory disseminated medulloblastoma and it seems to be an appropriate treatment choice for leptomeningeal recurrence. However, the frequent bolus injections of nitrosoureas should be avoided to prevent the side effects.

[Multiple post-chemotherapy plantar nevi].

PubMed

Hueso, Luis; Requena, Celia; Serra-Guillén, Carlos; Alfaro, Alberto; Nagore, Eduardo; Llombart, Beatriz; Botella-Estrada, Rafael; Sanmartín, Onofre; Guillén, Carlos

2006-06-01

The induction of multiple melanocytic nevi in children after chemotherapy has been documented in the literature. This situation apparently has more to do with the state of immunosuppression that is produced than with any specific agent used. We present the case of a 12-year-old girl who presented with multiple plantar melanocytic nevi after multidrug chemotherapy for acute lymphocytic leukemia. None of the lesions showed any alarming clinical signs. Although the degeneration of post-chemotherapy melanocytic nevi to melanoma has not been documented in any of the cases described, the presence of a high number of melanocytic nevi is an accepted risk factor for melanoma; thus, close clinical follow-up of these patients seems advisable.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

Chemotherapy Near the End of Life for Chinese Patients with Solid Malignancies

PubMed Central

Sheng, Jin; Zhang, Ya‐Xiong; He, Xiao‐Bo; Fang, Wen‐Feng; Yang, Yun‐Peng; Lin, Gui‐Nan; Wu, Xuan; Li, Ning; Zhang, Jing; Zhai, Lin‐Zhu; Zhao, Yuan‐Yuan; Huang, Yan; Zhou, Ning‐Ning; Zhao, Hong‐Yun

2016-01-01

Abstract Introduction. There are increasing concerns about the negative impacts of chemotherapy near the end of life (EOL). There is discrepancy among different countries about its use, and little is known about the real‐world situation in China. Patients and Methods. This retrospective study was conducted at six representative hospitals across China. Adult decedents with a record of advanced solid cancer and palliative chemotherapy were consecutively screened from 2010 through 2014. The prevalence of EOL chemotherapy within the last 1 month of life was set as the primary outcome. The correlations among EOL chemotherapy, clinicopathological features, and overall survival (OS) were investigated. Results. A total of 3,350 decedents who had had cancer were consecutively included; 2,098 (62.6%) were male and the median age was 56 years (range, 20–88). There were 177 (5.3%), 387 (11.6%), and 837 (25.0%) patients who received EOL chemotherapy within the last 2 weeks, 1 month, and 2 months of life, respectively. We identified inferior OS (median OS, 7.1 vs. 14.2 months; hazard ratio, 1.37; 95% confidence interval [CI], 1.23–1.53; p < .001), more intensive treatments (e.g., admitted to intensive care unit [ICU] in the last month of life, received cardiopulmonary resuscitation and invasive ventilation support), and hospital death (odds ratio, 1.53; 95% CI, 1.14–2.06; p = .005) among patients who received continued chemotherapy within the last month compared with those who did not. However, subgroup analyses indicated that receiving oral agents correlated with fewer ICU admissions and lower rates of in‐hospital death. Conclusion. This study showed that EOL chemotherapy is commonly used in China. Intravenous chemotherapy at the EOL significantly correlated with poor outcomes and the role of oral anticancer agents warrants further investigation. Implications for Practice. The role of chemotherapy toward the end of life (EOL) in patients with solid cancers is

Chemotherapy Near the End of Life for Chinese Patients with Solid Malignancies.

PubMed

Sheng, Jin; Zhang, Ya-Xiong; He, Xiao-Bo; Fang, Wen-Feng; Yang, Yun-Peng; Lin, Gui-Nan; Wu, Xuan; Li, Ning; Zhang, Jing; Zhai, Lin-Zhu; Zhao, Yuan-Yuan; Huang, Yan; Zhou, Ning-Ning; Zhao, Hong-Yun; Zhang, Li

2017-01-01

There are increasing concerns about the negative impacts of chemotherapy near the end of life (EOL). There is discrepancy among different countries about its use, and little is known about the real-world situation in China. This retrospective study was conducted at six representative hospitals across China. Adult decedents with a record of advanced solid cancer and palliative chemotherapy were consecutively screened from 2010 through 2014. The prevalence of EOL chemotherapy within the last 1 month of life was set as the primary outcome. The correlations among EOL chemotherapy, clinicopathological features, and overall survival (OS) were investigated. A total of 3,350 decedents who had had cancer were consecutively included; 2,098 (62.6%) were male and the median age was 56 years (range, 20-88). There were 177 (5.3%), 387 (11.6%), and 837 (25.0%) patients who received EOL chemotherapy within the last 2 weeks, 1 month, and 2 months of life, respectively. We identified inferior OS (median OS, 7.1 vs. 14.2 months; hazard ratio, 1.37; 95% confidence interval [CI], 1.23-1.53; p < .001), more intensive treatments (e.g., admitted to intensive care unit [ICU] in the last month of life, received cardiopulmonary resuscitation and invasive ventilation support), and hospital death (odds ratio, 1.53; 95% CI, 1.14-2.06; p = .005) among patients who received continued chemotherapy within the last month compared with those who did not. However, subgroup analyses indicated that receiving oral agents correlated with fewer ICU admissions and lower rates of in-hospital death. This study showed that EOL chemotherapy is commonly used in China. Intravenous chemotherapy at the EOL significantly correlated with poor outcomes and the role of oral anticancer agents warrants further investigation. The Oncologist 2017;22:53-60Implications for Practice: The role of chemotherapy toward the end of life (EOL) in patients with solid cancers is debatable. This article is believed to be the first

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer

NASA Astrophysics Data System (ADS)

Hervault, Aziliz; Thanh, Nguyêl; N. Thé, Kim

2014-09-01

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

Magnetic nanoparticle-based therapeutic agents for thermo-chemotherapy treatment of cancer.

PubMed

Hervault, Aziliz; Thanh, Nguyen Th Kim

2014-10-21

Magnetic nanoparticles have been widely investigated for their great potential as mediators of heat for localised hyperthermia therapy. Nanocarriers have also attracted increasing attention due to the possibility of delivering drugs at specific locations, therefore limiting systematic effects. The enhancement of the anti-cancer effect of chemotherapy with application of concurrent hyperthermia was noticed more than thirty years ago. However, combining magnetic nanoparticles with molecules of drugs in the same nanoformulation has only recently emerged as a promising tool for the application of hyperthermia with combined chemotherapy in the treatment of cancer. The main feature of this review is to present the recent advances in the development of multifunctional therapeutic nanosystems incorporating both magnetic nanoparticles and drugs, and their superior efficacy in treating cancer compared to either hyperthermia or chemotherapy as standalone therapies. The principle of magnetic fluid hyperthermia is also presented.

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.

Optimal chemotherapy treatment for women with recurrent ovarian cancer

PubMed Central

Fung-Kee-Fung, M.; Oliver, T.; Elit, L.; Oza, A.; Hirte, H.W.; Bryson, P.

2007-01-01

Question What is the optimal chemotherapy treatment for women with recurrent ovarian cancer who have previously received platinum-based chemotherapy? Perspectives Currently, standard primary therapy for advanced disease involves a combination of maximal cytoreductive surgery and chemotherapy with carboplatin plus paclitaxel or with carboplatin alone. Despite initial high response rates, a large proportion of patients relapse, resulting in a therapeutic challenge. Because these patients are not curable, the goal of therapy becomes improvement in both quality and length of life. The search has therefore been to find active agents for women with recurrent disease following platinum-based chemotherapy. Outcomes Outcomes of interest included any combination of tumour response rate, progression-free survival, overall survival, adverse events, and quality of life. Methodology The medline, embase, and Cochrane Library databases were systematically searched for primary articles and practice guidelines. The resulting evidence informed the development of clinical practice recommendations. The systematic review and recommendations were approved by the Report Approval Panel of the Program in Evidence-Based Care, and by the Gynecology Cancer Disease Site Group (dsg). The practice guideline was externally reviewed by a sample of practitioners from Ontario, Canada. Results Thirteen randomized trials compared various chemotherapy regimens for patients with recurrent ovarian cancer. In five of the thirteen trials in which 100% of patients were considered sensitive to platinum-containing chemotherapy, further platinum-based combination chemotherapy significantly improved response rates (two trials), progression-free survival (four trials), and overall survival (three trials) when compared with single-agent chemotherapy involving carboplatin or paclitaxel. Only two of these randomized trials compared the same chemotherapy regimens: carboplatin alone versus the combination of

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

Chemotherapy remains an essential element of personalized care for persons with lung cancers

PubMed Central

Hellmann, M. D.; Li, B. T.; Chaft, J. E.; Kris, M. G.

2016-01-01

Molecularly targeted and immunotherapies have improved the care of patients with lung cancers. These successes have rallied calls to replace or avoid chemotherapy. Yet, even in this era of precision medicine and exciting advances, cytotoxic chemotherapies remain an essential component of lung cancer treatment. In the setting of locoregional disease, chemotherapy is the only systemic therapy thus far proven to enhance curability when combined with surgery or radiation. In the metastatic setting, chemotherapy can improve the length and quality of life in many patients. Chemotherapy remains the mainstay of care for individuals whose cancers with oncogenic drivers have acquired resistance to targeted agents. Chemotherapy also has the potential to modulate the immune system to enhance the effectiveness of immune checkpoint inhibitors. In this context, chemotherapy should be framed as a critical component of the armamentarium available for optimizing cancer care rather than an unfortunate anachronism. We examine the role of chemotherapy with precision medicine in the current care of patients with lung cancers, as well as opportunities for future integration in combinations with targeted agents, angiogenesis inhibitors, immunotherapies, and antibody drug conjugates. PMID:27456296

Clofarabine-based combination chemotherapy for relapse and refractory childhood acute lymphoblastic leukemia.

PubMed

Arakawa, Yuki; Koh, Katsuyoshi; Aoki, Takahiro; Kubota, Yasuo; Oyama, Ryo; Mori, Makiko; Hayashi, Mayumi; Hanada, Ryoji

2014-11-01

Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required.

Nail toxicity induced by cancer chemotherapy.

PubMed

Gilbar, Peter; Hain, Alice; Peereboom, Veta-Marie

2009-09-01

To provide a comprehensive literature review of chemotherapy-induced nail toxicity, including clinical presentation, implicated drugs and approaches for prevention and management. A search of MEDLINE and EMBASE (1966-2008) databases was conducted using the terms (and variations of the terms) antineoplastic agents, nails, nail toxicity, onycholysis, and paronychia. Bibliographies from selected articles were reviewed for appropriate references. The retrieved literature was reviewed to include all articles relevant to the clinical presentation, diagnosis, incidence, prevention, and treatment of chemotherapy-induced nail toxicity. Nail toxicity is a relatively uncommon adverse effect linked to a number of chemotherapeutic agents. Clinical presentation varies, depending on which nail structure is affected and the severity of the insult. Nail changes may involve all or some nails. Toxicity may be asymptomatic and limited to cosmetic concerns, however, more severe effects, involving pain and discomfort can occur. Taxanes and anthracyclines are the antineoplastic drug groups most commonly implicated. It is suggested that the administration schedule may influence the incidence of nail abnormalities, for example reported cases linked to the weekly administration of paclitaxel.Before instituting chemotherapy, patients should be educated regarding potential nail toxicities and strategies for prevention implemented. Management includes appropriate nail cutting, avoiding potential irritants, topical, or oral antimicrobials, and possibly cessation or dose reduction of the offending agent. Cryotherapy, through the application of frozen gloves or socks, has been beneficial in reducing docetaxel-induced nail toxicity and may be effective for other drugs.

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

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

PubMed

Nikolaidi, Eleftheria; Hatzikou, Magdalini; Geitona, Mary

2013-07-16

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. 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. 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 €8.460.119 when biosimilar ESAs were used

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.

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.

[Chemotherapy-induced diarrhea].

PubMed

Kobayashi, Kunihiko

2003-06-01

Chemotherapy-induced diarrhea is a well-documented side effect of many cancer treatments and is associated with increased morbidity and mortality. Chemotherapy-induced diarrhea negatively impacts patient quality of life and treatment outcome by requiring dose limitations or treatment interruption. The chemotherapeutic agent CPT-11 (irinotecan) has shown promising results as a single agent and in combination chemotherapy for the treatment of colorectal and small cell lung cancer. However, delayed onset diarrhea is considered to be its major dose-limiting toxicity. In some cases, it can be life threatening. To prevent CPT-11-induced delayed diarrhea, oral alkalization (OA) and control of defecation (CD) [Int J Cancer 92: 269-275, 2001] were developed based on fundamental studies [Int J Cancer 83: 491-496, 1999; Cancer Res 62: 179-187, 2002]. Oral administration of antibiotics [Cancer Res 56: 3752-3757, 1996; Clin Cancer Res 7: 1136-1141, 2001] or kampo medicine [Jpn J Cancer Res 86: 978-984, 1995; Jpn J Cancer Res 86: 985-989, 1995] to decrease beta-glucuronidase activity derived from bacteria in the large intestine was also reported to be successful in preventing delayed diarrhea. When CPT-11-induced delayed diarrhea occurs, the conventional treatment is loperamide [J Natl Cancer Inst 86: 446-449, 1994], and the early recognition and treatment of diarrhea with this opioid has reduced, although not entirely eliminated, patient morbidity. Other therapies are needed to treat patients with loperamide-refractory CPT-11 induced diarrhea, and the successful use of the somatostatin analogue octreotide has been reported [Support Care Cancer 9: 258-260, 2001; Ann Oncol 12: 227-229, 2001; Proc Am Soc Clin Oncol 21: 387a, 2002].

76 FR 21368 - Evaluation of the Potential Developmental Effects of Cancer Chemotherapy During Pregnancy: Call...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

... Cancer Chemotherapy During Pregnancy: Call for Information and Nomination of Scientific Experts AGENCY... chemotherapy during pregnancy. CERHR invites the submission of information about ongoing studies or upcoming publications on the pregnancy outcomes and long- term health of offspring exposed to cancer chemotherapy agents...

Real-world cost analysis of chemotherapy for colorectal cancer in Japan: detailed costs of various regimens during the entire course of chemotherapy.

PubMed

Yajima, Shuichi; Shimizu, Hisanori; Sakamaki, Hiroyuki; Ikeda, Shunya; Ikegami, Naoki; Murayama, Jun-Ichiro

2016-01-04

Various chemotherapy regimens for advanced colorectal cancer have been introduced to clinical practice in Japan over the past decade. The cost profiles of these regimens, however, remain unclear in Japan. To explore the detailed costs of different regimens used to treat advanced colorectal cancer during the entire course of chemotherapy in patients treated in a practical setting, we conducted a so-called "real-world" cost analysis. A detailed cost analysis was performed retrospectively. Patients with advanced colorectal cancer who had received chemotherapy in a practical healthcare setting from July 2004 through October 2010 were extracted from the ordering system database of Showa University Hospital. Direct medical costs of chemotherapy regimens were calculated from the hospital billing data of the patients. The analysis was conducted from a payer's perspective. A total of 30 patients with advanced colorectal cancer were identified. Twenty patients received up to second-line treatment, and 8 received up to third-line treatment. The regimens identified from among all courses of treatment in all patients were 13 oxaliplatin-based regimens, 31 irinotecan-based regimens, and 11 regimens including molecular targeted agents. The average (95% confidence interval [95% CI]) monthly cost during the overall period from the beginning of treatment to the end of treatment was 308,363 (258,792 to 357,933) Japanese yen (JPY). According to the type of regimen, the average monthly cost was 418,463 (357,413 to 479,513) JPY for oxaliplatin-based regimens, 215,499 (188,359 to 242,639) JPY for irinotecan-based regimens, and 705,460 (586,733 to 824,187) JPY for regimens including molecular targeted agents. Anticancer drug costs and hospital fees accounted for 50 to 77% and 11 to 25% of the overall costs of chemotherapy, respectively. The costs of irinotecan-based regimens were lower than those of oxaliplatin-based regimens and regimens including molecular targeted agents in Japan

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.

mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy

PubMed Central

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

2014-01-01

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 O6-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. PMID:24367102

Oral chemotherapy medications: the need for a nurse's touch.

PubMed

Winkeljohn, Debra L

2007-12-01

Since 2005, many oral chemotherapy agents have been released. Nurses often are not directly involved with patients who receive oral agents. Difficulties with adherence, safety, patient teaching, and access to oral agents can hinder treatment. Nurses can increase adherence and keep patients safe by developing standardized written prescriptions, encouraging the use of patient diaries, offering dosage calendars, and supplying contact information for an office pharmacist.

The continuing role of chemotherapy for advanced non-small cell lung cancer in the targeted therapy era.

PubMed

Lwin, Zarnie; Riess, Jonathan W; Gandara, David

2013-10-01

There have been remarkable advances in the targeted treatment of advanced non-small cell lung cancer (NSCLC) over the past several years. Survival outcomes are steadily improving as management paradigms shift in the diagnosis and treatment of advanced NSCLC. Customizing treatment based on histology and molecular typing has become a standard of care in this era of targeted therapy. While new chemotherapeutic agents have proven effective, the pivotal role of platinum-based chemotherapy doublets has been confirmed. Maintenance chemotherapy has become an option, but who to employ it in remains unclear in the real-world setting. Efforts to overcome resistance to targeted agents are ongoing utilizing combination regimens of chemotherapy plus targeted agents, but optimizing combination strategies needs further exploration. This review highlights recent developments in novel chemotherapeutics and in chemotherapy strategies over the past two years. Despite advances in molecular medicine, there remains an essential role for chemotherapy in advanced NSCLC, even in the recent targeted therapy era.

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.

Third-Line Chemotherapy for Metastatic Urothelial Cancer: A Retrospective Observational Study

PubMed Central

Di Lorenzo, Giuseppe; Buonerba, Carlo; Bellelli, Teresa; Romano, Concetta; Montanaro, Vittorino; Ferro, Matteo; Benincasa, Alfonso; Ribera, Dario; Lucarelli, Giuseppe; De Cobelli, Ottavio; Sonpavde, Guru; De Placido, Sabino

2015-01-01

Abstract The prognosis of locally advanced (T3/T4 or N1) and metastatic disease urothelial carcinoma is poor. In this retrospective study, we reviewed data about patients receiving third-line chemotherapy for metastatic disease, in view of the lack of data in this setting. We retrospectively analyzed medical records of patients with a pathologic diagnosis of urothelial carcinoma treated with systemic chemotherapy for metastatic disease at 4 participating Institutions between January, 2010, and January, 2015. Cox proportional hazards regression was used to evaluate the association of the chemotherapy agent used versus others with overall survival, adjusted for 5 externally validated prognostic factors in advanced urothelial carcinoma. Of 182 patients that received first-line chemotherapy/adjuvant chemotherapy as defined above, 116 patients (63.73%) received second-line salvage treatment. Fifty-two patients were finally included in this analysis, whereas 9 were excluded due to missing data. Third-line chemotherapy was based on cyclophosphamide, platinum, vinflunine, taxanes, and gemcitabine in 16, 12, 11, 10, and 3 patients, respectively. Median PFS (progression-free survival) and OS (overall survival) of the population were 13 (10–17) and 31 (28–36) weeks. Single-agent cyclophosphamide was associated with a PFS of 18 (13–22) and an OS of 38 (33–41) weeks, whereas platinum-based combinations were associated with a PFS of 5 weeks and an OS of 8 weeks. Multivariate analysis showed improved survival in patients treated with cyclophosphamide (hazard ratio (HR) = 0.42; 95% CI: 0.20–0.89; P = 0.025) and a worse survival in those treated with platinum-based regimens (HR: 4.37; 95% CI = 1.95–9.77; P < 0.01). We observed a significantly longer overall survival in patients receiving single-agent cyclophosphamide, with few grade 3 to 4 toxicities. Further studies should assess the efficacy of metronomic single-agent cyclophosphamide in advanced lines

Palliative chemotherapy and targeted therapies for esophageal and gastroesophageal junction cancer.

PubMed

Janmaat, Vincent T; Steyerberg, Ewout W; van der Gaast, Ate; Mathijssen, Ron Hj; Bruno, Marco J; Peppelenbosch, Maikel P; Kuipers, Ernst J; Spaander, Manon Cw

2017-11-28

Almost half of people with esophageal or gastroesophageal junction cancer have metastatic disease at the time of diagnosis. Chemotherapy and targeted therapies are increasingly used with a palliative intent to control tumor growth, improve quality of life, and prolong survival. To date, and with the exception of ramucirumab, evidence for the efficacy of palliative treatments for esophageal and gastroesophageal cancer is lacking. To assess the effects of cytostatic or targeted therapy for treating esophageal or gastroesophageal junction cancer with palliative intent. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Web of Science, PubMed Publisher, Google Scholar, and trial registries up to 13 May 2015, and we handsearched the reference lists of studies. We did not restrict the search to publications in English. Additional searches were run in September 2017 prior to publication, and they are listed in the 'Studies awaiting assessment' section. We included randomized controlled trials (RCTs) on palliative chemotherapy and/or targeted therapy versus best supportive care or control in people with esophageal or gastroesophageal junction cancer. Two authors independently extracted data. We assessed the quality and risk of bias of eligible studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We calculated pooled estimates of effect using an inverse variance random-effects model for meta-analysis. We identified 41 RCTs with 11,853 participants for inclusion in the review as well as 49 ongoing studies. For the main comparison of adding a cytostatic and/or targeted agent to a control arm, we included 11 studies with 1347 participants. This analysis demonstrated an increase in overall survival in favor of the arm with an additional cytostatic or targeted therapeutic agent with a hazard ratio (HR) of 0.75 (95% confidence interval (CI) 0.68 to 0.84, high-quality evidence). The median increased

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

High-dose Carboplatin/Etoposide/Melphalan increases risk of thrombotic microangiopathy and organ injury after autologous stem cell transplantation in patients with neuroblastoma.

PubMed

Jodele, Sonata; Dandoy, Christopher E; Myers, Kasiani; Wallace, Gregory; Lane, Adam; Teusink-Cross, Ashley; Weiss, Brian; Davies, Stella M

2018-04-19

Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplant that can result in multi-organ failure (MOF). Patients undergoing high-dose chemotherapy with autologous stem cell transplant (aHCT) for neuroblastoma require good organ function to receive post-transplant radiation and immunotherapy. We examined TA-TMA incidence and transplant outcomes in patients with neuroblastoma receiving different transplant preparative regimens. Sixty patients underwent aHCT using high-dose chemotherapy: 41 patients received carboplatin/etoposide/melphalan (CEM), 13 patients busulfan/melphalan (Bu/Mel) and six patients received tandem transplant (cyclophosphamide/thiotepa and CEM). TA-TMA with MOF was diagnosed in 13 patients (21.7%) at a median of 18 days after aHCT. TA-TMA occurred in 12 patients receiving CEM and in 1 after cyclophosphamide/thiotepa. There were no incidences of TA-TMA after Bu/Mel regimen. Six of 13 patients with TA-TMA and MOF received terminal complement blocker eculizumab for therapy. They all recovered organ function and received planned post-transplant therapy. Out of seven patients who did not get eculizumab, two died from TA-TMA complications and four progressed to ESRD. We conclude that the CEM regimen is associated with a high incidence of clinically significant TA-TMA after aHCT and eculizumab can be safe and effective treatment option to remediate TA-TMA associated MOF.

[Chemotherapy in epithelial ovarian cancer].

PubMed

Tazi, Y; Pautier, P; Leary, A; Lhomme, C

2013-10-01

Chemotherapy is fundamental in the management of epithelial ovarian carcinomas both for early and advanced stages (rarely surgical treatment alone) and in almost every step of the disease. The reference schema combines carboplatin and paclitaxel intravenously. Intraperitoneal chemotherapy also proved its efficacy after complete surgery for advanced disease and should be reserved to trained teams due to its technical constraints and toxicity issues. Modalities of treatment in relapsed and progressive disease depend mainly on the free interval between this diagnosis and the last dose of platinum. Bevacizumab has proven its effectiveness in prolonging progression-free survival in 1st line setting in association with chemotherapy followed by maintenance and in case of relapse or progression both fore platinum sensitive or resistant disease. Finally, a better understanding of ovarian cancer biology will allow us to consider new molecular-targeted agents guided by the specific characteristics of each patient and each tumor. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Use of metronomic chemotherapy in oncology: results from a national Italian survey.

PubMed

Collovà, Elena; Sebastiani, Federica; De Matteis, Elisabetta; Generali, Daniele; Aurilio, Gaetano; Boccardo, Francesco; Crispino, Sergio; Cruciani, Giorgio

2011-01-01

Metronomic chemotherapy refers to the administration of low doses of cytotoxic agents over a prolonged period of time with no or only short drug-free intervals. It is designed to overcome acquired tumor resistance to chemotherapy and reduce neo-angiogenesis despite a lower toxicity than with standard chemotherapy. The role of metronomic chemotherapy remains controversial, and its optimal therapeutic use has not yet been defined. The present survey was designed as a short questionnaire and was sent to the medical oncologists registered with Medikey, a national database listing all the Italian oncology specialists linked with the Italian Council of Medical Oncology Hospital Consultants (Collegio Italiano Primari Oncologi Medici Ospedalieri, CIPOMO) and the Italian Association of Medical Oncology (Associazione Italiana di Oncologia Medica, AIOM). The questionnaire was completed on a voluntary basis and it was totally anonymous. The questionnaire was sent to 3,289 oncologists, and 191 (5.8%) actively participated in the survey. Seventy-two percent of responders declared that they had administered a regimen of metronomic chemotherapy at least once. Metronomic chemotherapy is commonly used in advanced breast cancer patients, and in most cases it was prescribed after failure of at least two lines of treatment. Oral agents such as cyclophosphamide, capecitabine, methotrexate and vinorelbine were the most commonly prescribed drugs. Nearly 60% of responders was believed to have significantly less toxicity with metronomic chemotherapy than with standard chemotherapy. The sample of oncologists who participated in the survey is small but it appears to be representative of the Italian medical oncology community. The answers to the questionnaire indicate a significant interest in metronomic chemotherapy, which is apparently widely prescribed. This is the first large national survey on the use of metronomic chemotherapy. Considering the results, larger research on metronomic

Chemotherapy induced toxicity is highly heritable in Drosophila melanogaster

PubMed Central

Kislukhin, Galina; Murphy, Maura L.; Jafari, Mahtab; Long, Anthony D.

2012-01-01

Objectives Identifying the genes responsible for chemotherapy toxicity in Drosophila melanogaster may allow for the identification of human orthologs that similarly mediate toxicity in humans. In order to develop Drosophila melanogaster as a model of dissecting chemotoxicity, we first need to develop standardized high throughput toxicity assays and prove that inter-individual variation in toxicity as measured by such assays is highly heritable. Methods We developed a method for the oral delivery of commonly used chemotherapy drugs to Drosophila. Post-treatment female fecundity displayed a dose dependent response to varying levels of the chemotherapy drug delivered. We fixed the dose for each drug at a level that resulted in a 50% reduction in fecundity and used a paternal half-sibling heritability design to calculate the heritability attributable to chemotherapy toxicity assayed via a decrease in female fecundity. Chemotherapy agents tested were carboplatin, floxuridine, gemcitabine hydrochloride, methotrexate, mitomycin C, and topotecan hydrochloride. Results We found that six currently widely prescribed chemotherapeutic agents lowered fecundity in D. melanogaster in both a dose dependent and highly heritable manner. The following heritability estimates were found: carboplatin – 0.72, floxuridine – 0.52, gemcitabine hydrochloride – 0.72, methotrexate – 0.99, mitomycin C – 0.64, and topotecan hydrochloride – 0.63. Conclusions The high heritability estimates observed in this study, irrespective of the particular class of drug examined, suggest that human toxicity may also have a sizable genetic component. PMID:22336958

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

Chemotherapy-induced damage to ovary: mechanisms and clinical impact.

PubMed

Bedoschi, Giuliano; Navarro, Paula Andrea; Oktay, Kutluk

2016-10-01

Cancer is a major public health problem around the world. Currently, about 5% of women diagnosed with cancer are of reproductive age. These young survivors may face compromised fertility. The effects of chemotherapeutic agents on ovarian reserve and its clinical consequences are generally inferred from a variety of surrogate markers of ovarian reserve, all aiming to provide prognostic information on fertility or the likelihood of success of infertility treatment. Until recently, the mechanisms that are responsible for chemotherapy-induced ovarian damage were not fully elucidated. The understanding of these mechanisms may lead to targeted treatments to preserve fertility. In this manuscript, we will review the current knowledge on the mechanism of ovarian damage and clinical impact of chemotherapy agents on fertility.

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'. © 2017 The Author(s).

[Chemotherapy-induced acral erythema: a clinical and histopathologic study of 44 cases].

PubMed

Hueso, L; Sanmartín, O; Nagore, E; Botella-Estrada, R; Requena, C; Llombart, B; Serra-Guillén, C; Alfaro-Rubio, A; Guillén, C

2008-05-01

Acral erythema, also known as palmoplantar erythrodysesthesia or hand-foot syndrome, is a relatively common cutaneous reaction caused by a variety of chemotherapeutic agents. It presents during cancer treatment as painful erythema and paresthesia affecting the palms and soles. It seems to be dose dependent and its appearance is determined by both the peak plasma concentration and the cumulative dose of the chemotherapeutic agent. The symptoms and histopathology findings are suggestive of direct cytotoxicity affecting the epidermis of the extremities caused by high concentrations of chemotherapeutic agents. The most commonly implicated agents are doxorubicin, 5-fluoracil and its derivatives, cytarabine, and docetaxel. We present the clinical and histologic characteristics of a series of patients diagnosed with chemotherapy-induced acral erythema. The study included all patients who developed acral erythema lesions following chemotherapy between January 2000 and December 2003. Out of 2186 patients who underwent chemotherapy, 44 cases of acral erythema were identified, representing an incidence of 2.01 % during the study period and 16.75 % of all cutaneous lesions attributed to chemotherapy. The most commonly implicated drug was 5-fluoracil administered by continuous infusion and the highest incidence was observed in patients treated with liposomal doxorubicin. Acral erythema was a dose-limiting toxic effect in 29.5 % of cases. The histologic findings varied according to the clinical severity of the lesions and included interface dermatitis with variable keratinocyte necrosis, dilation of the superficial vascular plexus, and limited inflammatory infiltrate. The most commonly used treatment was pyridoxine, along with topical treatments such as cold compresses, emollients, and topical corticosteroids.

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).

Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.

PubMed

Inui, Naoki

2017-05-01

Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.

Potential mechanisms for chemotherapy-induced impairments in cognitive function.

PubMed

Jansen, Catherine; Miaskowski, Christine; Dodd, Marilyn; Dowling, Glenna; Kramer, Joel

2005-11-03

To review the domains of cognitive function and their corresponding neuroanatomic structures as well as present current evidence for neurotoxicity associated with specific chemotherapeutic agents and potential mechanisms for chemotherapy-induced cognitive impairments. Published research articles, review articles, and textbooks. Chemotherapy does not appear to cross the blood-brain barrier when given in standard doses; however, many chemotherapy drugs have the potential to cause cognitive impairments through more than one mechanism. In addition, patient factors may be protective or place individuals at higher risk for cognitive impairments. Although evidence of chemotherapy-induced impairments in cognitive function exists, no clinical studies have attempted to elucidate the mechanisms for chemotherapy-induced impairments in cognitive function. In addition, further studies are needed to determine predictive factors, potential biomarkers, and relevant assessment parameters. The ability to identify high-risk patients has important implications for practice in regard to informed consent, patient education about the effects of treatment, and preventive strategies.

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

2017-12-01

Objectives 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. Methods 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. Results Out of the 68 patients enrolled into the oral chemotherapy

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Pre-treatment anxiety is associated with persistent chemotherapy-induced peripheral neuropathy in women treated with neoadjuvant chemotherapy for breast cancer.

PubMed

Lee, Kwang-Min; Jung, Dooyoung; Hwang, Heesung; Son, Kyung-Lak; Kim, Tae-Yong; Im, Seock-Ah; Lee, Kyung-Hun; Hahm, Bong-Jin

2018-05-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse reaction caused by chemotherapeutic agents, especially the taxanes. CIPN can persist from months to years after completion of chemotherapy, decreasing quality of life for cancer survivors. The aim of this study was to explore the incidence and risk factors of persistent CIPN among women with breast cancer receiving neoadjuvant chemotherapy. In this prospective study, we recruited women with breast cancer receiving neoadjuvant chemotherapy, including four cycles of docetaxel. Participants reported neuropathic symptoms of tingling/numbness at baseline, at the end of chemotherapy treatment, and at 8 months after completion of chemotherapy. Candidate factors associated with CIPN were assessed before chemotherapy. Among 111 participants, 50 (45.0%) experienced CIPN during chemotherapy, and 21 (18.9%) reported persistent CIPN after chemotherapy. Univariate logistic regression analysis revealed that development of CIPN was significantly associated with pre-treatment numbness (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.09-7.40; p = .033), and persistent CIPN was significantly associated with pre-treatment numbness (OR, 3.60; 95% CI, 1.12-11.61; p = .032) and pre-treatment anxiety (OR, 5.02; 95% CI, 1.84-13.70; p = .002). Multivariate analysis indicated that pre-treatment anxiety remained significantly associated with persistent CIPN (OR, 4.01; 95% CI, 1.25-12.87; p = .020). Our results suggested that pre-treatment anxiety might be related to a patient's risk for persistent CIPN in women with breast cancer undergoing neoadjuvant chemotherapy. Further research is required to investigate if interventions targeting pre-treatment anxiety could provide prevention and management for persistent CIPN. Copyright © 2018. Published by Elsevier Inc.

Chemotherapy-induced nausea and vomiting in Asian women with breast cancer receiving anthracycline-based adjuvant chemotherapy.

PubMed

Bourdeanu, Laura; Frankel, Paul; Yu, Wai; Hendrix, Gregory; Pal, Sumanta; Badr, Lina; Somlo, George; Luu, Thehang

2012-01-01

Chemotherapy-induced nausea and vomiting (CINV) remain among the most frequently reported distressing side effects associated with anthracycline-based chemotherapy despite significant advances in antiemetic management. The main risk factor for severity of CINV is the emetogenic potential of the chemotherapeutic agents. However, patient-related risk factors have been identified, including genetic makeup. Although studies have noted that ethnicity influences nausea and vomiting in other contexts, there is a paucity of research regarding the impact of ethnicity on CINV. This study was undertaken to evaluate whether Asian women receiving anthracycline-based chemotherapy experience more CINV than non-Asians. A retrospective, comparative, correlational chart review was performed to abstract the relevant variables. Data from a convenience sample of 358 women with breast cancer who received chemotherapy with doxorubicin between 2004 and 2008 at City of Hope in Duarte, California, were evaluated. The sample consisted of Caucasians (45%), Hispanics (27.7%), Asians (19.8%), and African Americans (7.5%). The results indicate that Asian women with breast cancer undergoing anthracycline-based chemotherapy experienced statistically significantly more clinically important CINV than their non-Asian counterparts. The data were collected retrospectively, with a certain population distribution at a specific time. This study provides interesting preliminary evidence that Asian ethnicity plays a role in the development of severe CINV. When managing chemotherapy toxicities in women with breast cancer, health-care providers should tailor therapy to individual risk profiles. Specifically, consideration of antiemetic therapy should accommodate patient characteristics, such as Asian descent. Copyright © 2012 Elsevier Inc. All rights reserved.

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

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

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.

Efficacy and toxicity of the combination chemotherapy of thalidomide, alkylating agent, and steroid for relapsed/refractory myeloma patients: a report from the Korean Multiple Myeloma Working Party (KMMWP) retrospective study.

PubMed

Kwon, Jihyun; Min, Chang-Ki; Kim, Kihyun; Han, Jae-Joon; Moon, Joon Ho; Kang, Hye Jin; Eom, Hyeon-Seok; Kim, Min Kyoung; Kim, Hyo Jung; Yoon, Dok Hyun; Lee, Jeong-Ok; Lee, Won Sik; Lee, Jae Hoon; Lee, Je-Jung; Choi, Yoon-Seok; Kim, Sung Hyun; Yoon, Sung-Soo

2017-01-01

We analyzed the treatment responses, toxicities, and survival outcomes of patients with relapsed or refractory multiple myeloma who received daily thalidomide, cyclophosphamide, and dexamethasone (CTD) or daily thalidomide, melphalan, and prednisolone (MTP) at 17 medical centers in Korea. Three-hundred and seventy-six patients were enrolled. The combined chemotherapy of thalidomide, corticosteroid, and an alkylating agent (TAS) was second-line chemotherapy in 142 (37.8%) patients, and third-line chemotherapy in 135 (35.9%) patients. The response rate overall was 69.4%. Patients who were not treated with bortezomib and lenalidomide before TAS showed a higher response rate compared to those who were exposed to these agents. The estimated median progression-free survival and overall survival times were 10.4 months and 28.0 months, respectively. The adverse events during TAS were generally tolerable, but 39 (10.4%) patients experienced severe infectious complications. There were no differences in terms of efficacy between CTD and MTP, but infectious complications were more common in CTD group. TAS is an effective treatment regimen which induces a high response rate in relapsed or refractory multiple myeloma patients. Due to the high incidence of grade 3 or 4 infection, proper management of infection is necessary during the TAS treatment, especially the CTD. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Acupressure bands do not improve chemotherapy-induced nausea control in pediatric patients receiving highly emetogenic chemotherapy: A single-blinded, randomized controlled trial.

PubMed

Dupuis, L Lee; Kelly, Kara M; Krischer, Jeffrey P; Langevin, Anne-Marie; Tamura, Roy N; Xu, Ping; Chen, Lu; Kolb, E Anders; Ullrich, Nicole J; Sahler, Olle Jane Z; Hendershot, Eleanor; Stratton, Ann; Sung, Lillian; McLean, Thomas W

2018-03-15

Chemotherapy-induced nausea and vomiting remain common, distressing side effects of chemotherapy. It has been reported that acupressure prevents chemotherapy-induced nausea in adults, but it has not been well studied in children. In this multicenter, prospective, randomized, single-blind, sham-controlled trial, the authors compared acute-phase nausea severity in patients ages 4 to 18 years who were receiving highly emetic chemotherapy using standard antiemetic agents combined with acupressure wrist bands, the most common type of acupressure, versus sham bands. Patients wore acupressure or sham bands continuously on each day of chemotherapy and for up to 7 days afterward. Chemotherapy-induced nausea severity in the delayed phase and chemotherapy-induced vomiting control in the acute and delayed phases also were compared. Of the 187 patients randomized, 165 contributed nausea severity assessments during the acute phase. Acupressure bands did not reduce the severity of chemotherapy-induced nausea in the acute phase (odds ratio [OR], 1.33; 95% confidence limits, 0.89-2.00, in which an OR <1.00 favored acupressure) or in the delayed phase (OR, 1.23; 95% CL, 0.75-2.01). Furthermore, acupressure bands did not improve daily vomiting control during the acute phase (OR, 1.57; 95% CL, 0.95-2.59) or the delayed phase (OR, 0.84; 95% CL, 0.45-1.58). No serious adverse events were reported. Acupressure bands were safe but did not improve chemotherapy-induced nausea or vomiting in pediatric patients who were receiving highly emetic chemotherapy. Cancer 2018;124:1188-96. © 2017 American Cancer Society. © 2017 American Cancer Society.

Effect of Herbal Therapy to Intensity Chemotherapy-Induced Nausea and Vomiting in Cancer Patients.

PubMed Central

Montazeri, Akram Sadat; Raei, Mehdi; Ghanbari, Atefeh; Dadgari, Ali; Montazeri, Azam Sadat; Hamidzadeh, Azam

2013-01-01

Background: Chemotherapy-induced nausea and vomiting are the most important complications for cancer patients as its prevalence has been reported to be about 54-96 percent. ginger has been used for medicinal purposes including nausea and vomiting in traditional Persian, Chinese and Indian pharmacopoeia. Objectives: The objective of this study was to evaluate the efficacy of complimentary ginger among cancer patients experiencing nausea and vomiting. Material and Methods: A randomized cross-over clinical trial was carried out on patients under chemotherapy treatment for at least 2 episodes of chemotherapy and at least 2 episodes of previous experience of nausea and vomiting. Subjects of this study received 2 different complementary regimes with 250mg ginger capsule in regime A and placebo capsule in regime B. subjects of the study were crossed over to receive the other regime during the two cycles of chemotherapy. Results: Findings of the study indicated that subjects receiving ginger showed significant reduction in frequency and intensity of nausea and vomiting compared to placebo receiving subjects. Conclusions: According to finding of this study, in accordance to most of other researches, ginger is an effective agent to reduce chemotherapy-induced nausea and vomiting. However, there are some researches supporting ginger as a moderate antiemetic agent among cancerous patients under chemotherapy. PMID:24693415

Reviewing current and emerging antiemetics for chemotherapy-induced nausea and vomiting prophylaxis.

PubMed

Natale, James J

2015-01-01

This review provides background information on chemotherapy-induced nausea and vomiting (CINV) classification and pathophysiology and reviews various antiemetic agents for CINV prophylaxis, including corticosteroids, serotonin receptor antagonists (5-HT3 RAs), tachykinin NK1 receptor antagonists (NK1 RAs), and olanzapine. Other less commonly used agents are briefly discussed. Practical considerations are reviewed as well, including emetogenicity of chemotherapeutic regimens, patient-specific risk factors for CINV, principles of CINV management, health economics outcome research, and quality of life. Available data on the newly FDA-approved antiemetic combination netupitant/palonosetron (NEPA) is also reviewed. Prevention of CINV is an important goal in managing patients with cancer and is especially difficult with respect to nausea and delayed CINV. Corticosteroids are a mainstay of CINV prophylaxis and are usually given in combination with other therapies. The 5-HT3 RA palonosetron has shown increased efficacy over other agents in the same class for prevention of delayed emesis with moderately emetogenic chemotherapy and NK1 RAs improve emesis prevention in combination with 5-HT3 RAs and dexamethasone. Olanzapine has shown efficacy for CINV prophylaxis and the treatment of breakthrough CINV. The new combination therapy, NEPA, has been shown to be efficacious for the prevention of acute, delayed, and overall CINV. Risk factors that have been identified for CINV include gender, age, and alcohol intake. It is important to assess the emetogenicity of chemotherapy regimens as well as the potential impact of patient risk factors in order to provide adequate prophylaxis. Acute and delayed CINV are severe, burdensome side effects of chemotherapy; however, new data on prevention and the discovery of new agents can further improve CINV control.

Chemotherapy inhibits skeletal muscle ubiquitin-proteasome-dependent proteolysis.

PubMed

Tilignac, Thomas; Temparis, Sandrine; Combaret, Lydie; Taillandier, Daniel; Pouch, Marie-Noëlle; Cervek, Matjaz; Cardenas, Diana M; Le Bricon, Thierry; Debiton, Eric; Samuels, Susan E; Madelmont, Jean-Claude; Attaix, Didier

2002-05-15

Chemotherapy has cachectic effects, but it is unknown whether cytostatic agents alter skeletal muscle proteolysis. We hypothesized that chemotherapy-induced alterations in protein synthesis should result in the increased incidence of abnormal proteins, which in turn should stimulate ubiquitin-proteasome-dependent proteolysis. The effects of the nitrosourea cystemustine were investigated in skeletal muscles from both healthy and colon 26 adenocarcinoma-bearing mice, an appropriate model for testing the impact of cytostatic agents. Muscle wasting was seen in both groups of mice 4 days after a single cystemustine injection, and the drug further increased the loss of muscle proteins already apparent in tumor-bearing animals. Cystemustine cured the tumor-bearing mice with 100% efficacy. Surprisingly, within 11 days of treatment, rates of muscle proteolysis progressively decreased below basal levels observed in healthy control mice and contributed to the cessation of muscle wasting. Proteasome-dependent proteolysis was inhibited by mechanisms that include reduced mRNA levels for 20S and 26S proteasome subunits, decreased protein levels of 20S proteasome subunits and the S14 non-ATPase subunit of the 26S proteasome, and impaired chymotrypsin- and trypsin-like activities of the enzyme. A combination of cisplatin and ifosfamide, two drugs that are widely used in the treatment of cancer patients, also depressed the expression of proteasomal subunits in muscles from rats bearing the MatB adenocarcinoma below basal levels. Thus, a down-regulation of ubiquitin-proteasome-dependent proteolysis is observed with various cytostatic agents and contributes to reverse the chemotherapy-induced muscle wasting.

Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases.

PubMed

Shah, Neal; Mohammad, Afroz S; Saralkar, Pushkar; Sprowls, Samuel A; Vickers, Schuyler D; John, Devin; Tallman, Rachel M; Lucke-Wold, Brandon P; Jarrell, Katherine E; Pinti, Mark; Nolan, Richard L; Lockman, Paul R

2018-03-28

In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2 + BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

[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.

Chemotherapy-Induced Peripheral Neuropathy: A Current Review

PubMed Central

Staff, Nathan P.; Grisold, Anna; Grisold, Wolfgang; Windebank, Anthony J.

2017-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting side effect experienced by patients receiving treatment for cancer. Approximately 30–40% of patients treated with neurotoxic chemotherapy will develop CIPN and there is considerable variability in its severity between patients. It is often sensory-predominant with pain and can lead to long-term morbidity in survivors. The prevalence and burden of CIPN late effects will likely increase as cancer survival rates continue to improve. In this review, we discuss the approach to peripheral neuropathy in patients with cancer and address the clinical phenotypes and pathomechanisms of specific neurotoxic chemotherapeutic agents. PMID:28486769

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.

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.

A novel rat model for chemotherapy-induced alopecia.

PubMed

Wikramanayake, T C; Amini, S; Simon, J; Mauro, L M; Elgart, G; Schachner, L A; Jimenez, J J

2012-04-01

More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy-induced alopecia (CIA), a side-effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA. To develop a clinically relevant adult rat model for CIA. We first tested whether neonatal pigmented Long-Evans (LE) rats developed alopecia in response to the chemotherapeutic agents etoposide and cyclophosphamide. We then determined whether the rats developed CIA as adults. In the latter experiment, rat dorsal hair was clipped during the early telogen stage to synchronize the hair cycle, and starting 15 days later, the rats were treated with etoposide for 3 days. Neonatal LE pups developed CIA in response to etoposide and cyclophosphamide, similar to other murine models for CIA. Clipping of the hair shaft during early telogen resulted in synchronized anagen induction and subsequent alopecia after etoposide treatment in the clipped areas only. Hair follicles in the clipped areas had the typical chemotherapy-induced follicular dystrophy (dystrophic catagen). When the hair in the pigmented alopecic areas regrew, it had normal pigmentation. A novel, pigmented adult rat model has been established for CIA. By hair-shaft clipping during early telogen, synchronized anagen entry was induced, which resulted in alopecia in response to chemotherapy. This is the first clinically relevant adult rat model for CIA, and will be a useful tool to test agents for the prevention and treatment of CIA. © The Author(s). CED © 2012 British Association of Dermatologists.

Metallic taste in cancer patients treated with chemotherapy.

PubMed

IJpma, I; Renken, R J; Ter Horst, G J; Reyners, A K L

2015-02-01

Metallic taste is a taste alteration frequently reported by cancer patients treated with chemotherapy. Attention to this side effect of chemotherapy is limited. This review addresses the definition, assessment methods, prevalence, duration, etiology, and management strategies of metallic taste in chemotherapy treated cancer patients. Literature search for metallic taste and chemotherapy was performed in PubMed up to September 2014, resulting in 184 articles of which 13 articles fulfilled the inclusion criteria: English publications addressing metallic taste in cancer patients treated with FDA-approved chemotherapy. An additional search in Google Scholar, in related articles of both search engines, and subsequent in the reference lists, resulted in 13 additional articles included in this review. Cancer patient forums were visited to explore management strategies. Prevalence of metallic taste ranged from 9.7% to 78% among patients with various cancers, chemotherapy treatments, and treatment phases. No studies have been performed to investigate the influence of metallic taste on dietary intake, body weight, and quality of life. Several management strategies can be recommended for cancer patients: using plastic utensils, eating cold or frozen foods, adding strong herbs, spices, sweetener or acid to foods, eating sweet and sour foods, using 'miracle fruit' supplements, and rinsing with chelating agents. Although metallic taste is a frequent side effect of chemotherapy and a much discussed topic on cancer patient forums, literature regarding metallic taste among chemotherapy treated cancer patients is scarce. More awareness for this side effect can improve the support for these patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

Biological therapy of hematologic malignancies: toward a chemotherapy-free era.

PubMed

Klener, Pavel; Etrych, Tomas; Klener, Pavel

2017-10-06

Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short. Despite great successes, however, conventional genotoxic cytostatics suffered from an inherently narrow therapeutic index and extensive toxicity, which in many instances limited their clinical utilization. In the last decade of the 20th century, increasing knowledge on the biology of certain malignancies resulted in the conception and development of first molecularly targeted agents designed to inhibit specific druggable molecules involved in the survival of cancer cells. Advances in technology and genetic engineering enabled the production of structurally complex anticancer macromolecules called biologicals, including therapeutic monoclonal antibodies, antibody-drug conjugates and antibody fragments. The development of drug delivery systems (DDSs), in which conventional drugs were attached to various types of carriers including nanoparticles, liposomes or biodegradable polymers, represented an alternative approach to the development of new anticancer agents. Despite the fact that the antitumor activity of drugs attached to DDSs was not fundamentally different, the improved pharmacokinetic profiles, decreased toxic side effects and significantly increased therapeutic indexes resulted in their enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint

Chemotherapy-induced bystander effect in response to several chloroethylnitrosoureas: an origin independent of DNA damage?

PubMed

Merle, Patrick; Morvan, Daniel; Caillaud, Denis; Demidem, Aicha

2008-01-01

Chloroethylnitrosourea (CENU) chemotherapy is used for the treatment of melanoma tumors. The main mechanism of action of this anticancer agent is via DNA damage. We recently showed in murine experiments using a parental double B16 melanoma tumor model that, after treatment of primary tumors with cystemustine (CENU agent), untreated secondary tumors exhibited growth inhibition and metabolism disorders. The response of secondary untreated tumor was called the chemotherapy-induced bystander effect. To see whether chemotherapy-induced bystander effects were induced with other members of the CENU family, we compared three CENU(s) used in melanoma treatment: cystemustine, carmustine and fotemustine. Our results demonstrate that fotemustine, like cystemustine, but not carmustine induced a protective effect against secondary untreated tumors including alterations in phospholipid derivative and glutathione which are the metabolic signature of the bystander effect. From these data we may conclude that DNA damage to the primary tumor is not sufficient to explain chemotherapy-induced bystander effects.

Treatment of a Solid Tumor Using Engineered Drug-Resistant Immunocompetent Cells and Cytotoxic Chemotherapy

PubMed Central

Dasgupta, Anindya; Shields, Jordan E.

2012-01-01

Abstract Multimodal therapy approaches, such as combining chemotherapy agents with cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector cells. Overcoming such toxic effects of anticancer cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of immunocompetent cells, thereby allowing for the coadministration of cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into immunocompetent cells. In the present study, we evaluated a DRI-based strategy that incorporates the immunocompetent cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector cells efficiently lysed neuroblastoma cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant cellular therapy when combined with cytotoxic chemotherapy approaches. PMID:22397715

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.

Chemotherapy following radium‐223 dichloride treatment in ALSYMPCA

PubMed Central

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

2016-01-01

BACKGROUND 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. METHODS 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. RESULTS 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

Febrile neutropenia in cats treated with chemotherapy.

PubMed

Pierro, J; Krick, E; Flory, A; Regan, R; DeRegis, C; Boudreaux, B; Barber, L; Saam, D; Saba, C

2017-06-01

The purpose of this study was to describe the clinical presentation, potential causative agents, treatment and outcome of febrile neutropenia (FN) in chemotherapy-treated cats. Medical records from eight institutions were retrospectively reviewed. A total of 22 FN events in 20 cats were evaluated. Lymphoma was the most common cancer diagnosis; lomustine and vinca alkaloids were the most frequently implicated causative agents. Presenting clinical signs included decreased appetite, lethargy, vomiting and diarrhoea. Median body temperature and absolute neutrophil count at presentation were 104.1 °F; 40 °C (range: 103.1-105.1 °F; 39.5-40.6 °C) and 246 mL -1 (range: 0-1600 mL -1 ), respectively. Median number of days between chemotherapy administration and FN onset was 5 (range: 4-25 days). All but one cat were treated with intravenous fluids and broad spectrum antibiotics. Fevers resolved in all cases and absolute neutrophil counts returned to normal in 19 cats. Clinical presentation of cats with FN appears similar to that of dogs. © 2016 John Wiley & Sons Ltd.

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.

Occupational Exposure to Chemotherapy of Pharmacy Personnel at a Single Centre

PubMed Central

Ramphal, Raveena; Bains, Tejinder; Goulet, Geneviève; Vaillancourt, Régis

2015-01-01

Background: Cyclophosphamide is one of the most commonly used chemotherapy drugs worldwide. Data concerning environmental contamination and biological exposure of pharmacy personnel to this and other chemotherapy drugs are limited. Objectives: To determine whether pharmacy personnel involved in preparing and checking cyclophosphamide doses were more likely to have detectable levels of this drug in their urine than non-oncology pharmacy personnel with no known contact with the drug, and to compare the degree of surface contamination with cyclophosphamide, methotrexate, and ifosfamide in the oncology pharmacy of a tertiary care pediatric hospital, where chemotherapy doses were prepared, and the main (control) pharmacy in the same institution, where no chemotherapy was prepared. Methods: Biological exposure to cyclophosphamide was compared between pharmacy personnel who did and did not handle this drug by determining whether participants had detectable amounts of cyclophosphamide in their urine. Environmental exposure to chemotherapy drugs was assessed by using surface wipes to determine the degree of surface contamination with various chemotherapy agents in the oncology pharmacy and the main (control) pharmacy. Results: On initial testing, cyclophosphamide was detected in the urine of all pharmacy personnel (n = 7 oncology personnel, n = 5 control personnel). However, it was determined that all control personnel had been exposed to the oncology pharmacy on the day of testing. Repeat testing of these individuals revealed no positive samples among those not exposed to the oncology pharmacy on the day of repeat testing. The sole positive result on retesting of control personnel was for a participant who had been exposed to the oncology pharmacy on the retest day. Surface wipe testing revealed contamination of the oncology pharmacy with cyclophosphamide and methotrexate before and after cleaning, as well as contamination with ifosfamide after cleaning. The main (control

A survey of the sequence-specific interaction of damaging agents with DNA: emphasis on antitumor agents.

PubMed

Murray, V

1999-01-01

This article reviews the literature concerning the sequence specificity of DNA-damaging agents. DNA-damaging agents are widely used in cancer chemotherapy. It is important to understand fully the determinants of DNA sequence specificity so that more effective DNA-damaging agents can be developed as antitumor drugs. There are five main methods of DNA sequence specificity analysis: cleavage of end-labeled fragments, linear amplification with Taq DNA polymerase, ligation-mediated polymerase chain reaction (PCR), single-strand ligation PCR, and footprinting. The DNA sequence specificity in purified DNA and in intact mammalian cells is reviewed for several classes of DNA-damaging agent. These include agents that form covalent adducts with DNA, free radical generators, topoisomerase inhibitors, intercalators and minor groove binders, enzymes, and electromagnetic radiation. The main sites of adduct formation are at the N-7 of guanine in the major groove of DNA and the N-3 of adenine in the minor groove, whereas free radical generators abstract hydrogen from the deoxyribose sugar and topoisomerase inhibitors cause enzyme-DNA cross-links to form. Several issues involved in the determination of the DNA sequence specificity are discussed. The future directions of the field, with respect to cancer chemotherapy, are also examined.

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.

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy.

PubMed

Oh, Sang-Bo; Park, Sung-Woo; Chung, Joo-Seop; Lee, Won-Sik; Lee, Ho-Seop; Cho, Su-Hee; Choi, Yoon-Suk; Lim, Sung-Nam; Shin, Ho-Jin

2017-11-01

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.

Nicotine Induces Resistance to Chemotherapy by Modulating Mitochondrial Signaling in Lung Cancer

PubMed Central

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D.; Upadhyay, Daya

2009-01-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 μM) followed by cisplatin (35 μM) plus etoposide (20 μM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4′diisothiocyanatostilbene-2,2′disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-ρ0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer

Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

PubMed

Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

2009-02-01

Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer

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.

Real-world utilization of darbepoetin alfa in cancer chemotherapy patients.

PubMed

Pan, Xiaoyun Lucy; Nordstrom, Beth L; MacLachlan, Sharon; Lin, Junji; Xu, Hairong; Sharma, Anjali; Chandler, David; Li, Xiaoyan Shawn

2017-01-01

Objectives To provide an understanding of darbepoetin alfa dose patterns in cancer patients undergoing myelosuppressive chemotherapy starting from 2011. Study design This is a retrospective cohort study using a proprietary outpatient oncology database. Methods Metastatic, solid tumor cancer patients receiving concomitant myelosuppressive chemotherapy and darbepoetin alfa with an associated hemoglobin <10 g/dL during 2011-2015 were identified. The analysis was restricted to the first continuous exposure to chemotherapy agents (maximum allowable gap of 90 days between consecutive exposures) with darbepoetin alfa for each eligible patient. Initial, maintenance, weekly, and cumulative doses of darbepoetin alfa were examined across all darbepoetin alfa users. Subgroup analyses were conducted by chemotherapy type, baseline hemoglobin level, year of chemotherapy, solid tumor type, and initial dosing schedule. Differences in weekly doses across subgroups were evaluated using Wilcoxon rank-sum tests. Results Among 835 eligible patients, over 90% were 50 years or older. Mean chemotherapy course duration was 248 days, and mean duration of darbepoetin alfa treatment was 106 days. The mean weekly darbepoetin alfa dose was 110 µg. Patients received a mean of 4.3 darbepoetin alfa injections in the first chemotherapy course. There were no statistically significant differences (all P values > .05) in weekly dose by chemotherapy type, baseline hemoglobin level, year of chemotherapy, or solid tumor type. Conclusion The average weekly darbepoetin alfa dose among metastatic cancer patients with chemotherapy-induced anemia from this study was 110 µg, which was lower than the labeled dosage for most adults. This estimate did not differ over time, across chemotherapy regimens, baseline hemoglobin levels, or solid tumor types.

Prediction of Therapeutic Effect of Chemotherapy for NSCLC Using Dual-Input Perfusion CT Analysis: Comparison among Bevacizumab Treatment, Two-Agent Platinum-based Therapy without Bevacizumab, and Other Non-Bevacizumab Treatment Groups.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Iwama, Eiji; Okamoto, Isamu; Kamitani, Takeshi; Sagiyama, Koji; Yamasaki, Yuzo; Honda, Hiroshi

2018-02-01

Purpose To determine whether dual-input perfusion computed tomography (CT) can predict therapeutic response and prognosis in patients who underwent chemotherapy for non-small cell lung cancer (NSCLC). Materials and Methods The institutional review board approved this study and informed consent was obtained. Sixty-six patients with stage III or IV NSCLC (42 men, 24 women; mean age, 63.4 years) who underwent chemotherapy were enrolled. Patients were separated into three groups: those who received chemotherapy with bevacizumab (BV) (n = 20), those who received two-agent platinum-based therapy without BV (n = 25), and those who received other non-BV treatment (n = 21). Before treatment, pulmonary artery perfusion (PAP) and bronchial artery perfusion (BAP) of the tumors were calculated. Predictors of tumor reduction after two courses of chemotherapy and prognosis were identified by using univariate and multivariate analyses. Covariates included were age, sex, patient's performance status, baseline maximum diameter of the tumor, clinical stage, pretreatment PAP, and pretreatment BAP. For multivariate analyses, multiple linear regression analysis for tumor reduction rate and Cox proportional hazards model for prognosis were performed, respectively. Results Pretreatment BAP was independently correlated with tumor reduction rate after two courses of chemotherapy in the BV treatment group (P = .006). Pretreatment BAP was significantly associated with a highly cumulative risk of death (P = .006) and disease progression after chemotherapy (P = .015) in the BV treatment group. Pretreatment PAP and clinical parameters were not significant predictors of therapeutic effect or prognosis in three treatment groups. Conclusion Pretreatment BAP derived from dual-input perfusion CT seems to be a promising tool to help predict responses to chemotherapy with BV in patients with NSCLC. © RSNA, 2017.

Extravasation of antineoplastic agents: prevention and treatments.

PubMed

Boschi, Rita; Rostagno, Elena

2012-07-31

The extravasation of antineoplastic agents is an unwanted and distressing situation that can easily occur. It may cause severe and irreversible local injuries. Left untreated, vesicant chemotherapy extravasation can potentially cause tissue necrosis, functional impairment and permanent disfigurement. This article provides a review of current literature regarding recommendations on the prevention and treatment of extravasation of antineoplastic agents.

Oculomotor Deficits after Chemotherapy in Childhood

PubMed Central

Einarsson, Einar-Jón; Patel, Mitesh; Petersen, Hannes; Wiebe, Thomas; Magnusson, Måns; Moëll, Christian; Fransson, Per-Anders

2016-01-01

Advances in the diagnosis and treatment of pediatric malignancies have substantially increased the number of childhood cancer survivors. However, reports suggest that some of the chemotherapy agents used for treatment can cross the blood brain barrier which may lead to a host of neurological symptoms including oculomotor dysfunction. Whether chemotherapy at young age causes oculomotor dysfunction later in life is unknown. Oculomotor performance was assessed with traditional and novel methods in 23 adults (mean age 25.3 years, treatment age 10.2 years) treated with chemotherapy for a solid malignant tumor not affecting the central nervous system. Their results were compared to those from 25 healthy, age-matched controls (mean age 25.1 years). Correlation analysis was performed between the subjective symptoms reported by the chemotherapy treated subjects (CTS) and oculomotor performance. In CTS, the temporal control of the smooth pursuit velocity (velocity accuracy) was markedly poorer (p<0.001) and the saccades had disproportionally shorter amplitude than normal for the associated saccade peak velocity (main sequence) (p = 0.004), whereas smooth pursuit and saccade onset times were shorter (p = 0.004) in CTS compared with controls. The CTS treated before 12 years of age manifested more severe oculomotor deficits. CTS frequently reported subjective symptoms of visual disturbances (70%), unsteadiness, light-headedness and that things around them were spinning or moving (87%). Several subjective symptoms were significantly related to deficits in oculomotor performance. To conclude, chemotherapy in childhood or adolescence can result in severe oculomotor dysfunctions in adulthood. The revealed oculomotor dysfunctions were significantly related to the subjects’ self-perception of visual disturbances, dizziness, light-headedness and sensing unsteadiness. Assessments of oculomotor function may, thus, offer an objective method to track and rate the level of neurological

Preventing medication errors in cancer chemotherapy.

PubMed

Cohen, M R; Anderson, R W; Attilio, R M; Green, L; Muller, R J; Pruemer, J M

1996-04-01

Recommendations for preventing medication errors in cancer chemotherapy are made. Before a health care provider is granted privileges to prescribe, dispense, or administer antineoplastic agents, he or she should undergo a tailored educational program and possibly testing or certification. Appropriate reference materials should be developed. Each institution should develop a dose-verification process with as many independent checks as possible. A detailed checklist covering prescribing, transcribing, dispensing, and administration should be used. Oral orders are not acceptable. All doses should be calculated independently by the physician, the pharmacist, and the nurse. Dosage limits should be established and a review process set up for doses that exceed the limits. These limits should be entered into pharmacy computer systems, listed on preprinted order forms, stated on the product packaging, placed in strategic locations in the institution, and communicated to employees. The prescribing vocabulary must be standardized. Acronyms, abbreviations, and brand names must be avoided and steps taken to avoid other sources of confusion in the written orders, such as trailing zeros. Preprinted antineoplastic drug order forms containing checklists can help avoid errors. Manufacturers should be encouraged to avoid or eliminate ambiguities in drug names and dosing information. Patients must be educated about all aspects of their cancer chemotherapy, as patients represent a last line of defense against errors. An interdisciplinary team at each practice site should review every medication error reported. Pharmacists should be involved at all sites where antineoplastic agents are dispensed. Although it may not be possible to eliminate all medication errors in cancer chemotherapy, the risk can be minimized through specific steps. Because of their training and experience, pharmacists should take the lead in this effort.

Chemotherapy Extravasation: Establishing a National Benchmark for Incidence Among Cancer Centers.

PubMed

Jackson-Rose, Jeannette; Del Monte, Judith; Groman, Adrienne; Dial, Linda S; Atwell, Leah; Graham, Judy; O'Neil Semler, Rosemary; O'Sullivan, Maryellen; Truini-Pittman, Lisa; Cunningham, Terri A; Roman-Fischetti, Lisa; Costantinou, Eileen; Rimkus, Chris; Banavage, Adrienne J; Dietz, Barbara; Colussi, Carol J; Catania, Kimberly; Wasko, Michelle; Schreffler, Kevin A; West, Colleen; Siefert, Mary Lou; Rice, Robert David

2017-08-01

Given the high-risk nature and nurse sensitivity of chemotherapy infusion and extravasation prevention, as well as the absence of an industry benchmark, a group of nurses studied oncology-specific nursing-sensitive indicators. 
. The purpose was to establish a benchmark for the incidence of chemotherapy extravasation with vesicants, irritants, and irritants with vesicant potential.
. Infusions with actual or suspected extravasations of vesicant and irritant chemotherapies were evaluated. Extravasation events were reviewed by type of agent, occurrence by drug category, route of administration, level of harm, follow-up, and patient referrals to surgical consultation.
. A total of 739,812 infusions were evaluated, with 673 extravasation events identified. Incidence for all extravasation events was 0.09%.

Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia.

PubMed

Chamberlain, Marc C; Raizer, Jeffrey

2009-06-01

A case series of gliomas treated with alkylator-based chemotherapy who subsequently developed myelodysplastic syndrome (tMDS) or acute myelocytic leukemia (AML). Alkylator-based chemotherapy is recognized to be leukemogenic; however, it is infrequently described as a delayed consequence of anti-glioma treatment. Seven patients (4 men; 3 women) ages 34-69 years (median 44), with gliomas (3 Grade 2; 4 Grade 3) were treated with surgery, all but one with involved-field radiotherapy and all with alkylator-based chemotherapy (temozolomide; 6 patients, nitrosoureas; 5 patients, both agents; 5 patients). Exposure to alkylator-based chemotherapy ranged from 8 to 30 months (median 24). The diagnosis of tMDS was determined by bone marrow biopsy in 7 patients. Seven patients showed chromosomal abnormalities consistent with chemotherapy induced MDS. Three patients were diagnosed with AML as well (in two determined by bone marrow and one at autopsy). Interval from last chemotherapy exposure to diagnosis of tMDS/AML ranged from 3 to 31 months (median 24 months). Two patients were treated with bone marrow transplantation and 5 received supportive care only. Five patients have died, 2 as a consequence of recurrent brain tumor, 1 as a complication of transplantation, and 2 due to AML. Although rare, induction of tMDS/AML following extended use of alkylator-based chemotherapy may become more relevant with the evolving practice to treat gliomas for protracted periods. Future work to determine at risk patients would be important.

Palonosetron (Aloxi): a second-generation 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting

PubMed Central

2006-01-01

In July 2003, the Food and Drug Administration approved palonosetron hydrochloride injection for the treatment of chemotherapy-induced nausea and vomiting (CINV). The newest agent in the class of 5-HT3 receptor antagonists (5-HT3RAs), palonosetron differs from other agents in its class by its higher receptor-binding affinity and longer half-life. These pharmacological properties have resulted in improved antiemetic activity in clinical trials, particularly in the treatment of delayed CINV following moderate emetogenic chemotherapy. Based on the results of these clinical studies, palonosetron is the only 5-HT3RA approved for delayed CINV. Palonosetron is given as a single 0.25-mg intravenous dose 30 minutes before the initial dose of chemotherapy. Headache and constipation were the most common adverse events reported with palonosetron therapy. PMID:17106506

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.

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

PubMed

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

2017-08-01

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. Copyright © 2017. Published by Elsevier B.V.

The potential role of bortezomib in combination with chemotherapy and radiation in non-small-cell lung cancer.

PubMed

Edelman, Martin J

2005-10-01

The combination of chemotherapy and radiation has been validated for the treatment of locally advanced non-small-cell lung cancer (NSCLC). However, the results are still unsatisfactory, and there is a need to improve current treatment. One approach is to use new agents that have the potential to enhance the efficacy of chemotherapy, radiation therapy (RT), or both. One potential target is the ubiquitin-proteasome pathway. This pathway plays an essential role in the degradation of most short- and long-lived intracellular proteins in eukaryotic cells and therefore regulating the cell cycle, neoplastic growth, and metastasis. Bortezomib is a selective 26S proteasome inhibitor that has been approved for the treatment of multiple myeloma. Bortezomib has demonstrated in vitro chemotherapy- and RT-sensitizing properties as well as single-agent activity in lung cancer. This article will review the rationale for the use of bortezomib as part of the chemotherapy/RT strategy for the treatment of NSCLC.

Protective Effect of a Mitochondria-Targeted Peptide against the Development of Chemotherapy-Induced Peripheral Neuropathy in Mice.

PubMed

Toyama, Satoshi; Shimoyama, Naohito; Szeto, Hazel H; Schiller, Peter W; Shimoyama, Megumi

2018-04-18

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.

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.

Real-World Effectiveness of Chemotherapy in Elderly Patients With Metastatic Bladder Cancer in the United States.

PubMed

Galsky, Matthew D; Pal, Sumanta Kumar; Lin, Shih-Wen; Ogale, Sarika; Zivkovic, Marko; Simpson, Joseph; Derleth, Christina; Schiff, Christina; Sonpavde, Guru

2018-04-26

Outcomes for patients with metastatic bladder cancer (mBC) are generally poor and progressively worse following first-line (1L) chemotherapy. To evaluate treatment patterns, survival outcomes, and characteristics of a large, real-world US population of elderly patients with advanced mBC receiving 1L and second-line (2L) treatment retrospectively. We identified patients with advanced mBC (aged ≥66 years)-newly diagnosed between January 1, 2004, and December 31, 2011-in the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program-Medicare linked database and assessed their palliative systemic chemotherapy treatments and survival outcomes. Of 1703 eligible patients, 42% received 1L chemotherapy; 1L-treated patients tended to be younger and healthier than nontreated patients. Only 27% of 1L-treated patients received cisplatin-based chemotherapy, most commonly cisplatin-gemcitabine. Cisplatin-treated patients were younger and had fewer comorbidities than non-cisplatin-treated patients. Thirty-five percent of 1L-treated patients subsequently received 2L chemotherapy. Patients received a variety of 2L agents as combination chemotherapy (52%) or single-agent chemotherapy (39%). Median overall survival durations in 1L-treated and 2L-treated patients were 8.5 and 7.9 months, respectively. Results from this retrospective SEER-Medicare database analysis underscore the historical inadequacies of 1L and 2L treatments in elderly patients with advanced mBC. Few patients were treated with 1L chemotherapy, a minority of whom received 1L cisplatin-based chemotherapy, and even fewer received 2L chemotherapy. These findings highlight the disconnect between 1L treatment in clinical trials and treatment in the real-world setting and the lack of standard approaches to 2L treatment in the United States.

Relative susceptibilities of male germ cells to genetic defects induced by cancer chemotherapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wyrobek, A J; Schmid, T E; Marchetti, F

Some chemotherapy regimens include agents that are mutagenic or clastogenic in model systems. This raises concerns that cancer survivors, who were treated before or during their reproductive years, may be at increased risks for abnormal reproductive outcomes. However, the available data from offspring of cancer survivors are limited, representing diverse cancers, therapies, time-to-pregnancies, and reproductive outcomes. Rodent breeding data after paternal exposures to individual chemotherapeutic agents illustrate the complexity of factors that influence the risk for transmitted genetic damage including agent, dose, endpoint, and the germ-cell susceptibility profiles that vary across agents. Direct measurements of chromosomal abnormalities in sperm ofmore » mice and humans by sperm FISH have corroborated the differences in germ-cell susceptibilities. The available evidence suggests that the risk of producing chromosomally defective sperm is highest during the first few weeks after the end of chemotherapy, and decays with time. Thus, sperm samples provided immediately after the initiation of cancer therapies may contain treatment-induced genetic defects that will jeopardize the genetic health of offspring.« less

Dissecting the Impact of Chemotherapy on the Human Hair Follicle

PubMed Central

Bodó, Enikő; Tobin, Desmond J.; Kamenisch, York; Bíró, Tamás; Berneburg, Mark; Funk, Wolfgang; Paus, Ralf

2007-01-01

Chemotherapy-induced alopecia represents one of the major unresolved problems of clinical oncology. The underlying molecular pathogenesis in humans is virtually unknown because of the lack of adequate research models. Therefore, we have explored whether microdissected, organ-cultured, human scalp hair follicles (HFs) in anagen VI can be exploited for dissecting and manipulating the impact of chemotherapy on human HFs. Here, we show that these organ-cultured HFs respond to a key cyclophosphamide metabolite, 4-hydroperoxycyclophosphamide (4-HC), in a manner that resembles chemotherapy-induced HF dystrophy as it occurs in vivo: namely, 4-HC induced melanin clumping and melanin incontinence, down-regulated keratinocyte proliferation, massively up-regulated apoptosis of hair matrix keratinocytes, prematurely induced catagen, and up-regulated p53. In addition, 4-HC induced DNA oxidation and the mitochondrial DNA common deletion. The organ culture system facilitated the identification of new molecular targets for chemotherapy-induced HF damage by microarray technology (eg, interleukin-8, fibroblast growth factor-18, and glypican 6). It was also used to explore candidate chemotherapy protectants, for which we used the cytoprotective cytokine keratinocyte growth factor as exemplary pilot agent. Thus, this novel system serves as a powerful yet pragmatic tool for dissecting and manipulating the impact of chemotherapy on the human HF. PMID:17823286

Novel therapeutic agents for osteosarcoma.

PubMed

O'Day, Kathleen; Gorlick, Richard

2009-04-01

Osteosarcoma is the most common malignant primary bone tumor in childhood. Despite multiagent chemotherapy and aggressive surgical resection, 30% of patients with localized disease and 80% of patients with metastatic disease at diagnosis will relapse. Survival for these patients has remained unchanged over the past 20 years. A number of novel agents in various stages of development hold promise for improving therapy for patients with osteosarcoma. This article will focus on novel therapeutic approaches, including agents targeting signal-transduction pathways, inhibitors of the tumor microenvironment and immunomodulatory agents, as well as overcoming resistance mechanisms and the use of novel delivery mechanisms.

Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity--an update.

PubMed

Grunberg, Steven M; Osoba, David; Hesketh, Paul J; Gralla, Richard J; Borjeson, Sussanne; Rapoport, Bernardo L; du Bois, Andreas; Tonato, Maurizio

2005-02-01

Development of effective antiemetic therapy depends upon an understanding of both the antiemetic agents and the emetogenic challenges these agents are designed to address. New potential antiemetic agents should be studied in an orderly manner, proceeding from phase I to phase II open-label trials and then to randomized double-blind phase III trials comparing new agents and regimens to best standard therapy. Use of placebos in place of antiemetic therapy against highly or moderately emetogenic chemotherapy is unacceptable. Nausea and vomiting should be evaluated separately and for both the acute and delayed periods. Defining the emetogenicity of new antineoplastic agents is a challenge, since such data are often not reliably recorded during early drug development. A four-level classification system is proposed for emetogenicity of intravenous antineoplastic agents. A separate four-level classification system for emetogenicity of oral antineoplastic agents, which are often given over an extended period of time, is also proposed.

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.

Cats and chemotherapy: treat as 'small dogs' at your peril.

PubMed

Kent, Michael Sean

2013-05-01

To safely and effectively treat cats with cancer it is important to understand the drugs being used and some species-specific concerns in relation to chemotherapy. While many of the same principles in treating cats with chemotherapy and targeted agents hold true as for other species, including dogs, cats display altered metabolism of drugs and species-specific toxicities that can present particular challenges for veterinarians. This article is aimed at practitioners who treat feline cancer or who help manage cats undergoing cancer therapy. The article reviews the known literature regarding species differences between dogs and cats relating to the use of chemotherapy and targeted therapies. For many of the drugs mentioned there are limited studies and caution must be exercised when using drugs that have a low therapeutic index.

Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: still hope after the last hope?

PubMed

Bertocchi, Paola; Aroldi, Francesca; Prochilo, Tiziana; Meriggi, Fausto; Beretta, Giordano Domenico; Zaniboni, Alberto

2017-04-01

The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib. We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival. Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5-3.5), the median OS post-regorafenib was 2.1+ months (range 0.5-10.2) and the 6-month OS was 27.3%. Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib

In vitro Development of Chemotherapy and Targeted Therapy Drug-Resistant Cancer Cell Lines: A Practical Guide with Case Studies

PubMed Central

McDermott, Martina; Eustace, Alex J.; Busschots, Steven; Breen, Laura; Crown, John; Clynes, Martin; O’Donovan, Norma; Stordal, Britta

2014-01-01

The development of a drug-resistant cell line can take from 3 to 18 months. However, little is published on the methodology of this development process. This article will discuss key decisions to be made prior to starting resistant cell line development; the choice of parent cell line, dose of selecting agent, treatment interval, and optimizing the dose of drug for the parent cell line. Clinically relevant drug-resistant cell lines are developed by mimicking the conditions cancer patients experience during chemotherapy and cell lines display between two- and eight-fold resistance compared to their parental cell line. Doses of drug administered are low, and a pulsed treatment strategy is often used where the cells recover in drug-free media. High-level laboratory models are developed with the aim of understanding potential mechanisms of resistance to chemotherapy agents. Doses of drug are higher and escalated over time. It is common to have difficulty developing stable clinically relevant drug-resistant cell lines. A comparative selection strategy of multiple cell lines or multiple chemotherapeutic agents mitigates this risk and gives insight into which agents or type of cell line develops resistance easily. Successful selection strategies from our research are presented. Pulsed-selection produced platinum or taxane-resistant large cell lung cancer (H1299 and H460) and temozolomide-resistant melanoma (Malme-3M and HT144) cell lines. Continuous selection produced a lapatinib-resistant breast cancer cell line (HCC1954). Techniques for maintaining drug-resistant cell lines are outlined including; maintaining cells with chemotherapy, pulse treating with chemotherapy, or returning to master drug-resistant stocks. The heterogeneity of drug-resistant models produced from the same parent cell line with the same chemotherapy agent is explored with reference to P-glycoprotein. Heterogeneity in drug-resistant cell lines reflects the heterogeneity that can occur in clinical

A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

PubMed Central

Li, Fangping; Luo, Ping; Liu, Huazhong

2018-01-01

Sepia ink polysaccharide (SIP) isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami), cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents. PMID:29597272

Combination cancer chemotherapy with one compound: pluripotent bradykinin antagonists.

PubMed

Stewart, John M; Gera, Lajos; Chan, Daniel C; York, Eunice J; Simkeviciene, Vitalija; Bunn, Paul A; Taraseviciene-Stewart, Laimute

2005-08-01

Lung and prostate cancers are major health problems worldwide. Treatments with standard chemotherapy agents are relatively ineffective. Combination chemotherapy gives better treatment than a single agent because the drugs can inhibit the cancer in different pathways, but new therapeutic agents are needed for the treatment of both tumor types. Bradykinin (BK) antagonists offer advantages of combination therapy in one compound. These promising multitargeted anti-cancer compounds selectively stimulate apoptosis in cancers and also inhibit both angiogenesis and matrix metalloprotease (MMP) action in treated lung and prostate tumors in nude mice. The highly potent, metabolism-resistant bradykinin antagonist peptide dimer, B-9870 [SUIM-(DArg-Arg-Pro-Hyp-Gly-Igl-Ser-DIgl-Oic-Arg)2] (SUIM=suberimidyl; Hyp=4-hydroxyproline; Igl=alpha-(2-indanyl)glycine; Oic=octahydroindole-2-carboxylic acid) and its non-peptide mimetic, BKM-570 [2,3,4,5,6-pentafluorocinnamoyl-(o-2,6-dichlorobenzyl)-L-tyrosine-N-(4-amino-2,2,6,6-tetramethylpiperidyl)amide] are superior to the widely used but toxic chemotherapeutic drugs cisplatin and taxotere. In certain combinations, they act synergistically with standard anti-cancer drugs. Due to its structure and biological activity, BKM-570 is an attractive lead compound for derivatization and evaluation for lung and prostate cancer drugs.

[Indication of chemotherapy according to histological type of musculoskeletal sarcomas].

PubMed

Goto, Takahiro; Okuma, Tomotake; Ogura, Koichi; Imanishi, Jungo; Hozumi, Takahiro; Kondo, Taiji

2009-02-01

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. As the efficacy of chemotherapy varies according to the histological type of sarcoma, its indication is determined according to the histological type and the stage. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy, so it is absolutely necessary. Drugs commonly used for osteosarcoma include adriamycin, cisplatin, methotrexate, vincristine, and ifosfamide. For Ewing's sarcoma and rhabdomyosarcoma, vincristine, actinomycin-D, cyclophosphamide, etoposide, and ifosfamide are commonly used. On the other hand, the efficacy of chemotherapy is unclear in most of the non-round cell sarcomas, e. g., malignant fibrous histiocytoma, pleomorphic liposarcoma, and leiomyosarcoma, so adjuvant chemotherapy is relatively indicated and often performed preoperatively. The efficacy is evaluated by reduction of the tumor volume as a surrogate marker. Postoperative chemotherapy is performed when the preoperative chemotherapy is effective. Nowadays, several kinds of antitumor agents are usually used for non-round cell sarcomas, and many authors have reported various kinds of regimens and their clinical results. Among them, the key drugs are adriamycin and ifosfamide. Recently, taxanes and gemcitabine are sometimes used. For chemoresistant sarcomas, e. g., chondrosarcoma, chordoma, alveolar soft part sarcoma, chemotherapy is rarely indicated, even if the tumor is histologically high grade and large. Low-grade musculoskeletal sarcomas, e. g., low-grade chondrosarcoma, central low-grade osteosarcoma, parosteal osteosarcoma, well-differentiated liposarcoma, and dermatofibrosarcoma protuberans, are well cured only by surgical excision, and adjuvant chemotherapy is therefore not indicated. Superficially

Medication errors in chemotherapy preparation and administration: a survey conducted among oncology nurses in Turkey.

PubMed

Ulas, Arife; Silay, Kamile; Akinci, Sema; Dede, Didem Sener; Akinci, Muhammed Bulent; Sendur, Mehmet Ali Nahit; Cubukcu, Erdem; Coskun, Hasan Senol; Degirmenci, Mustafa; Utkan, Gungor; Ozdemir, Nuriye; Isikdogan, Abdurrahman; Buyukcelik, Abdullah; Inanc, Mevlude; Bilici, Ahmet; Odabasi, Hatice; Cihan, Sener; Avci, Nilufer; Yalcin, Bulent

2015-01-01

Medication errors in oncology may cause severe clinical problems due to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed to investigate unintentional medication errors and underlying factors during chemotherapy preparation and administration based on a systematic survey conducted to reflect oncology nurses experience. This study was conducted in 18 adult chemotherapy units with volunteer participation of 206 nurses. A survey developed by primary investigators and medication errors (MAEs) defined preventable errors during prescription of medication, ordering, preparation or administration. The survey consisted of 4 parts: demographic features of nurses; workload of chemotherapy units; errors and their estimated monthly number during chemotherapy preparation and administration; and evaluation of the possible factors responsible from ME. The survey was conducted by face to face interview and data analyses were performed with descriptive statistics. Chi-square or Fisher exact tests were used for a comparative analysis of categorical data. Some 83.4% of the 210 nurses reported one or more than one error during chemotherapy preparation and administration. Prescribing or ordering wrong doses by physicians (65.7%) and noncompliance with administration sequences during chemotherapy administration (50.5%) were the most common errors. The most common estimated average monthly error was not following the administration sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most important underlying reasons for medication errors were heavy workload (49.7%) and insufficient number of staff (36.5%). Our findings suggest that the probability of medication error is very high during chemotherapy preparation and administration, the most common involving prescribing and ordering errors. Further studies must address the strategies to minimize medication error in chemotherapy receiving patients, determine sufficient protective measures

Metronomic chemotherapy: A potent macerator of cancer by inducing angiogenesis suppression and antitumor immune activation.

PubMed

Biziota, Eirini; Mavroeidis, Leonidas; Hatzimichael, Eleftheria; Pappas, Periklis

2017-08-01

Metronomic chemotherapy is a low dosing treatment strategy that attracts growing scientific and clinical interest. It refers to dense and uninterrupted administration of low doses of chemotherapeutic agents (without prolonged drug free intervals) over extended periods of time. Cancer chemotherapy is conventionally given in cycles of maximum tolerated doses (MTD) with the aim of inducing maximum cancer cell apoptosis. In contrast, the primary target of metronomic chemotherapy is the tumor's neovasculature. This is relevant to the emerging concept that tumors exist in a complex microenvironment of cancer cells, stromal cells and supporting vessels. In addition to its anti-angiogenetic properties, metronomic chemotherapy halts tumor growth by activating anti-tumor immunity, thus decreasing the acquired resistance to conventional chemotherapy. Herein, we present a review of the literature that provides a scientific basis for the merits of chemotherapy when administered on a metronomic schedule. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy

PubMed Central

Jang, Hoon; Hong, Kwonho; Choi, Youngsok

2017-01-01

Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients. PMID:28590419

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. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy.

PubMed

Ghiringhelli, François; Apetoh, Lionel

2014-01-01

Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1β and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.

Olfaction in chemotherapy for head and neck malignancies.

PubMed

Haxel, Boris R; Berg, Stephanie; Boessert, Patrick; Mann, Wolf J; Fruth, Kai

2016-02-01

Systemic chemotherapy for different malignancies occurs alongside various side effects, including reduced sensory function. To date, little is known about the effect of chemotherapeutic agents on olfaction. The aim of this study was to provide new data about changes in sense of smell during chemotherapy among patients with advanced squamous cell carcinomas of the head and neck region. In a prospective, controlled cohort study of patients undergoing up to three courses of chemotherapy (cis- or carboplatin, 5-fluorouracil and docetaxel), olfaction was evaluated prior to and directly following completing a cycle, as well as 3 weeks later with the beginning of the next cycle. For evaluation of sense of smell, the established Sniffin' Sticks test with a determination of threshold, discrimination and identification (TDI) was used. Thirty-three patients (44-85 years old, 25 men and 8 women) were included in the study. Most malignancies were located in the oropharynx. Among the 28 patients who scored normosmic or hyposmic at the beginning of the study, the mean decrease in TDI-score was 0.72 points (24.0-23.2) in the first cycle, 2.1 points (24.5-22.4) in the second cycle and 0.77 points (24.2-23.4) in the third cycle. The decrease during the second cycle was significant. Age (>55 years) had a significant (negative) influence in the first and the second cycles. Smoking only showed a tendency to decreased TDI-scores in chemotherapy. In-between consecutive cycles an increase in TDI-score was obvious (+1.0 points after the first and +1.5 points after the second cycle). Chemotherapy with cisplatin, 5-fluorouracil and docetaxel significantly affected sense of smell to a small extent. This effect was more pronounced in elderly patients and smokers. This fact must be taken into account as a possible additional negative effect in usually prevailing malnutrition in these patients. Furthermore, no cumulative effect of the administered therapeutic agents on olfaction could be proven

Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.

PubMed

Wong, Jacqueline M K; Liu, Dachao; Lurain, John R

2014-01-01

To analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy. Of 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes. Twenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively. Multiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.

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.

[Home chemotherapy].

PubMed

Ichihara, Toshiaki

2010-12-01

We report the case of a male gastric cancer patient who had undergone outpatient chemotherapy with TAXOTAL+TS-1 for adrenal and lung metastases.The disease was in progress.Next, we performed home chemotherapy with TAXOL.However, this chemotherapy also was not effective either.Therefore, the patient was started on Campto with the premedication including NaseaOD, GasterD and Decadron.The 17-course was performed in the period of 12 months.However, his condition did not improve.He experienced delirium and was hospitalized and the chemotherapy was discontinued.Later, his disease was advanced further and he died.Because of our close relationship with the general hospital, this patient had undergone home chemotherapy as long as 13 months, so that if a seamless cooperation was insured, chemotherapy could have been more safely and effectively performed at the patient's home.This study suggests that home chemotherapy is an important treatment modality.

Overcoming platinum drug resistance with copper-lowering agents.

PubMed

Chen, Helen H W; Kuo, Macus Tien

2013-10-01

Platinum (Pt)-based antitumor agents have been the mainstay of cancer chemotherapy for the last three decades. While multiple mechanisms are responsible for treatment failure, deficiency in drug transport is an important contributor. The human high-affinity copper (Cu) transporter-1 (hCtr1) can also transport Pt-based drugs including cisplatin (cDDP) and carboplatin. Reduced hCtr1 expression frequently occurs in cDDP-resistant cell lines and in cancer in patients who failed chemotherapy with these drugs. We previously demonstrated that Cu chelation induces the expression of transcription factor Sp1 which binds the promoters of Sp1 and hCtr1, thereby, up-regulating their expression, whereas Cu overload shuts down hCtr1 and Sp1 expression by dissociating Sp1 from their promoter promoters. Thus, mammalian Cu homeostasis is transcriptionally regulated within a loop consisting of Sp1, hCtr1, and Cu in a three-way mutually regulated manner. These findings suggest that it is feasible to module cDDP transport capacity through intervention of mammalian Cu homeostasis. Indeed, we found that cDDP resistance can be overcome by Cu-lowering agents through enhanced hCtr1 expression by up-regulation of Sp1 in cultured cells. This discovery provided a mechanistic basis for the ongoing clinical study using Cu chelator to overcome cDDP resistance in ovarian cancer chemotherapy. Preliminary study using copper chelator (trientine) for enhancing the treatment efficacy of carboplatin in 5 ovarian cancer patients showed encouraging results. This short review describes the perspectives of using Cu-lowering agents in overcoming Pt resistance in cancer chemotherapy.

Glioma Cell Death Induced by Irradiation or Alkylating Agent Chemotherapy Is Independent of the Intrinsic Ceramide Pathway

PubMed Central

Gramatzki, Dorothee; Herrmann, Caroline; Happold, Caroline; Becker, Katrin Anne; Gulbins, Erich; Weller, Michael; Tabatabai, Ghazaleh

2013-01-01

Background/Aims Resistance to genotoxic therapy is a characteristic feature of glioma cells. Acid sphingomyelinase (ASM) hydrolyzes sphingomyelin to ceramide and glucosylceramide synthase (GCS) catalyzes ceramide metabolism. Increased ceramide levels have been suggested to enhance chemotherapy-induced death of cancer cells. Methods Microarray and clinical data for ASM and GCS in astrocytomas WHO grade II–IV were acquired from the Rembrandt database. Moreover, the glioblastoma database of the Cancer Genome Atlas network (TCGA) was used for survival data of glioblastoma patients. For in vitro studies, increases in ceramide levels were achieved either by ASM overexpression or by the GCS inhibitor DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) in human glioma cell lines. Combinations of alkylating chemotherapy or irradiation and ASM overexpression, PPMP or exogenous ceramide were applied in parental cells. The anti-glioma effects were investigated by assessing proliferation, metabolic activity, viability and clonogenicity. Finally, viability and clonogenicity were assessed in temozolomide (TMZ)-resistant cells upon treatment with PPMP, exogenous ceramide, alkylating chemotherapy, irradiation or their combinations. Results Interrogations from the Rembrandt and TCGA database showed a better survival of glioblastoma patients with low expression of ASM or GCS. ASM overexpression or PPMP treatment alone led to ceramide accumulation but did not enhance the anti-glioma activity of alkylating chemotherapy or irradiation. PPMP or exogenous ceramide induced acute cytotoxicity in glioblastoma cells. Combined treatments with chemotherapy or irradiation led to additive, but not synergistic effects. Finally, no synergy was found when TMZ-resistant cells were treated with exogenous ceramide or PPMP alone or in combination with TMZ or irradiation. Conclusion Modulation of intrinsic glioma cell ceramide levels by ASM overexpression or GCS inhibition does not

[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. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): a systematic review.

PubMed

Schloss, Janet M; Colosimo, Maree; Airey, Caroline; Masci, Paul P; Linnane, Anthony W; Vitetta, Luis

2013-12-01

Chemotherapy induced peripheral neuropathy [CIPN] is a common significant and debilitating side effect resulting from the administration of neurotoxic chemotherapeutic agents. These pharmaco-chemotherapeutics can include taxanes, vinca alkaloids and others. Moderate to severe CIPN significantly decreases the quality of life and physical abilities of cancer patients and current pharmacotherapy for CIPN e.g. Amifostine and antidepressants have had limited efficacy and may themselves induce adverse side effects. To determine the potential use of nutraceuticals i.e. vitamin E, acetyl-L-carnitine, glutamine, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as adjuvants in cancer treatments a systematic literature review was conducted. Revised clinical studies comprised of randomized clinical trials that investigated the anti-CIPN effect of nutraceuticals as the adjuvant intervention in patients administered chemotherapy. Twenty-four studies were assessed on methodological quality and limitations identified. Studies were mixed in their recommendations for nutraceuticals. Currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN. The standard of care for CIPN includes dose reduction and/or discontinuation of chemotherapy treatment. The management of CIPN remains an important challenge and future studies are warranted before recommendations for the use of supplements can be made. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

The role of chemotherapy in the treatment of malignant astrocytomas.

PubMed

Mathieu, David; Fortin, David

2006-05-01

Malignant astrocytomas are aggressive neoplasms with a dismal prognosis despite optimal treatment. Maximal resective surgery is traditionally complemented by radiation therapy. Chemotherapy is now used on patients as initial therapy when their functional status is congruent with further treatment. The classic agents used are nitrosoureas, but temozolomide has taken the front seat recently, with recent data demonstrating increased survival when this agent is used concurrently with radiation therapy in newly diagnosed glioblastoma patients. A new class of agents, refered to as biological modifiers, are increasingly used in clinical trials in an effort to affect the intrinsic biologic aberrations harboured by tumor cells. These drugs comprise differentiation agents, anti-angiogenic agents, matrix-metalloproteinase inhibitors and signal transduction inhibitors, among others. This article reviews the standard cytotoxic agents that have been used to treat malignant astrocytomas, and the different combination regimens offering promise. In addition, recent advances with biological modifiers are also discussed.

Neoadjuvant chemotherapy does not impair liver regeneration following hepatectomy or portal vein embolization for colorectal cancer liver metastases.

PubMed

Simoneau, Eve; Alanazi, Reema; Alshenaifi, Jumanah; Molla, Nouran; Aljiffry, Murad; Medkhali, Ahmad; Boucher, Louis-Martin; Asselah, Jamil; Metrakos, Peter; Hassanain, Mazen

2016-03-01

Treatment strategies for colorectal cancer liver metastasis (CRCLM) such as major hepatectomy and portal vein embolization (PVE) rely on liver regeneration. We aim to investigate the effect of neoadjuvant chemotherapy on liver regeneration occurring after PVE and after major hepatectomy. CRCLM patients undergoing PVE or major resection were identified retrospectively from our database. Liver regeneration data (expressed as future liver remnant [FLR] and percentage of liver regeneration [%LR]), total liver volume (TLV) and clinical characteristics were collected. Between 2003 and 2013, 226 patients were included (85 major resection, 141 PVE). The median chemotherapy cycles was six in both groups. The median time interval between the last chemotherapy and the intervention was 51 days in the PVE group and 79 days in the hepatectomy group. In the PVE group, chemotherapy was not associated with altered liver regeneration (number of cycles [P = 0.435], timing [P = 0.563], or chemotherapy agent [P = 0.116]). Similarly in the major hepatectomy group, preoperative chemotherapy (number of cycles [P = 0.114]; agent [P = 0.061], timing [P = 0.126]) were not significantly associated with differences in liver regeneration (P = 0.592). In both groups, the predicted FLR% was inversely correlated with the %LR (P < 0.001). Chemotherapy does not affect liver regeneration following PVE or major resection. J. Surg. Oncol. 2016;113:449-455. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A review of nabilone in the treatment of chemotherapy-induced nausea and vomiting

PubMed Central

Ware1, Mark A; Daeninck, Paul; Maida, Vincent

2008-01-01

Chemotherapy-induced nausea and vomiting (CINV) in cancer patients places a significant burden on patients’ function and quality of life, their families and caregivers, and healthcare providers. Despite the advances in preventing CINV, a substantial proportion of patients experience persistent nausea and vomiting. Nabilone, a cannabinoid, recently received Food and Drug Administration approval for the treatment of the nausea and vomiting in patients receiving cancer chemotherapy who fail to achieve adequate relief from conventional treatments. The cannabinoids exert antiemetic effects via agonism of cannabinoid receptors (CB1 and CB2). Clinical trials have demonstrated the benefits of nabilone in cancer chemotherapy patients. Use of the agent is optimized with judicious dosing and selection of patients. PMID:18728826

Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan.

PubMed

Galaup, Ariane; Paci, Angelo

2013-03-01

Among the dimethanesulfonates, busulfan, in combination with other alkylating agents or nucleoside analogues, is the cornerstone of high-dose chemotherapy. It is used, and followed hematopoietic stem cell transplantation, for the treatment of various hematologic malignancies and immunodeficiencies. Treosulfan, which is a hydrophilic analogue of busulfan, was the first dimethanesufonate registered for the treatment of ovarian cancer. Recently, treosulfan has been investigated for the treatment of hematologic malignancies in combination with the same second agents before hematopoietic stem cell transplantation. This work reviews the pharmacological data of these two dimethanesulfonates alkylating agents. Specifically, the article looks at their chemistry, metabolism, anticancer activity, and their pharmacokinetics and pharmacodynamics. Busulfan has been investigated widely for more than three decades leading to a large and precise handling of this agent with numerous studies on activity and pharmacokinetics and pharmacodynamics. In contrast, the behavior of treosulfan is still under investigation and not fully described. The complexity of treosulfan's metabolism and mechanism of action gives rise to the need of a deeper understanding of its pharmacological activity in a context of high-dose chemotherapy. Specifically, there is a great need to better understand its pharmacokinetics/pharmacodynamics relationship.

[Chemotherapy-induced peripheral neuropathies: an integrative review of the literature].

PubMed

Costa, Talita Cassanta; Lopes, Miriam; Anjos, Anna Cláudia Yokoyama Dos; Zago, Marcia Maria Fontão

2015-04-01

To identify scientific studies and to deepen the knowledge of peripheral neuropathies induced by chemotherapy antineoplastic, seeking evidence for assistance to cancer patients. Integrative review of the literature conducted in the databases Latin American and Caribbean Health Sciences (LILACS), Scientific Electronic Library Online (SciELO), Medical Literature Analysis (PubMed/MEDLINE), the Cochrane Library and the Spanish Bibliographic Index Health Sciences (IBECS). The sample consisted of 15 studies published between 2005-2014 that met the inclusion criteria. Studies showed aspects related to advanced age, main symptoms of neuropathy and chemotherapy agents as important adverse effect of neuropathy. We identified a small number of studies that addressed the topic, as well as low production of evidence related to interventions with positive results. It is considered important to develop new studies proposed for the prevention and/or treatment, enabling adjustment of the patient's cancer chemotherapy and consequently better service.

O(6)-methylguanine DNA-methyltransferase (MGMT) overexpression in melanoma cells induces resistance to nitrosoureas and temozolomide but sensitizes to mitomycin C.

PubMed

Passagne, Isabelle; Evrard, Alexandre; Depeille, Philippe; Cuq, Pierre; Cupissol, Didier; Vian, Laurence

2006-03-01

Alkylating agents play an important role in the chemotherapy of malignant melanomas. The activity of alkylating agents depends on their capacity to form alkyl adducts with DNA, in some cases causing cross-linking of DNA strands. However, the use of these agents is limited by cellular resistance induced by the DNA repair enzyme O(6)-methylguanine DNA-methyltransferase (MGMT) which removes alkyl groups from alkylated DNA strands. To determine to what extent the expression of MGMT in melanoma cells induces resistance to alkylating agents, the human cell line CAL77 Mer- (i.e., MGMT deficient) were transfected with pcMGMT vector containing human MGMT cDNA. Several clones expressing MGMT at a high level were selected to determine their sensitivity to chemotherapeutic drugs. Melanoma-transfected cells were found to be significantly less sensitive to nitrosoureas (carmustine, fotemustine, streptozotocin) and temozolomide with an increase of IC(50) values between 3 and 14 when compared to parent cells. No difference in cell survival rates between MGMT-proficient and -deficient cells was observed for melphalan, chlorambucil, busulphan, thiotepa and cisplatin which preferentially induce N(7) guanine lesions. Surprisingly, MGMT overexpression increased the sensitivity of CAL77 cells to mitomycin C by approximately 10-fold. Treatment of clonal cell lines with buthionine-[S,R]-sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase which depletes cellular glutathione, completely reversed this unexpected increase in sensitivity to mitomycin C. This observation suggests that glutathione is involved in the sensitivity of MGMT-transfected cells to mitomycin C and may act synergistically with MGMT via an unknown mechanism.

Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy.

PubMed

Montero, Joan; Sarosiek, Kristopher A; DeAngelo, Joseph D; Maertens, Ophélia; Ryan, Jeremy; Ercan, Dalia; Piao, Huiying; Horowitz, Neil S; Berkowitz, Ross S; Matulonis, Ursula; Jänne, Pasi A; Amrein, Philip C; Cichowski, Karen; Drapkin, Ronny; Letai, Anthony

2015-02-26

There is a lack of effective predictive biomarkers to precisely assign optimal therapy to cancer patients. While most efforts are directed at inferring drug response phenotype based on genotype, there is very focused and useful phenotypic information to be gained from directly perturbing the patient's living cancer cell with the drug(s) in question. To satisfy this unmet need, we developed the Dynamic BH3 Profiling technique to measure early changes in net pro-apoptotic signaling at the mitochondrion ("priming") induced by chemotherapeutic agents in cancer cells, not requiring prolonged ex vivo culture. We find in cell line and clinical experiments that early drug-induced death signaling measured by Dynamic BH3 Profiling predicts chemotherapy response across many cancer types and many agents, including combinations of chemotherapies. We propose that Dynamic BH3 Profiling can be used as a broadly applicable predictive biomarker to predict cytotoxic response of cancers to chemotherapeutics in vivo. Copyright © 2015 Elsevier Inc. All rights reserved.

Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy.

PubMed

Houédé, N; Locker, G; Lucas, C; Parra, H Soto; Basso, U; Spaeth, D; Tambaro, R; Basterretxea, L; Morelli, F; Theodore, C; Lusuardi, L; Lainez, N; Guillot, A; Tonini, G; Bielle, J; Del Muro, X Garcia

2016-09-23

Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia < 10 g/dL in 16 %, hepatic metastases in 13 %. 80 % of these patients received further anticancer therapy. Immediately after failure of adjuvant/neoadjuvant chemotherapy, most subsequent anticancer treatments were chemotherapy doublets (35/58), whereas after therapy failure in the advanced setting most patients receiving further anticancer drugs were treated with a single agent (80/114). After first progression to chemotherapy, treatment decisions were mainly driven by Performance Status and prior response to chemotherapy (>30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. In this daily practice experience, a majority of patients with urothelial carcinoma previously treated

Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.

PubMed

Shamsi, Milad; Sedaghatkish, Amir; Dejam, Morteza; Saghafian, Mohsen; Mohammadi, Mehdi; Sanati-Nezhad, Amir

2018-11-01

Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors

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

The development of bis(hydroxymethyl)pyrrole analogs as bifunctional DNA cross-linking agents and their chemotherapeutic potential.

PubMed

Su, Tsann-Long; Lee, Te-Chang; Kakadiya, Rajesh

2013-11-01

Bifunctional DNA cross-linking agents are widely used as chemotherapeutic agents in clinics. The advance in the development of these agents as potential antitumor agents has generated various types of bis(hydroxymethyl)pyrrole analogs. In order to develop highly effective anticancer agents, it is necessary to understand the chemophysical properties, structure-activity relationships, therapeutic potency, toxicity/safety, and pharmacokinetics of these DNA cross-linking agents. This review presents an overview of the recent advances in developing various types of bis(hydroxymethyl)pyrrole analogs with potential antitumor activity to provide more information for future drug design and strategies for combination chemotherapy. The rational drug design, chemical syntheses, antitumor activity, mechanism of action, and development of combined chemotherapy regimens, including a DNA repair inhibitor, are discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Resistance to antitumor chemotherapy due to bounded-noise-induced transitions

NASA Astrophysics Data System (ADS)

D'Onofrio, Alberto; Gandolfi, Alberto

2010-12-01

Tumor angiogenesis is a landmark of solid tumor development, but it is also directly relevant to chemotherapy. Indeed, the density and quality of neovessels may influence the effectiveness of therapies based on blood-born agents. In this paper, first we define a deterministic model of antiproliferative chemotherapy in which the drug efficacy is a unimodal function of vessel density, and then we show that under constant continuous infusion therapy the tumor-vessel system may be multistable. However, the actual drug concentration profiles are affected by bounded even if possibly large fluctuations. Through numerical simulations, we show that the tumor volume may undergo transitions to the higher equilibrium value induced by the bounded noise. In case of periodically delivered boli-based chemotherapy, we model the fluctuations due to time variability of both the drug clearance rate and the distribution volume, as well as those due to irregularities in drug delivery. We observed noise-induced transitions also in case of periodic delivering. By applying a time dense scheduling with constant average delivered drug (metronomic scheduling), we observed an easier suppression of the transitions. Finally, we propose to interpret the above phenomena as an unexpected non-genetic kind of resistance to chemotherapy.

[In vitro indirect pathogenesis of Pseudomonas aeruginosa against anti MRSA chemotherapy].

PubMed

Satoh, Naotake; Kondo, Shigemi; Yamada, Toshihiko; Saionji, Katsu; Oguri, Toyoko; Igari, Jun

2004-09-01

In the patient with a chronic respiratory disease, both Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) are frequently detected from expectoration. Vancomycin (VCM) and arbekacin (ABK) are both recommended for the chemotherapy of MRSA infection in Japan. Minocycline (MINO) is also selected for the treatment of MRSA infection. While rifampicin (RFP) and a trimetoprim-sulfamethoxazole combination (ST) are also recommended in Europe and USA but not recommended in Japan for the chemotherapy of MRSA infection. It is pointed out that coexistence bacteria affect chemotherapy as an indirect pathogen. Not only an antibacterial action but the immunological action or the metabolic effect against chronic P. aeruginosa infection such as DPB is known by the administration of 14-membered ring macrolides including erythromycin (EM). We considered the influence of P. aeruginosa isolated with MRSA on the activity against anti-MRSA agents by the disk diffusion method with bilayer flat agar in vitro. Moreover, we also examined the influence of EM against the activity of the anti-MRSA agents when P. aeruginosa was coexistence. One strain of MRSA as an indicator strain and 100 strains of P. aeruginosa as test strains, which were obtained from clinical materials, were used for the following experiment. P. aeruginosa was streaked on to the Mueller-Hinton agar culture medium (MHA), and they incubated at 35 degrees C for 24 hours. Then, the blood agar plate was piled up, MRSA was streaked on the blood agar surface, the susceptibility test disks (VCM, ABK, MINO, RFP, ST) were put on it, and incubated at 35 degrees C for a further 24 hours. The diameter of the zone of inhibition around the susceptibility disks against MRSA was measured and compared with P. aeruginosa free experiments. The anti-MRSA activity of MINO, ST and ABK was reduced by coexistence of P. aeruginosa. In RFP and VCM, the anti-MRSA activity was reinforced by coexistence of P. aeruginosa

Chemotherapy- and radiotherapy-induced oral mucositis: review of preventive strategies and treatment.

PubMed

Saadeh, Claire E

2005-04-01

Oral mucositis is a frequently encountered and potentially severe complication associated with administration of chemotherapy and radiotherapy. Although many pharmacologic interventions have been used for the prevention and treatment of oral mucositis, there is not one universally accepted strategy for its management. Most preventive and treatment strategies are based on limited, often anecdotal, clinical data. Basic oral hygiene and comprehensive patient education are important components of care for any patient with cancer at risk for development of oral mucositis. Nonpharmacologic approaches for the prevention of oral mucositis include oral cryotherapy for patients receiving chemotherapy with bolus 5-fluorouracil, and low-level laser therapy for patients undergoing hematopoietic stem cell transplantation. Chlorhexidine, amifostine, hematologic growth factors, pentoxifylline, glutamine, and several other agents have all been investigated for prevention of oral mucositis. Results have been conflicting, inconclusive, or of limited benefit. Treatment of established mucositis remains a challenge and focuses on a palliative management approach. Topical anesthetics, mixtures (also called cocktails), and mucosal coating agents have been used despite the lack of experimental evidence supporting their efficacy. Investigational agents are targeting the specific mechanisms of mucosal injury; among the most promising of these is recombinant human keratinocyte growth factor.

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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A systematic review of utility values for chemotherapy-related adverse events.

PubMed

Shabaruddin, Fatiha H; Chen, Li-Chia; Elliott, Rachel A; Payne, Katherine

2013-04-01

Chemotherapy offers cancer patients the potential benefits of improved mortality and morbidity but may cause detrimental outcomes due to adverse drug events (ADEs), some of which requiring time-consuming, resource-intensive and costly clinical management. To appropriately assess chemotherapy agents in an economic evaluation, ADE-related parameters such as the incidence, (dis)utility and cost of ADEs should be reflected within the model parameters. To date, there has been no systematic summary of the existing literature that quantifies the utilities of ADEs due to healthcare interventions in general and chemotherapy treatments in particular. This review aimed to summarize the current evidence base of reported utility values for chemotherapy-related ADEs. A structured electronic search combining terms for utility, utility valuation methods and generic terms for cancer treatment was conducted in MEDLINE and EMBASE in June 2011. Inclusion criteria were: (1) elicitation of utility values for chemotherapy-related ADEs and (2) primary data. Two reviewers identified studies and extracted data independently. Any disagreements were resolved by a third reviewer. Eighteen studies met the inclusion criteria from the 853 abstracts initially identified, collectively reporting 218 utility values for chemotherapy-related ADEs. All 18 studies used short descriptions (vignettes) to obtain the utility values, with nine studies presenting the vignettes used in the valuation exercises. Of the 218 utility values, 178 were elicited using standard gamble (SG) or time trade-off (TTO) approaches, while 40 were elicited using visual analogue scales (VAS). There were 169 utility values of specific chemotherapy-related ADEs (with the top ten being anaemia [34 values], nausea and/or vomiting [32 values], neuropathy [21 values], neutropenia [12 values], diarrhoea [12 values], stomatitis [10 values], fatigue [8 values], alopecia [7 values], hand-foot syndrome [5 values] and skin reaction [5 values

Development of a Mouse Model for Assessing Fatigue during Chemotherapy

PubMed Central

Ray, Maria A; Trammell, Rita A; Verhulst, Steve; Ran, Sophia; Toth, Linda A

2011-01-01

Fatigue and disturbed sleep are common problems for cancer patients and affect both quality of life and compliance with treatment. Fatigue may be associated with cancer itself and with the treatment, particularly for therapies with neurotoxic side effects. To develop a model system for evaluation of chemotherapy-related fatigue, we studied mice treated with either a commonly used formulation of the chemotherapeutic agent paclitaxel (paclitaxel; Taxol), which is known to have neurotoxic properties, or a nanoparticle formulation of paclitaxel (nab-paclitaxel; Abraxane) that is reported to have greater potency and efficacy yet fewer side effects than does paclitaxel. Mice were treated with 1 of these 2 agents (10 mg/kg IV daily for 5 consecutive days) and were monitored from 1 wk before through 4 wk after treatment. Dependent measures included running wheel activity, locomotor activity on the cage floor, core temperature, sleep patterns, CBC count, serum cytokine and chemokine concentrations, and neurologic assessment. For both drugs, mice showed the most severe perturbations of activity during the first recovery week after drug administration. Mice treated with paclitaxel showed greater neutropenia and motor deficits than did mice treated with nab-paclitaxel. However, deficits had largely resolved by 4 wk after administration of either drug. We conclude that these measures provide an assessment of chemotherapy-related fatigue that potentially can distinguish toxicity associated with different formulations of the same agent. PMID:21535922

[Antitubercular agents].

PubMed

Gartmann, J

1999-12-01

The personally experienced development of chemotherapy for tuberculosis during the last half century represents some highlights of new knowledges and practical successes: the discovery of antituberculosis drugs; the comprehension of their actions and side effects; the exploration of mechanisms of resistance against antituberculosis agents; the evaluation of therapeutic and epidemiologic consequences of resistant strains; the decoding of the mycobacterial genetic structure. For different economic, social and psychologic reasons, the worldwide results of the battle against tuberculosis are not nearly as good as possible. AIDS is only a partial factor of this failure.

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

PubMed

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Rational drug design for anti-cancer chemotherapy: multi-target QSAR models for the in silico discovery of anti-colorectal cancer agents.

PubMed

Speck-Planche, Alejandro; Kleandrova, Valeria V; Luan, Feng; Cordeiro, M Natália D S

2012-08-01

The discovery of new and more potent anti-cancer agents constitutes one of the most active fields of research in chemotherapy. Colorectal cancer (CRC) is one of the most studied cancers because of its high prevalence and number of deaths. In the current pharmaceutical design of more efficient anti-CRC drugs, the use of methodologies based on Chemoinformatics has played a decisive role, including Quantitative-Structure-Activity Relationship (QSAR) techniques. However, until now, there is no methodology able to predict anti-CRC activity of compounds against more than one CRC cell line, which should constitute the principal goal. In an attempt to overcome this problem we develop here the first multi-target (mt) approach for the virtual screening and rational in silico discovery of anti-CRC agents against ten cell lines. Here, two mt-QSAR classification models were constructed using a large and heterogeneous database of compounds. The first model was based on linear discriminant analysis (mt-QSAR-LDA) employing fragment-based descriptors while the second model was obtained using artificial neural networks (mt-QSAR-ANN) with global 2D descriptors. Both models correctly classified more than 90% of active and inactive compounds in training and prediction sets. Some fragments were extracted from the molecules and their contributions to anti-CRC activity were calculated using mt-QSAR-LDA model. Several fragments were identified as potential substructural features responsible for the anti-CRC activity and new molecules designed from those fragments with positive contributions were suggested and correctly predicted by the two models as possible potent and versatile anti-CRC agents. Copyright © 2012 Elsevier Ltd. All rights reserved.

Water-soluble polymer–drug conjugates for combination chemotherapy against visceral leishmaniasis

PubMed Central

Nicoletti, Salvatore; Seifert, Karin; Gilbert, Ian H.

2010-01-01

There is a need for new safe, effective and short-course treatments for leishmaniasis; one strategy is to use combination chemotherapy. Polymer–drug conjugates have shown promise for the delivery of anti-leishmanial agents such as amphotericin B. In this paper, we report on the preparation and biological evaluation of polymer–drug conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA), amphotericin B and alendronic acid. The combinatorial polymer–drug conjugates were effective anti-leishmanial agents in vitro and in vivo, but offered no advantage over the single poly(HPMA)–amphotericin B conjugates. PMID:20338769

A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer

PubMed Central

Huang, Chih-Yang; Ju, Da-Tong; Chang, Chih-Fen; Muralidhar Reddy, P.; Velmurugan, Bharath Kumar

2017-01-01

Lung cancer is the leading cause of cancer deaths worldwide, and this makes it an attractive disease to review and possibly improve therapeutic treatment options. Surgery, radiation, chemotherapy, targeted treatments, and immunotherapy separate or in combination are commonly used to treat lung cancer. However, these treatment types may cause different side effects, and chemotherapy-based regimens appear to have reached a therapeutic plateau. Hence, effective, better-tolerated treatments are needed to address and hopefully overcome this conundrum. Recent advances have enabled biologists to better investigate the potential use of natural compounds for the treatment or control of various cancerous diseases. For the past 30 years, natural compounds have been the pillar of chemotherapy. However, only a few compounds have been tested in cancerous patients and only partial evidence is available regarding their clinical effectiveness. Herein, we review the research on using current chemotherapy drugs and natural compounds (Wortmannin and Roscovitine, Cordyceps militaris, Resveratrol, OSU03013, Myricetin, Berberine, Antroquinonol) and the beneficial effects they have on various types of cancers including non-small cell lung cancer. Based on this literature review, we propose the use of these compounds along with chemotherapy drugs in patients with advanced and/or refractory solid tumours. PMID:29130448

Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort

PubMed Central

Shah, Arya; Hoffman, E. Matthew; Mauermann, Michelle L; Loprinzi, Charles L; Windebank, Anthony J; Klein, Christopher J; Staff, Nathan P

2018-01-01

OBJECTIVE To assess disease burden of chemotherapy-induced peripheral neuropathy (CIPN), which is a common dose-limiting side-effect of neurotoxic chemotherapy. Late effects of CIPN may increase with improved cancer survival. METHODS Olmsted County, Minnesota residents receiving neurotoxic chemotherapy were identified and CIPN was ascertained via text searches of polyneuropathy symptoms in the medical record. Clinical records were queried to collect data on baseline characteristics, risk factors, signs and symptoms of CIPN, medications, impairments, and ICD-9 diagnostic codes for all subjects. RESULTS A total of 509 individuals with incident exposure to an inclusive list of neurotoxic chemotherapy agents between 2006 and 2008 were identified. 268 (52.7%) of these individuals were determined to have CIPN. The median time from incident exposure to first documented symptoms was 71 days. Patients with CIPN received a neuropathy ICD-9 diagnosis in only 37 instances (13.8%). Pain symptoms and use of pain medications were observed more often in patients with CIPN. 5-year survival was greater in those with CIPN (55.2%) versus those without (36.1%). Those with CIPN surviving greater than 5 years (n=145) continued to have substantial impairments and were more likely to be prescribed opioids than those without CIPN (OR 2.0, 1.06–3.69). CONCLUSIONS Results from our population-based study are consistent with previous reports of high incidence of CIPN in the first two years following incident exposure to neurotoxic chemotherapeutic agents, and its association with significant pain symptomatology and accompanied long-term opioid use. Increased survival following exposure to neurotoxic chemotherapy and its long-term disease burden necessitates further study of among survivors. PMID:29439162

Using Epigenetic Therapy to Overcome Chemotherapy Resistance.

PubMed

Strauss, Julius; Figg, William D

2016-01-01

It has been known for decades that as cancer progresses, tumors develop genetic alterations, making them highly prone to developing resistance to therapies. Classically, it has been thought that these acquired genetic changes are fixed. This has led to the paradigm of moving from one cancer therapy to the next while avoiding past therapies. However, emerging data on epigenetic changes during tumor progression and use of epigenetic therapies have shown that epigenetic modifications leading to chemotherapy resistance have the potential to be reversible with epigenetic therapy. In fact, promising clinical data exist that treatment with epigenetic agents can diminish chemotherapy resistance in a number of tumor types including chronic myelogenous leukemia, colorectal, ovarian, lung and breast cancer. The potential for epigenetic-modifying drugs to allow for treatment of resistant disease is exciting and clinical trials have just begun to evaluate this area. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Effect of YH0618 soup on chemotherapy-induced toxicity in patients with cancer who have completed chemotherapy: study protocol for a randomized controlled trial.

PubMed

You, Jie-Shu; Chen, Jian-Ping; Chan, Jessie S M; Lee, Ho-Fun; Wong, Mei-Kuen; Yeung, Wing-Fai; Lao, Li-Xing

2016-07-26

The incidence of cancer has been staying at a high level worldwide in recent years. With advances in cancer diagnosis and therapy strategy, the survival rate of patients with cancer has been increasing, but the side effects of these treatments, especially chemotherapy, are obvious even when the chemotherapy ceases. YH0618, a prescription, has showed efficacy in reducing chemotherapy-induced toxicity through long clinical practice. However, there is no scientific research exploring the effects of YH0618 in patients with cancer. Therefore, using a randomized controlled trial, this study will explore the efficacy of YH0618 on ameliorating chemotherapy-induced toxicity including dermatologic toxicity, myelosuppression, hepatotoxicity and nephrotoxicity and improving fatigue in cancer patients who have completed chemotherapy. This is a prospective assessor-blinded, parallel, randomized controlled trial. Patients with cancer at any stage who have completed chemotherapy within two weeks will be randomly divided into group A (YH0618) and group B (wait-list) using a 1:1 allocation ratio. The chemotherapeutic agents include taxanes or anthracyclines. Subjects assigned to group A will receive YH0618 soup 6 days a week for 6 weeks and uncontrolled follow-up for 6 weeks, while group B are required to wait for 6 weeks before receiving YH0618 intervention. The primary outcome of this study is the incidence of protocol-specified grade ≥2 dermatologic toxicities graded by NCI CTCAE Chinese version 4.0 and changes of fingernail color, face skin color and tongue color evaluated by the L*a*b system within 6 weeks. There are some secondary outcomes associated with dermatologic toxicity including fatigue and clinical objective examination. There are few scientific and safe methods in ameliorating chemotherapy-induced toxicity. The proposed study may provide direct and convincing evidence to support YH0618 as an adjuvant treatment for reducing chemotherapy-induced toxicity, which

A novel and selective poly (ADP-ribose) polymerase inhibitor ameliorates chemotherapy-induced painful neuropathy.

PubMed

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

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. 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. 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.

Risk factors for febrile neutropenia during chemotherapy for HIV-related lymphoma.

PubMed

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Park, Wan Beom; Oh, Myoung-don

2012-12-01

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma.

Effect of PUFAs Oral Administration on the Amount of Apoptotic Caspases Enzymes in Gastric Cancer Patients Undergoing Chemotherapy.

PubMed

Dolatkhah, Homayun; Movahedian, Ahmad; Somi, Mohammad-Hossein; Aghaei, Mahmud; Samadi, Naser; Mirza-Aghazade, Ahmad; Esfahani, Ali

2017-01-01

Gastric cancer is the fourth most common cancer and the second cause of death in the world. According to the studies, the gastric cancer is relatively sensitive to chemotherapy. The aim of this study was to investigate the association of oral administer PUFAs with Caspase enzymes in patients with gastric cancer under chemotherapy. This study was a Clinical Trial in which the target group consisted of the patients recognized with gastric cancer for the first time and cured under chemotherapy. Thirty-four patients were selected and categorized randomly into two groups. The case group included the patients taking PUFAs along with chemotherapeutic agent. In these patients, chemotherapy started with Cis-Platin plus PUFAs supplement in the scale of 3600 mg daily and in three courses. In control group, the individuals were under the same chemotherapy protocol without PUFAs. Biopsy samples from tumor were taken from the patients before and after chemotherapy. Levels of mRNA and protein expression of caspase 3, 8, 9 were measured in biopsy samples by Real-Time PCR and Frozen Section methods. The levels of apoptosis were determined using DNA-damage colorimetric assay. In the case group, caspase 3 showed a significant increase in both gene and protein expression levels after administration of PUFAs supplement in comparison with those of the control group (p=0.006 for gene, p=0.001 for protein). PUFAs induced caspase-9 gene expression level in these patients (p<0.0001). Caspase-9 protein level also revealed a marked elevation when PUFAs were administered along with chemotherapeutic agent (p<0.0001). DNA damage in gastric tissue from the patients under PUFAs treatment plus Cis-Platin was significantly higher than that of control group (p=0.003). PUFAs showed no significant changes in caspase-8 both at the gene and protein levels in the patients. According to the results of present study, it appears that oral administration of PUFAs can elevate the efficacy of chemotherapy agent

Role of ABCB5 P-Glycoprotein in Breast Cancer Multidrug Resistance

DTIC Science & Technology

2005-09-01

Hydroxyurea Doxorubicin Porfiromycin Mechlorethamine Fluorodopan Mitomycin Cytarabine (araC) Dianhydrogalactitol Gemcitabine Thiotepa N-N-Dibenzyl-daunomycin...0.0196 Mitomycin 0.4173 0.0318 Cytarabine (araC) 0.4163 0.0288 Dianhydrogalactitol 0.4105 0.0354 Gemcitabine 0.4088 0.0302 Thiotepa 0.4015 0.0232

Alterations of nutritional status: impact of chemotherapy and radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donaldson, S.S.; Lenon, R.A.

1979-05-01

The nutritional status of a cancer patient may be affected by the tumor, the chemotherapy and/or radiation therapy directed against the tumor, and by complications associated with that therapy. Chemotherpay-radiotherapy is not confined exclusively to malignant cell populations; thus, normal tissues may also be affected by the therapy and may contribute to specific nutritional problems. Impaired nutrition due to anorexia, mucositis, nausea, vomiting, and diarrhea may be dependent upon the specific chemotherapeutic agent, dose, or schedule utilized. Similar side effects from radiation therapy depend upon the dose, fractionation, and volume irradiated. When combined modality treatment is given the nutritional consequencesmore » may be magnified. Prospective, randomized clinical trials are underway to investigate the efficacy of nutritional support during chemotherapy-radiotherapy on tolerance to treatment, complications from treatment, and response rates to treatment. Preliminary results demonstrate that the administration of total parenteral nutrition is successful in maintaining weight during radiation therapy and chemotherapy, but that weight loss occurs after discontinuation of nutritional support. Thus, longterm evaluation is mandatory to learn the impact of nutritional support on survival, diease-free survival, and complication rates, as well as on the possible prevention of morbidity associated with aggressive chemotherapy-radiation therapy.« less

[Pneumocystis Pneumonia during Adjuvant Chemotherapy for Advanced Colon Cancer - A Case Report].

PubMed

Fujiwara, Yushi; Lee, Shigeru; Kishida, Satoru; Hashiba, Ryoya; Gyobu, Ken; Osugi, Harushi

2015-11-01

We report a case of pneumocystis pneumonia (PCP) during adjuvant chemotherapy for advanced sigmoid colon cancer. A 70-year-old Japanese man was referred to our hospital after complaining of bloody stools. He was diagnosed with advanced sigmoid colon cancer, T2N2aM1b, Stage IV B. After 3 cycles of mFOLFOX6 plus panitumumab as first-line chemotherapy, he received FOLFIRI plus bevacizumab as second-line chemotherapy because of progressive disease. Aprepitant and steroids were administered as antiemetic agents for a short period during each chemotherapy session. During the 2 cycle of FOLFIRI plus bevacizumab, he developed a high fever without respiratory symptoms. Chest CT revealed ground-glass opacities in both the lungs. We first treated him with antibiotics (PIPC/TAZ plus GRNX), suspecting bacterial pneumonia. However, based on the elevation of serum b -D-glucan (148 pg/mL), we diagnosed PCP and initiated SMX/TMP in addition to PIPC/TAZ. The inflammation promptly decreased, and follow-up chest CT revealed the disappearance of the ground-glass opacities. If a patient develops a fever or respiratory symptoms during a course of chemotherapy, we should consider the possibility of PCP and perform careful examinations.

Interscience Conference on Antimicrobial Agents and Chemotherapy--49th annual meeting. Part 1. 11-15 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 a beta-cyclodextrin derivative for the treatment of Staphylococcus aureus infections, a type 3 secretion system inhibitor for the treatment of Pseudomonas aeruginosa infections, a small-molecule inhibitor of the fungal Hos2 HDAC, a TLR9 agonist used as an adjuvant, a CMV vaccine, a glycopeptide-cephalosporin heterodimer antibiotic, a topical quinolone for the treatment of complicated skin and skin structure infections, a broad-spectrum glycylcycline antibiotic and an HCV RNA replication inhibitor. Investigational drugs discussed include IB-201 (Innovative Biologics Inc), MBX-1641 (Microbiotix Inc), MGCD-290 (MethylGene Inc), agatolimod (Coley Pharmaceutical Group Inc/Pfizer Inc/GlaxoSmithKline plc/Merck & Co Inc/Dynavax Technologies Corp/Novartis AG/Emergent BioSolutions Inc), TD-1792 (Theravance Inc), ozenoxacin (Ferrer Internacional SA/Maruho Co Ltd/Toyama Chemical Co Ltd) and ATI-0810 (Arisyn Therapeutics Inc).

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

Procoagulant effects of lung cancer chemotherapy: impact on microparticles and cell-free DNA.

PubMed

Lysov, Zakhar; Dwivedi, Dhruva J; Gould, Travis J; Liaw, Patricia C

2017-01-01

Lung cancer is the second leading type of cancer, with venous thromboembolism being the second leading cause of death. Studies have shown increased levels of microparticles and cell-free DNA (CFDNA) in cancer patients, which can activate coagulation through extrinsic and intrinsic pathways, respectively. However, the impact of lung cancer chemotherapy on microparticle and/or CFDNA generation is not completely understood. The aim of the study was to study the effects of platinum-based chemotherapeutic agents on generation of procoagulant microparticles and CFDNA in vitro and in vivo. Microparticles were isolated from chemotherapy-treated monocytes, human umbilical vein endothelial cells, or cancer cells. Tissue factor (TF) and phosphatidylserine levels were characterized and thrombin/factor Xa generation assays were used to determine microparticle procoagulant activity. CFDNA levels were isolated from cell supernatants and plasma. A murine xenograft model of human lung carcinoma was used to study the procoagulant effects of TF microparticles and CFDNA in vivo. In vitro, platinum-based chemotherapy induced TF/phosphatidylserine microparticle shedding from A549 and A427 lung cancers cells, which enhanced thrombin generation in plasma in a FVII-dependent manner. CFDNA levels were increased in supernatants of chemotherapy-treated neutrophils and plasma of chemotherapy-treated mice. TF microparticles were elevated in plasma of chemotherapy-treated tumour-bearing mice. Plasma CFDNA levels are increased in chemotherapy-treated tumour-free mice and correlate with increased thrombin generation. In tumour-bearing mice, chemotherapy increases plasma levels of CFDNA and TF/phosphatidylserine microparticles. Platinum-based chemotherapy induces the shedding of TF/phosphatidylserine microparticles from tumour cells and the release of CFDNA from host neutrophils.

On the MTD paradigm and optimal control for multi-drug cancer chemotherapy.

PubMed

Ledzewicz, Urszula; Schättler, Heinz; Gahrooi, Mostafa Reisi; Dehkordi, Siamak Mahmoudian

2013-06-01

In standard chemotherapy protocols, drugs are given at maximum tolerated doses (MTD) with rest periods in between. In this paper, we briey discuss the rationale behind this therapy approach and, using as example multidrug cancer chemotherapy with a cytotoxic and cytostatic agent, show that these types of protocols are optimal in the sense of minimizing a weighted average of the number of tumor cells (taken both at the end of therapy and at intermediate times) and the total dose given if it is assumed that the tumor consists of a homogeneous population of chemotherapeutically sensitive cells. A 2-compartment linear model is used to model the pharmacokinetic equations for the drugs.

Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

PubMed

Craig, Morgan; Humphries, Antony R; Nekka, Fahima; Bélair, Jacques; Li, Jun; Mackey, Michael C

2015-11-21

The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Types of chemotherapy

MedlinePlus

... or on cancer cells. How Doctors Choose Your Chemotherapy The type and dose of chemotherapy your doctor gives you ... drugs. Below are the seven main types of chemotherapy, the types of cancer they treat, and examples. The caution ...

Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer: Clinical, Neurophysiological, Functional, and Patient-Reported Outcomes.

PubMed

Kandula, Tejaswi; Farrar, Michelle Anne; Cohn, Richard J; Mizrahi, David; Carey, Kate; Johnston, Karen; Kiernan, Matthew C; Krishnan, Arun V; Park, Susanna B

2018-05-14

In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors. To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations. In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation. Chemotherapy agents known to be toxic to peripheral nerves. The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures. Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 54 of 107 participants (50.5%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 μV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient

Technical considerations in the preparation and dispensing of chemotherapy.

PubMed

Peters, B G

1995-01-01

The safe handling of cytotoxic agents is intimately related to the technical aspects of drug preparation, dispensing, and administration. The appropriate equipment, supplies, protective clothing, and waste disposal systems must be available to the health care worker who is called upon to prepare cytotoxic agents. In addition, the health care worker must be adequately trained in and familiar with the safe use of these products and equipment and the preparation techniques or manipulations necessary during cytotoxic drug compounding. The article describes in detail and reviews the technical considerations, such as aseptic technique, proper use of the biological safety cabinet, gowning and gloving, labeling, and waste disposal, that are essential to the safe preparation and dispensing of chemotherapy.

[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.

Extraordinary response of metastatic pancreatic cancer to apatinib after failed chemotherapy: A case report and literature review.

PubMed

Li, Cheng-Ming; Liu, Zhi-Chao; Bao, You-Ting; Sun, Xin-Dong; Wang, Lin-Lin

2017-11-07

Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer (PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage IV, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well.

Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort.

PubMed

Shah, Arya; Hoffman, E Matthew; Mauermann, Michelle L; Loprinzi, Charles L; Windebank, Anthony J; Klein, Christopher J; Staff, Nathan P

2018-06-01

To assess disease burden of chemotherapy-induced peripheral neuropathy (CIPN), which is a common dose-limiting side effect of neurotoxic chemotherapy. Late effects of CIPN may increase with improved cancer survival. Olmsted County, Minnesota residents receiving neurotoxic chemotherapy were identified and CIPN was ascertained via text searches of polyneuropathy symptoms in the medical record. Clinical records were queried to collect data on baseline characteristics, risk factors, signs and symptoms of CIPN, medications, impairments and International Classification of Diseases, Ninth Revision (ICD-9) diagnostic codes for all subjects. A total of 509 individuals with incident exposure to an inclusive list of neurotoxic chemotherapy agents between 2006 and 2008 were identified. 268 (52.7%) of these individuals were determined to have CIPN. The median time from incident exposure to first documented symptoms was 71 days. Patients with CIPN received a neuropathy ICD-9 diagnosis in only 37 instances (13.8%). Pain symptoms and use of pain medications were observed more often in patients with CIPN. Five-year survival was greater in those with CIPN (55.2%) versus those without (36.1%). Those with CIPN surviving greater than 5 years (n=145) continued to have substantial impairments and were more likely to be prescribed opioids than those without CIPN (OR 2.0, 1.06-3.69). Results from our population-based study are consistent with previous reports of high incidence of CIPN in the first 2 years following incident exposure to neurotoxic chemotherapeutic agents, and its association with significant pain symptomatology and accompanied long-term opioid use. Increased survival following exposure to neurotoxic chemotherapy and its long-term disease burden necessitates further study among survivors. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy

PubMed Central

Navari, Rudolph M

2009-01-01

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 (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. This review provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Palonosetron has a longer half-life and a higher binding affinity than the first-generation 5-HT3 receptor antagonists. Palonosetron 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 to the first-generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials which were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due 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. PMID:21188135

A Case of Neurotoxicity Following 5-Fluorouracil-based Chemotherapy

PubMed Central

Ki, Seung Seog; Jeong, Jin Mo; Kim, Seong Ho; Jeong, Sook Hyang; Lee, Jin Hyuk; Han, Chul Ju; Kim, You Cheol; Lee, Jhin Oh; Hong, Young Joon

2002-01-01

5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent. However, its neurotoxicity is rare and not well recognized. We report a case of 5-FU neurotoxicity with organic brain syndrome and progression to multifocal leukoencephalopathy in a 44-year-old male patient having malignant gastrointestinal stromal tumor. 5-FU-induced neurotoxicity should, therefore, be considered as an important differential diagnosis in cancer patients with neurological abnormality and history of chemotherapy. PMID:12014219

Targeting HSP70 and GRP78 in canine osteosarcoma cells in combination with doxorubicin chemotherapy.

PubMed

Asling, Jonathan; Morrison, Jodi; Mutsaers, Anthony J

2016-11-01

Heat shock proteins (HSPs) are molecular chaperones subdivided into several families based on their molecular weight. Due to their cytoprotective roles, these proteins may help protect cancer cells against chemotherapy-induced cell death. Investigation into the biologic activity of HSPs in a variety of cancers including primary bone tumors, such as osteosarcoma (OSA), is of great interest. Both human and canine OSA tumor samples have aberrant production of HSP70. This study assessed the response of canine OSA cells to inhibition of HSP70 and GRP78 by the ATP-mimetic VER-155008 and whether this treatment strategy could sensitize cells to doxorubicin chemotherapy. Single-agent VER-155008 treatment decreased cellular viability and clonogenic survival and increased apoptosis in canine OSA cell lines. However, combination schedules with doxorubicin after pretreatment with VER-155008 did not improve inhibition of cellular viability, apoptosis, or clonogenic survival. Treatment with VER-155008 prior to chemotherapy resulted in an upregulation of target proteins HSP70 and GRP78 in addition to the co-chaperone proteins Herp, C/EBP homologous transcription protein (CHOP), and BAG-1. The increased GRP78 was more cytoplasmic in location compared to untreated cells. Single-agent treatment also revealed a dose-dependent reduction in activated and total Akt. Based on these results, targeting GRP78 and HSP70 may have biologic activity in canine osteosarcoma. Further studies are required to determine if and how this strategy may impact the response of osteosarcoma cells to chemotherapy.

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

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

Systemic use of tumor necrosis factor alpha as an anticancer agent

PubMed Central

Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

[Recent advance in chemotherapy for advanced colorectal cancer].

PubMed

Aiba, K

1996-04-01

Chemotherapy for advanced colorectal cancer is reviewed stressing the historical development of combination chemotherapy and the application of a new idea called biochemical modulation based upon a preclinical biochemical and molecular pharmacological rationale. While 5-fluorouracil (5-FU) is a key drug for more than three decades, many a combination chemotherapy with 5-FU and other drugs such as methyl-CCNU, vincristine, streptozocin, mitomycin C and so on has been studied extensively only to show no significant improvement compared with monotherapy with 5-FU. Recently, the mechanisms of 5-FU action have been recognized more in detail biochemically, and it enabled us to try the drug in a more optimal way. For example, bolus i.v. infusion of 5-FU can produce a response rate of around 10% to 15% at most for advanced colorectal cancer. On the other hand, a more continuous mode of i.v. infusion, typically known as protracted i.v. infusion lasting up to 6 weeks or more, can produce the response rate of up to 40%. The difference underlying the mechanisms of action in these typical two administrative methods is that the main target can be RNA-directed cytotoxicity in the bolus type infusion and it can be shifted toward DNA-directed cytotoxicity in the continuous type infusion through the inhibition of thymidylate synthase (TS) enzyme activity which is relevant to DNA de novo synthesis. More importantly, investigations using clinical materials imply that DNA-directed cytotoxicity may be more relevant in a clinical setting, showing consistent findings between bench-top experiments and the clinical outcome. Given a precise knowledge about the mechanisms of 5-FU action, we could have developed a new type combination chemotherapy called biochemical modulation which manipulates non-cytotoxic agents or cytotoxic agents in non-cytotoxic level as modulators enhancing cytotoxicity of 5-FU biochemically. Among modulators, leucovorin (LV) has been shown to have a pivotal role in

Cost of cancer care for patients undergoing chemotherapy: The Elements of Cancer Care study.

PubMed

Ward, Robyn L; Laaksonen, Maarit A; van Gool, Kees; Pearson, Sallie-Anne; Daniels, Ben; Bastick, Patricia; Norman, Richard; Hou, Changhao; Haywood, Philip; Haas, Marion

2015-06-01

To determine the monthly treatment costs for each element of cancer care in patients receiving chemotherapy and to apportion the burden of cost by financing agent (Commonwealth, State government, private health insurer, patient). A cohort of 478 patients (54% breast, 33% colorectal and 13% non-small-cell lung cancer) were recruited from 12 centers representing metropolitan and regional settings in public and private sectors. Primary data were linked to secondary data held in New South Wales state (Admitted Patients and Emergency Department Data) and Commonwealth (Medicare and Pharmaceutical Benefits) databases. The monthly treatment costs of each element of care and the funding agent were calculated from secondary health data. Across all tumor types, the mean monthly treatment cost was $4162 (10%-90% quantiles $1018-$8098; range $2853 [adjuvant colorectal] to $5622 [metastatic lung]), with 54% of this cost borne by Commonwealth government, 26% by private health insurers, 14% by State government and 6% by patients. The mean monthly costs of treating metastatic disease were $1415 greater than those for adjuvant therapy. The mean monthly costs were contributed to by inpatient care ($1657, 40%), chemotherapy prescriptions ($1502, 36%), outpatient care ($452, 11%) and administration of chemotherapy ($364, 9%). All four funders have a shared incentive to reduce absolute monthly treatment costs since their proportional contribution is relatively constant for most tumor types and stages. There are opportunities to reduce cancer care costs by minimizing the risk of inpatient hospital admissions that arise from chemotherapy administration and by recognizing incentives for cost-shifting. © 2015 Wiley Publishing Asia Pty Ltd.

Single drug biomarker prediction for ER- breast cancer outcome from chemotherapy.

PubMed

Chen, Yong-Zi; Kim, Youngchul; Soliman, Hatem H; Ying, GuoGuang; Lee, Jae K

2018-06-01

ER-negative breast cancer includes most aggressive subtypes of breast cancer such as triple negative (TN) breast cancer. Excluded from hormonal and targeted therapies effectively used for other subtypes of breast cancer, standard chemotherapy is one of the primary treatment options for these patients. However, as ER- patients have shown highly heterogeneous responses to different chemotherapies, it has been difficult to select most beneficial chemotherapy treatments for them. In this study, we have simultaneously developed single drug biomarker models for four standard chemotherapy agents: paclitaxel (T), 5-fluorouracil (F), doxorubicin (A) and cyclophosphamide (C) to predict responses and survival of ER- breast cancer patients treated with combination chemotherapies. We then flexibly combined these individual drug biomarkers for predicting patient outcomes of two independent cohorts of ER- breast cancer patients who were treated with different drug combinations of neoadjuvant chemotherapy. These individual and combined drug biomarker models significantly predicted chemotherapy response for 197 ER- patients in the Hatzis cohort (AUC = 0.637, P  = 0.002) and 69 ER- patients in the Hess cohort (AUC = 0.635, P  = 0.056). The prediction was also significant for the TN subgroup of both cohorts (AUC = 0.60, 0.72, P  = 0.043, 0.009). In survival analysis, our predicted responder patients showed significantly improved survival with a >17 months longer median PFS than the predicted non-responder patients for both ER- and TN subgroups (log-rank test P -value = 0.018 and 0.044). This flexible prediction capability based on single drug biomarkers may allow us to even select new drug combinations most beneficial to individual patients with ER- breast cancer. © 2018 The authors.

[Extravasation of cytostatic agents: a serious complication of oncological treatment].

PubMed

Alfaro-Rubio, Alberto; Sanmartín, Onofre; Requena, Celia; Llombart, Beatriz; Botella-Estrada, Rafael; Nagore, Eduardo; Serra-Guillén, Carlos; Hueso, Luis; Guillén, Carlos

2006-04-01

The extravasation of cytostatic agents is a known, serious situation that can easily occur and cause chronic, irreversible damage. The incidence of extravasation ranges from 0.1 %-6.5 %, according to different studies. Many cases of extravasation can be prevented by systematizing the administration techniques for cytostatic agents. We present the clinical and histological characteristics of a series of patients with extravasation lesions. Included in the study were all patients treated with chemotherapy who developed localized lesions in the area of the cytostatic injection after extravasation was detected during administration. The patients were studied and followed up for a three-year period, from January 2000 to December 2003, inclusive. We found nine cases of extravasation among the 2,186 patients who were treated with chemotherapy, which represents an incidence of 0.41 %, and 3.4 % of all chemotherapy-induced skin lesions. The cytostatic agent most often involved was vinorelbine, and the most frequent location was the antecubital fossa. The intensity of the lesions made it necessary to delay the next cycle of treatment in 55 % of the cases. The histological findings varied depending on when the biopsy was done, showing panniculitis with low cellularity together with epidermal lesions attributable to direct cytotoxicity. The best treatment for extravasation is prevention, but when it has already occurred, measures vary depending on the cytostatic drug extravasated and the intensity of the lesions. Conservative measures are advisable before surgery.

Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells

PubMed Central

Chan, Tze-Sian; Pai, Vincent C.; Tan, Kok-Tong; Yen, Chia-Jui; Hsu, Shu-Ching; Chen, Wei-Yu; Shan, Yan-Shen; Lee, Michael T.; Chu, Jui-Mei

2016-01-01

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. PMID:27881732

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.

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.

Research Advances in Resistance to Platinum-based Chemotherapy in Lung Cancer.

PubMed

Zhang, Yajuan; Chang, De; Zhang, Jianpeng

2017-02-20

Platinum-based chemotherapy is the the cornerstone of treatment of many cancers. Combinations of platinum drugs with other agents are still the mainstream therapies for non-small cell lung cancer,showing significant effectiveness in an early phase. Along with the treatment,the tumor cells can become resistant to chemotherapy drugs,which affect the efficacy and prognosis. The mechanisms of drug resistance are complicated,including abnormal expressions of membrane proteins,enhanced DNA repair functions,abnormal regulation mechanisms of apoptosis,and enhanced cellular detoxification function. In this article we summarize some of the main mechanisms of platinum resistance in lung cancer cells,with an attempt to identify new potential target analogues or inhibitors and improve the efficacies of the combined use of platinum-based drugs.

Risk Factors for Febrile Neutropenia during Chemotherapy for HIV-Related Lymphoma

PubMed Central

Park, Jinyong; Kim, Tae Min; Hwang, Jeong-Hwan; Kim, Nak-Hyun; Choe, Pyoeng Gyun; Song, Kyoung-ho; Kim, Eu Suk; Park, Sang-Won; Kim, Hong Bin; Kim, Nam Joong; Oh, Myoung-don

2012-01-01

We evaluated risk factors for neutropenic fever and febrile prolonged neutropenia during vincristine-including chemotherapy to treat HIV-related lymphoma to investigate whether protease inhibitor (PI) treatment is associated with infectious complications due to drug interactions with chemotherapeutic agents. We included all HIV patients who received chemotherapy including vincristine for lymphoma at a single referral center in 1999-2010. Neutropenic fever was defined as absolute neutrophil count < 500 cells/µL with body temperature over 38℃; and prolonged neutropenia was defined if it persisted over 7 days. CODOX-M/IVAC and Stanford regimens were considered high-risk regimens for prolonged neutropenia. We analyzed 48 cycles of chemotherapy in 17 HIV patients with lymphoma. There were 22 neutropenic fever and 12 febrile prolonged neutropenia events. In multivariate analysis, neutropenic fever was associated with old age and low CD4 cell count, but not with PI use or ritonavir-boosted PI use. Low CD4 cell count and high-risk regimens were associated with febrile prolonged neutropenia. Neutropenic fever and febrile prolonged neutropenia is associated with old age, low CD4 cell count, and high-risk regimens, but not PI use, in HIV patients undergoing chemotherapy including vincristine for lymphoma. PMID:23255844

Thrombopoietic agents.

PubMed

Stasi, Roberto; Bosworth, Jenny; Rhodes, Elizabeth; Shannon, Muriel S; Willis, Fenella; Gordon-Smith, Edward C

2010-01-01

Thrombopoietin (TPO) is the key cytokine involved in thrombopoiesis, and is the endogenous ligand for the thrombopoietin receptor that is expressed on the surface of platelets, megakaryocytes, and megakaryocytic precursors. First-generation thrombopoietic agents were recombinant forms of human TPO, and their development was discontinued after prolonged thrombocytopenia due to neutralizing auto-antibodies cross-reacting with endogenous TPO was observed. Second-generation thrombopoiesis-stimulating molecules are now available, which have unique pharmacological properties and no sequence homology to endogenous TPO. Two of these new agents, romiplostim and eltrombopag, have already completed phase III trials in primary immune thrombocytopenia and have been granted marketing authorization for use in this disease. Phase II and III trials with these novel drugs are ongoing in other conditions characterized by thrombocytopenia, such as chemotherapy, chronic liver disease, and the myelodysplastic syndromes. Most of the other second-generation thrombopoietic growth factors are in early phase clinical development. Copyright 2010 Elsevier Ltd. All rights reserved.

Ion channels and neuronal hyperexcitability in chemotherapy-induced peripheral neuropathy

PubMed Central

Goldstein, Peter A

2017-01-01

Cancer is the second leading cause of death worldwide and is a major global health burden. Significant improvements in survival have been achieved, due in part to advances in adjuvant antineoplastic chemotherapy. The most commonly used antineoplastics belong to the taxane, platinum, and vinca alkaloid families. While beneficial, these agents are frequently accompanied by severe side effects, including chemotherapy-induced peripheral neuropathy (CPIN). While CPIN affects both motor and sensory systems, the majority of symptoms are sensory, with pain, tingling, and numbness being the predominant complaints. CPIN not only decreases the quality of life of cancer survivors but also can lead to discontinuation of treatment, thereby adversely affecting survival. Consequently, minimizing the incidence or severity of CPIN is highly desirable, but strategies to prevent and/or treat CIPN have proven elusive. One difficulty in achieving this goal arises from the fact that the molecular and cellular mechanisms that produce CPIN are not fully known; however, one common mechanism appears to be changes in ion channel expression in primary afferent sensory neurons. The processes that underlie chemotherapy-induced changes in ion channel expression and function are poorly understood. Not all antineoplastic agents directly affect ion channel function, suggesting additional pathways may contribute to the development of CPIN Indeed, there are indications that these drugs may mediate their effects through cellular signaling pathways including second messengers and inflammatory cytokines. Here, we focus on ion channelopathies as causal mechanisms for CPIN and review the data from both pre-clinical animal models and from human studies with the aim of facilitating the development of appropriate strategies to prevent and/or treat CPIN. PMID:28580836

Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

PubMed

Chen, Branson; Lee, Jong Bok; Kang, Hyeonjeong; Minden, Mark D; Zhang, Li

2018-04-24

While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as

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 ...

A Novel 3 Dimensional Stromal-based Model for In Vitro Chemotherapy Sensitivity Testing of Leukemia Cells

PubMed Central

Aljitawi, Omar S.; Li, Dandan; Xiao, Yinghua; Zhang, Da; Ramachandran, Karthik; Stehno-Bittel, Lisa; Van Veldhuizen, Peter; Lin, Tara L.; Kambhampati, Suman; Garimella, Rama

2014-01-01

The disparate responses of leukemia cells to chemotherapy in vivo, compared to in vitro, is partly related to the interactions of leukemic cells and the 3 dimensional (3D) bone marrow stromal microenvironment. We investigated the effects of chemotherapy agents on leukemic cell lines co-cultured with human bone marrow mesenchymal stem cell (hu-BM-MSC) in 3D. Comparison was made to leukemic cells treated in suspension, or grown on a hu-BM-MSC monolayer (2D conditions). We demonstrated that leukemic cells cultured in 3D were more resistant to drug-induced apoptosis compared to cells cultured in 2D or in suspension. We also demonstrated significant differences in leukemic cell response to chemotherapy using different leukemic cell lines cultured in 3D. We suggest that the differential responses to chemotherapy in 3D may be related to the expression of N-cadherin in the co-culture system. This unique model provides an opportunity to study leukemic cell responses to chemotherapy in 3D. PMID:23566162

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

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

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

PubMed

Whittaker, Alexandra L; Lymn, Kerry A; Wallace, Georgia L; Howarth, Gordon S

2016-01-01

Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

Changes in cross-sectional area of pulmonary vessels on chest computed tomography after chemotherapy in patients with advanced non-squamous non-small-cell lung cancer.

PubMed

Karayama, Masato; Inui, Naoki; Kusagaya, Hideki; Suzuki, Seiichiro; Inoue, Yusuke; Enomoto, Noriyuki; Fujisawa, Tomoyuki; Nakamura, Yutaro; Suda, Takafumi

2016-05-01

Chemotherapy is associated with a risk of vascular damage. Novel anti-angiogenic agents, which can directly affect tumor angiogenesis, are increasingly being used. However, the effects of these agents on normal vasculature are not well understood. Here, we evaluated the effects of chemotherapy in general, and the anti-angiogenic agent bevacizumab, more specifically, on the pulmonary vasculature in patients with advanced non-squamous non-small-cell lung cancer (NSCLC). For this, we used the cross-sectional area of pulmonary vessels (CSA), which is an easily measurable indicator of small pulmonary vasculature on non-contrast chest computed tomography (CT). We retrospectively reviewed CT scans of the lungs of 75 chemo-naïve patients with advanced non-squamous NSCLC, for measurement of CSA, before and after first-line platinum-based chemotherapy, using a semi-automatic image-processing program. Measured vessels were classified in two groups: small vessels with CSA <5 mm(2) and large vessels with CSA between 5 and 10 mm(2). The CSAs for each group of vessels were calculated and summed separately, and expressed as a percentage of the total lung area (%CSA<5 and %CSA5-10). Chemotherapy was associated with a selective decrease in small-diameter vessels, with a significant decrease in %CSA<5, but not %CSA5-10. When comparing chemotherapy with bevacizumab (n = 38) and without bevacizumab (n = 37), there was no significant difference in the reduction of %CSA<5. Platinum-based chemotherapy might induce small pulmonary vascular damage. Use of bevacizumab does not enhance the reduction in area of pulmonary vessels.

Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary

PubMed Central

Takahashi, Ryoko; Mabuchi, Seiji; Kawano, Mahiru; Sasano, Tomoyuki; Matsumoto, Yuri; Kuroda, Hiromasa; Kozasa, Katsumi; Hashimoto, Kae; Sawada, Kenjiro; Kimura, Tadashi

2016-01-01

Objective The objective of this study was to evaluate the antitumor effects of lurbinectedin as a single agent or in combination with existing anticancer agents for clear cell carcinoma (CCC) of the ovary, which is regarded as an aggressive, chemoresistant, histological subtype. Methods Using human ovarian CCC cell lines, the antitumor effects of lurbinectedin, SN-38, doxorubicin, cisplatin, and paclitaxel as single agents were assessed using the MTS assay. Then, the antitumor effects of combination therapies involving lurbinectedin and 1 of the other 4 agents were evaluated using isobologram analysis to examine whether these combinations displayed synergistic effects. The antitumor activity of each treatment was also examined using cisplatin-resistant and paclitaxel-resistant CCC sublines. Finally, we determined the effects of mTORC1 inhibition on the antitumor activity of lurbinectedin-based chemotherapy. Results Lurbinectedin exhibited significant antitumor activity toward chemosensitive and chemoresistant CCC cells in vitro. An examination of mouse CCC cell xenografts revealed that lurbinectedin significantly inhibits tumor growth. Among the tested combinations, lurbinectedin plus SN-38 resulted in a significant synergistic effect. This combination also had strong synergistic effects on both the cisplatin-resistant and paclitaxel-resistant CCC cell lines. Everolimus significantly enhanced the antitumor activity of lurbinectedin-based chemotherapies. Conclusions Lurbinectedin, a new agent that targets active transcription, exhibits antitumor activity in CCC when used as a single agent and has synergistic antitumor effects when combined with irinotecan. Our results indicate that lurbinectedin is a promising agent for treating ovarian CCC, both as a first-line treatment and as a salvage treatment for recurrent lesions that develop after platinum-based or paclitaxel treatment. PMID:26986199

The iron chelator deferasirox synergizes with chemotherapy to treat triple negative breast cancers.

PubMed

Tury, Sandrine; Assayag, Franck; Bonin, Florian; Chateau-Joubert, Sophie; Servely, Jean-Luc; Vacher, Sophie; Becette, Véronique; Caly, Martial; Rapinat, Audrey; Gentien, David; de la Grange, Pierre; Schnitzler, Anne; Lallemand, François; Marangoni, Elisabetta; Bièche, Ivan; Callens, Céline

2018-06-07

To ensure their high proliferation rate, tumor cells display an iron metabolic disorder with increased iron needs, making them more susceptible to iron deprivation. This vulnerability could be a therapeutic target. In breast cancers, the development of new therapeutic approaches is urgently needed for patients with triple negative tumors which frequently relapse after chemotherapy and suffer from a lack of targeted therapies. In this work, we demonstrated that deferasirox (DFX) synergizes with standard chemotherapeutic agents such as with doxorubicin, cisplatin and carboplatin to inhibit cell proliferation and induce apoptosis and autophagy in triple-negative breast cancer (TNBC) cell lines. Moreover, the combination of DFX with doxorubicin and cyclophosphamide delayed recurrences in breast cancer patient-derived xenografts without increasing the side-effects of chemotherapies alone or altering global iron storage of mice. Antitumor synergy of DFX and doxorubicin seems to involve down-regulation of the PI3K and NF-κB pathways. Iron deprivation in combination with chemotherapy could thus help to improve the effectiveness of chemotherapy in TNBC patients without increasing toxicities. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].

PubMed

Uchiyama, Kimio; Yamada, Manabu; Tamate, Shusuke; Iwasaki, Konomi; Mitomo, Keisuke; Nakayama, Seiichi

2015-09-01

The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy).

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

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

2017-07-01

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.

Profile of netupitant/palonosetron (NEPA) fixed dose combination and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV)

PubMed Central

Navari, Rudolph M

2015-01-01

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 antagonists, dexamethasone, and a neurokinin-1 (NK-1) 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, 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. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo®) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy. PMID:25552904

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

PubMed

Kim, Se-Hyuk; Yoo, Heon; Chang, Jong Hee; Kim, Chae-Yong; Chung, Dong Sup; Kim, Se Hoon; Park, Sung-Hae; Lee, Youn Soo; Yang, Seung Ho

2018-06-11

While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O 6 -methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m 2 ) on day 1 and procarbazine (60 mg/m 2 ) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Safety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients.

PubMed

Rossi, Antonio; Maione, Paolo; Gridelli, Cesare

2005-11-01

Non-small cell lung cancer (NSCLC) may be considered typical of advanced age. More than 50% of NSCLC patients are diagnosed at > 65 years of age and approximately one-third of all patients are > 70 years of age. Elderly patients tolerate chemotherapy poorly compared with their younger counterpart because of the progressive reduction of organ function and comorbidities related to age. For this reason, these patients are often not considered eligible for aggressive platinum-based chemotherapy, the standard medical treatment for advanced NSCLC. In clinical practice, single-agent chemotherapy should remain the standard treatment. Feasibility of platinum-based chemotherapy remains an open issue and has to be proven prospectively. Moreover, a multidimensional geriatric assessment for individualised treatment choice in NSCLC elderly patients is mandatory. This review focuses on the currently-available evidences for the treatment of elderly patients affected by advanced NSCLC with regards to the role and safety of platinum-based chemotherapy.

Applying Lean Sigma solutions to mistake-proof the chemotherapy preparation process.

PubMed

Aboumatar, Hanan J; Winner, Laura; Davis, Richard; Peterson, Aisha; Hill, Richard; Frank, Susan; Almuete, Virna; Leung, T Vivian; Trovitch, Peter; Farmer, Denise

2010-02-01

Errors related to high-alert medications, such as chemotherapeutic agents, have resulted in serious adverse events. A fast-paced application of Lean Sigma methodology was used to safeguard the chemotherapy preparation process against errors and increase compliance with United States Pharmacopeia 797 (USP 797) regulations. On Days 1 and 2 of a Lean Sigma workshop, frontline staff studied the chemotherapy preparation process. During Days 2 and 3, interventions were developed and implementation was started. The workshop participants were satisfied with the speed at which improvements were put to place using the structured workshop format. The multiple opportunities for error identified related to the chemotherapy preparation process, workspace layout, distractions, increased movement around ventilated hood areas, and variation in medication processing and labeling procedures. Mistake-proofing interventions were then introduced via workspace redesign, process redesign, and development of standard operating procedures for pharmacy staff. Interventions were easy to implement and sustainable. Reported medication errors reaching patients and requiring monitoring decreased, whereas the number of reported near misses increased, suggesting improvement in identifying errors before reaching the patients. Application of Lean Sigma solutions enabled the development of a series of relatively inexpensive and easy to implement mistake-proofing interventions that reduce the likelihood of chemotherapy preparation errors and increase compliance with USP 797 regulations. The findings and interventions are generalizable and can inform mistake-proofing interventions in all types of pharmacies.

Simultaneous hyperthermia-chemotherapy with controlled drug delivery using single-drug nanoparticles.

PubMed

Sato, Itaru; Umemura, Masanari; Mitsudo, Kenji; Fukumura, Hidenobu; Kim, Jeong-Hwan; Hoshino, Yujiro; Nakashima, Hideyuki; Kioi, Mitomu; Nakakaji, Rina; Sato, Motohiko; Fujita, Takayuki; Yokoyama, Utako; Okumura, Satoshi; Oshiro, Hisashi; Eguchi, Haruki; Tohnai, Iwai; Ishikawa, Yoshihiro

2016-04-22

We previously investigated the utility of μ-oxo N,N'- bis(salicylidene)ethylenediamine iron (Fe(Salen)) nanoparticles as a new anti-cancer agent for magnet-guided delivery with anti-cancer activity. Fe(Salen) nanoparticles should rapidly heat up in an alternating magnetic field (AMF), and we hypothesized that these single-drug nanoparticles would be effective for combined hyperthermia-chemotherapy. Conventional hyperthermic particles are usually made of iron oxide, and thus cannot exhibit anti-cancer activity in the absence of an AMF. We found that Fe(Salen) nanoparticles induced apoptosis in cultured cancer cells, and that AMF exposure enhanced the apoptotic effect. Therefore, we evaluated the combined three-fold strategy, i.e., chemotherapy with Fe(Salen) nanoparticles, magnetically guided delivery of the nanoparticles to the tumor, and AMF-induced heating of the nanoparticles to induce local hyperthermia, in a rabbit model of tongue cancer. Intravenous administration of Fe(Salen) nanoparticles per se inhibited tumor growth before the other two modalities were applied. This inhibition was enhanced when a magnet was used to accumulate Fe(Salen) nanoparticles at the tongue. When an AMF was further applied (magnet-guided chemotherapy plus hyperthermia), the tumor masses were dramatically reduced. These results indicate that our strategy of combined hyperthermia-chemotherapy using Fe(Salen) nanoparticles specifically delivered with magnetic guidance represents a powerful new approach for cancer treatment.

Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors.

PubMed

Davis, S T; Benson, B G; Bramson, H N; Chapman, D E; Dickerson, S H; Dold, K M; Eberwein, D J; Edelstein, M; Frye, S V; Gampe, R T; Griffin, R J; Harris, P A; Hassell, A M; Holmes, W D; Hunter, R N; Knick, V B; Lackey, K; Lovejoy, B; Luzzio, M J; Murray, D; Parker, P; Rocque, W J; Shewchuk, L; Veal, J M; Walker, D H; Kuyper, L F

2001-01-05

Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.

Alternating sequential chemotherapy with high-dose ifosfamide and doxorubicin/cyclophosphamide for adult non-small round cell soft tissue sarcomas.

PubMed

Kawai, Akira; Umeda, Toru; Wada, Takuro; Ihara, Koichiro; Isu, Kazuo; Abe, Satoshi; Ishii, Takeshi; Sugiura, Hideshi; Araki, Nobuhito; Ozaki, Toshifumi; Yabe, Hiroo; Hasegawa, Tadashi; Tsugane, Shoichiro; Beppu, Yasuo

2005-05-01

Doxorubicin and ifosfamide are the two most active agents used to treat soft tissue sarcomas. However, because of their overlapping side effects, concurrent administration to achieve optimal doses of each agent is difficult. We therefore conducted a Phase II trial to investigate the efficacy and feasibility of a novel alternating sequential chemotherapy regimen consisting of high dose ifosfamide and doxorubicin/cyclophosphamide in advanced adult non-small round cell soft tissue sarcomas. Adult patients with non-small round cell soft tissue sarcomas were enrolled. The treatment consisted of four sequential courses of chemotherapy that was planned for every 3 weeks. Cycles 1 and 3 consisted of ifosfamide (14 g/m(2)), and cycles 2 and 4 consisted of doxorubicin (60 mg/m(2)) and cyclophosphamide (1200 mg/m(2)). Forty-two patients (median age 47 years) were enrolled. Of the 36 assessable patients, 1 complete response and 16 partial responses were observed, for a response rate of 47.2%. Responses were observed in 57% of patients who had received no previous chemotherapy and 13% of those who had previously undergone chemotherapy. Grade 3-4 neutropenia was observed during 70% of all cycles. Sequential administration of high-dose ifosfamide and doxorubicin/cyclophosphamide has promising activity with manageable side effects in patients with advanced adult non-small round cell soft tissue sarcomas.

Combining chemotherapy with PD-1 blockade in NSCLC.

PubMed

Mathew, Matthen; Enzler, Thomas; Shu, Catherine A; Rizvi, Naiyer A

2018-06-01

Antitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small cell lung cancer (NSCLC). However, there remains a crucial need for better treatment strategies for the majority of patients with advanced NSCLC, particularly in the frontline setting. Chemotherapy can increase antigenicity via immunogenic cell death (ICD) of tumor cells as well as also reduce "off target" immunosuppression in the tumor microenvironment (TME). Combining chemotherapy with PD-1 blockade harnesses the potential synergy between these agents and has led to encouraging results in the up-front treatment of NSCLC. In this review, we summarize the preclinical rationale behind these combinations and review recent trial data demonstrating their efficacy. Copyright © 2018. Published by Elsevier Inc.

Risk of Subsequent Leukemia After a Solid Tumor in Childhood: Impact of Bone Marrow Radiation Therapy and Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allodji, Rodrigue S., E-mail: rodrigue.allodji@gustaveroussy.fr; Gustave Roussy, Villejuif; Paris Sud University, Orsay

Purpose: To investigate the roles of radiation therapy and chemotherapy in the occurrence of subsequent leukemia after childhood cancer. Methods and Materials: We analyzed data from a case-control study with 35 cases and 140 controls. The active bone marrow (ABM) was segmented into 19 compartments, and the radiation dose was estimated in each. The chemotherapy drug doses were also estimated to enable adjustments. Models capable of accounting for radiation dose heterogeneity were implemented for analysis. Results: Univariate analysis showed a significant trend in the increase of secondary leukemia risk with radiation dose, after accounting for dose heterogeneity (P=.046). This trendmore » became nonsignificant after adjustment for doses of epipodophyllotoxins, alkylating agents, and platinum compounds and the first cancer on multivariate analysis (P=.388). The role of the radiation dose appeared to be dwarfed, mostly by the alkylating agents (odds ratio 6.9, 95% confidence interval 1.9-25.0). Among the patients who have received >16 Gy to the ABM, the radiogenic risk of secondary leukemia was about 4 times greater in the subgroup with no alkylating agents than in the subgroup receiving ≥10 g/m{sup 2}. Conclusions: Notwithstanding the limitations resulting from the size of our study population and the quite systematic co-treatment with chemotherapy, the use of detailed information on the radiation dose distribution to ABM enabled consideration of the role of radiation therapy in secondary leukemia induction after childhood cancer.« less

Y-box-binding protein YB-1 identifies high-risk patients with primary breast cancer benefiting from rapidly cycled tandem high-dose adjuvant chemotherapy.

PubMed

Gluz, Oleg; Mengele, Karin; Schmitt, Manfred; Kates, Ronald; Diallo-Danebrock, Raihana; Neff, Frauke; Royer, Hans-Dieter; Eckstein, Niels; Mohrmann, Svjetlana; Ting, Evelyn; Kiechle, Marion; Poremba, Christopher; Nitz, Ulrike; Harbeck, Nadia

2009-12-20

To investigate the potential of Y-box-binding protein YB-1, a multifunctional protein linked to tumor aggressiveness and multidrug resistance, to identify patients with breast cancer likely to benefit from dose-intensified chemotherapy regimens. YB-1 was immunohistochemically determined in 211 primary tumors from the prospective, randomized West German Study Group WSG-AM-01 trial in high-risk (> or = 10 involved lymph-nodes) breast cancer (HRBC). Predictive impact of YB-1 was assessed by multivariate survival analysis, including time-varying factor-therapy interactions. At median follow-up of 61.7 months, patients receiving rapidly cycled tandem high-dose therapy (HD; two cycles [2x] epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) every 14 days, followed by 2x epirubicin 90 mg/m(2), cyclophosphamide 3,000 mg/m(2), and thiotepa 400 mg/m(2) every 21 days) had better disease-free survival (DFS; hazard ratio [HR] = 0.62; 95% CI, 0.44 to 0.89) and overall survival (OS; HR = 0.59; 95% CI, 0.4 to 0.89) than those receiving conventional dose-dense chemotherapy (DD; 4x epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), followed by 3x cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) every 14 days). High YB-1 was associated with aggressive tumor phenotype (negative steroid hormone receptor status, positive human epidermal growth factor receptor 2 and p53 status, high MIB-1, unfavorable tumor grade) and poor OS (median 78 v 97 months; P = .01). In patients with high YB-1, HD yielded a 63-month median DFS (P = .001) and a 46-month median OS advantage (P = .002) versus DD. In multivariate models, patients with high B-1 receiving HD (v DD) had one third the hazard rate after 20 months for DFS and one sixth after 40 months for OS. In a randomized prospective cancer therapy trial, for the first time, a strong predictive impact of YB-1 on survival has been demonstrated: enhanced benefit from HD (v DD) therapy occurs in HRBC with high YB

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.

Targeting Cancer using Polymeric Nanoparticle mediated Combination Chemotherapy

PubMed Central

Gad, Aniket; Kydd, Janel; Piel, Brandon; Rai, Prakash

2016-01-01

Cancer forms exhibiting poor prognosis have been extensively researched for therapeutic solutions. One of the conventional modes of treatment, chemotherapy shows inadequacy in its methodology due to imminent side-effects and acquired drug-resistance by cancer cells. However, advancements in nanotechnology have opened new frontiers to significantly alleviate collateral damage caused by current treatments via innovative delivery techniques, eliminating pitfalls encountered in conventional treatments. Properties like reduced drug-clearance and increased dose efficacy by the enhanced permeability and retention effect deem nanoparticles suitable for this application. Optimization of size, surface charge and surface modifications have provided nanoparticles with stealth properties capable of evading immune responses, thus deeming them as excellent carriers of chemotherapeutic agents. Biocompatible and biodegradable forms of polymers enhance the bioavailability of chemotherapeutic agents, and permit a sustained and time-dependent release of drugs which is a characteristic of their composition, thereby providing a controlled therapeutic approach. Studies conducted in vitro and animal models have also demonstrated a synergism in cytotoxicity given the mechanism of action of anticancer drugs when administered in combination providing promising results. Combination therapy has also shown implications in overcoming multiple-drug resistance, which can however be subdued by the adaptable nature of tumor microenvironment. Surface modifications with targeting moieties can therefore feasibly increase nanoparticle uptake by specific receptor-ligand interactions, increasing dose efficacy which can seemingly overcome drug-resistance. This article reviews recent trends and investigations in employing polymeric nanoparticles for effectively delivering combination chemotherapy, and modifications in delivery parameters enhancing dose efficacy, thus validating the potential in this

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.

Glutathione responsive micelles incorporated with semiconducting polymer dots and doxorubicin for cancer photothermal-chemotherapy

NASA Astrophysics Data System (ADS)

Cai, Zhixiong; Zhang, Da; Lin, Xinyi; Chen, Yunzhu; Wu, Ming; Wei, Zuwu; Zhang, Zhenxi; Liu, Xiaolong; Yao, Cuiping

2017-10-01

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.

Laser assisted immunotherapy (LIT) for chemotherapy-resistant neoplasms: recent case reports

NASA Astrophysics Data System (ADS)

Nordquist, Robert E.; Bahavar, Cody; Zhou, Feifan; Hode, Tomas; Chen, Wei R.; Li, Xiaosong; Naylor, Mark F.

2014-02-01

T-cell stimulators such as anti-CTLA-4 antibodies enhance immunologic responses to chemotherapy-resistant solid tumors, such as melanoma, advanced breast cancer, ovarian cancer and pancreatic cancer. The efficacy of these new immunotherapy agents can in theory be enhanced substantially by therapies that stimulate new immunologic (T-cell) responses against the tumor. Laser immunotherapy (LIT) with imiquimod and InCVAX are techniques that produce useful responses in patients with advanced melanoma, the prototypical chemotherapy resistant solid tumor. The mechanism of action of these therapies is thought to be immunological, including the development of new T-cell responses. We have therefore been combining LIT using imiquimod and InCVAX treatment with the new T-cell stimulators (ipilimumab) in cases of stage IV melanoma. While still anecdotal, the use of novel combinations of immunologic therapies should provide much improved responses for chemotherapy-resistant solid tumors (such as melanoma) than was previously possible. Newer T-cell stimulating drugs such as the anti-PD-1 antibodies and anti-PD-L1 antibodies will make this general approach to treating chemoresistant advanced tumors even more effective in the future.

Maintenance therapy with toceranib following doxorubicin-based chemotherapy for canine splenic hemangiosarcoma.

PubMed

Gardner, Heather L; London, Cheryl A; Portela, Roberta A; Nguyen, Sandra; Rosenberg, Mona P; Klein, Mary K; Clifford, Craig; Thamm, Douglas H; Vail, David M; Bergman, Phil; Crawford-Jakubiak, Martin; Henry, Carolyn; Locke, Jennifer; Garrett, Laura D

2015-06-11

Spenic hemangiosarcoma (HSA) in dogs treated with surgery alone is associated with short survival times, and the addition of doxorubicin (DOX) chemotherapy only modestly improves outcome. The purpose of this study was to evaluate the impact of toceranib administration on progression free survival in dogs with stage I or II HSA following splenectomy and single agent DOX chemotherapy. We hypothesized that dogs with splenic HSA treated with adjuvant DOX followed by toceranib would have prolonged disease-free interval (DFI) and overall survival time (OS) when compared to historical dogs treated with DOX-based chemotherapy alone. Dogs with stage I or II splenic HSA were administered 5 cycles of single-agent DOX every 2 weeks beginning within 14 days of splenectomy. Dogs were restaged 2 weeks after completing DOX, and those without evidence of metastatic disease began toceranib therapy at 3.25 mg/kg every other day. Forty-three dogs were enrolled in this clinical trial. Seven dogs had evidence of metastatic disease either before or at re-staging, and an additional 3 dogs were found to have metastatic disease within 1 week of toceranib administration. Therefore 31 dogs went on to receive toceranib following completion of doxorubicin treatment. Twenty-five dogs that received toceranib developed metastatic disease. The median disease free interval for all dogs enrolled in this study (n = 43) was 138 days, and the median disease free interval for those dogs that went on to receive toceranib (n = 31) was 161 days. The median survival time for all dogs enrolled in this study was 169 days, and the median survival time for those dogs that went on to receive toceranib was 172 days. The use of toceranib following DOX chemotherapy does not improve either disease free interval or overall survival in dogs with stage I or II HSA.

Forcing the vicious circle: sarcopenia increases toxicity, decreases response to chemotherapy and worsens with chemotherapy.

PubMed

Bozzetti, F

2017-09-01

Sarcopenia has recently emerged as a new condition that, independently from malnutrition, may adversely affect the prognosis of cancer patients. Purpose of this narrative review is to define the prevalence of sarcopenia in different primaries, its role in leading to chemotherapy toxicity and decreased compliance with the oncological therapy and the effect of some drugs on the onset of sarcopenia. Finally, the review aims to describe the current approaches to restore the muscle mass through nutrition, exercise and anti-inflammatory agents or multimodal programmes with a special emphasis on the results of randomized controlled trials. The examination of the computed tomography scan at the level of the third lumbar vertebra-a common procedure for staging many tumours-has allowed the oncologist to evaluate the muscle mass and to collect many retrospective data on the prevalence of sarcopenia and its clinical consequences. Sarcopenia is a condition affecting a high percentage of patients with a range depending on type of primary tumour and stage of disease. It is noteworthy that patients may be sarcopenic even if their nutritional status is apparently maintained or they are obese. Sarcopenic patients exhibited higher chemotherapy toxicity and poorer compliance with oncological treatments. Furthermore, several antineoplastic drugs appeared to worsen the sarcopenic status. Therapeutic approaches are several and this review will focus on those validated by randomized controlled trials. They include the use of ω-3-enriched oral nutritional supplements and orexigenic agents, the administration of adequate high-protein regimens delivered enterally or parenterally, and programmes of physical exercise. Better results are expected combining different procedures in a multimodal approach. In conclusion, there are several premises to prevent/treat sarcopenia. The oncologist should coordinate this multimodal approach by selecting priorities and sequences of treatments and then

A Phase II/III Randomized, Placebo-Controlled, Double-Blind Clinical Trial of Ginger (Zingiber officinale) for Nausea Caused by Chemotherapy for Cancer: A Currently Accruing URCC CCOP Cancer Control Study.

PubMed

Hickok, Jane T; Roscoe, Joseph A; Morrow, Gary R; Ryan, Julie L

2007-09-01

Despite the widespread use of 5-HT3 receptor antagonist antiemetics such as ondansetron and granistron, up to 70% of patients with cancer receiving highly emetogenic chemotherapy agents experience postchemotherapy nausea and vomiting. Delayed postchemotherapy nausea (nausea that occurs >/= 24 hours after chemotherapy administration) and anticipatory nausea (nausea that develops before chemotherapy administration, in anticipation of it) are poorly controlled by currently available antiemetic agents. Scientific studies suggest that ginger (Zingiber officinale) might have beneficial effects on nausea and vomiting associated with motion sickness, surgery, and pregnancy. In 2 small studies of patients with cancer receiving chemotherapy, addition of ginger to standard antiemetic medication further reduced the severity of postchemotherapy nausea. This article describes a phase II/III randomized, dose-finding, placebo-controlled, double-blind clinical trial to assess the efficacy of ginger for nausea associated with chemotherapy for cancer. The study is currently being conducted by private practice oncology groups that are funded by the National Cancer Institute's Community Clinical Oncology Program and affiliated with the University of Rochester Cancer Center Community Clinical Oncology Program Research Base.

Stimuli-free programmable drug release for combination chemo-therapy

NASA Astrophysics Data System (ADS)

Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

2016-06-01

Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

Potential Proinvasive or Metastatic Effects of Preclinical Antiangiogenic Therapy Are Prevented by Concurrent Chemotherapy.

PubMed

Paez-Ribes, Marta; Man, Shan; Xu, Ping; Kerbel, Robert S

2015-12-15

To resolve a controversy involving the therapeutic impact of antiangiogenic drugs and particularly antibodies targeting the VEGF pathway, namely, a body of preclinical mouse therapy studies showing such drugs can promote invasion and/or distant metastasis when used as monotherapies. In contrast, clinical studies have not shown such promalignancy effects. However, most such clinical studies have involved patients also treated with concurrent chemotherapy highlighting the possibility that chemotherapy may prevent any potential promalignancy effect caused by an antiangiogenic drug treatment. The impact of antiangiogenic therapy using DC101, an antibody targeting mouse VEGFR-2 with or without concurrent chemotherapy was assessed in multiple human breast cancer xenograft models, where impact on orthotopic primary tumors was evaluated. Metastasis was also assessed during adjuvant and neoadjuvant plus adjuvant therapy, after surgical resection of primary tumors, with the same combination therapies. Antiangiogenic therapy, while blunting tumor volume growth, was found to increase local invasion in multiple primary tumor models, including a patient-derived xenograft, but this effect was blocked by concurrent chemotherapy. Similarly, the combination of paclitaxel with DC101 caused a marked reduction of micro- or macrometastatic disease in contrast to DC101 monotherapy, which was associated with small increases in metastatic disease. Conventional wisdom is that targeted biologic antiangiogenic agents such as bevacizumab when used with chemotherapy increase the efficacy of the chemotherapy treatment. Our results suggest the reverse may be true as well-chemotherapy may improve the impact of antiangiogenic drug treatment and, as a result, overall efficacy. Clin Cancer Res; 21(24); 5488-98. ©2015 AACR. ©2015 American Association for Cancer Research.

Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

PubMed Central

Rabanal, Connie; Ruiz, Rossana; Neciosup, Silvia; Gomez, Henry

2017-01-01

Triple negative breast cancer (TNBC) accounts for 15%-20% of all breast cancer, and is still defined as what it is not. Currently, TNBC is the only type of breast cancer for which there are no approved targeted therapies and maximum tolerated dose chemotherapy with taxanes and anthracycline-containing regimens is still the standard of care in both the neoadjuvant and adjuvant settings. In the last years, metronomic chemotherapy (MC) is being explored as an alternative to improve outcomes in TNBC. In the neoadjuvant setting, purely metronomic and hybrid approaches have been developed with the objective of increasing complete pathologic response (pCR) and prolonging disease free survival. These regimens proved to be very effective achieving pCR rates between 47%-60%, but at the cost of great toxicity. In the adjuvant setting, MC is used to intensify adjuvant chemotherapy and, more promisingly, as maintenance therapy for high-risk patients, especially those with no pCR after neoadjuvant chemotherapy. Considering the dismal prognosis of TNBC, any strategy that potentially improves outcomes, specially being the oral agents broadly available and inexpensive, should be considered and certainly warrants further exploration. Finally, the benefit of MC needs to be validated in properly designed clinical trials were the selection of the population is the key. PMID:29291168

A retrospective analysis to identify the factors affecting infection in patients undergoing chemotherapy.

PubMed

Park, Ji Hyun; Kim, Hyeon-Young; Lee, Hanna; Yun, Eun Kyoung

2015-12-01

This study compares the performance of the logistic regression and decision tree analysis methods for assessing the risk factors for infection in cancer patients undergoing chemotherapy. The subjects were 732 cancer patients who were receiving chemotherapy at K university hospital in Seoul, Korea. The data were collected between March 2011 and February 2013 and were processed for descriptive analysis, logistic regression and decision tree analysis using the IBM SPSS Statistics 19 and Modeler 15.1 programs. The most common risk factors for infection in cancer patients receiving chemotherapy were identified as alkylating agents, vinca alkaloid and underlying diabetes mellitus. The logistic regression explained 66.7% of the variation in the data in terms of sensitivity and 88.9% in terms of specificity. The decision tree analysis accounted for 55.0% of the variation in the data in terms of sensitivity and 89.0% in terms of specificity. As for the overall classification accuracy, the logistic regression explained 88.0% and the decision tree analysis explained 87.2%. The logistic regression analysis showed a higher degree of sensitivity and classification accuracy. Therefore, logistic regression analysis is concluded to be the more effective and useful method for establishing an infection prediction model for patients undergoing chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeted Agents Active Against Breast Cancer: Q&A

Cancer.gov

ALTTO was a clinical trial designed to determine whether the combination of the monoclonal antibody trastuzumab (Herceptin) and the drug lapatinib (Tykerb) was more effective in treating HER2/ErbB2-positive breast cancer when combined with chemotherapy than either agent alone. Results from ALTTO did not show additional benefit from combining lapatinib and trastuzumab compared with trastuzumab treatment alone.

A supramolecular nanoparticle system based on β-cyclodextrin-conjugated poly-l-lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma.

PubMed

Xiong, Qingqing; Cui, Mangmang; Bai, Yang; Liu, Yuanyuan; Liu, Di; Song, Tianqiang

2017-07-01

A novel supramolecular nanoparticle system with core-shell structure was designed based on β-cyclodextrin-conjugated poly-l-lysine (PLCD) and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma (HCC). PLCD was synthesized by the conjugation of monoaldehyde activated β-cyclodextrin with poly-l-lysine via Shiff's base reaction. Doxorubicin, as a model therapeutic drug, was included into the hydrophobic cavity of β-cyclodextrin in PLCD through host-guest interaction. OligoRNA, as a model gene, was further condensed into the inclusion complexes by electrostatic interaction to form oligoRNA and doxorubicin co-loaded supramolecular nanoparticle system. Hyaluronic acid, which is often over-expressed by HCC cells, was coated on the surface of the above nanoparticles to construct HCC-targeted nanoparticle system. These nanoparticles had regular spherical shape with classic "core-shell" structure, and their size and zeta potential were 195.8nm and -22.7mV, respectively. The nanoparticles could effectively deliver doxorubicin and oligoRNA into HCC cells via CD44 receptor-mediated endocytosis and significantly inhibit the cell proliferation. In the nude mice bearing MHCC-97H tumor, the nanoparticles could be efficiently accumulated in the tumor, suggesting their strong hepatoma-targeting capability. These findings demonstrated that this novel supramolecular nanoparticle system had a promising potential for combining gene therapy and chemotherapy to treat HCC. Copyright © 2017 Elsevier B.V. All rights reserved.

New developments in chemotherapy of advanced breast cancer.

PubMed

Lebwohl, D E; Canetta, R

1999-01-01

Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [1]. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimized; Gianni reported a 94% objective response rate using Dox 60 mg/m2 followed by paclitaxel 175 mg/m2 given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies. Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in > 25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4-(phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-217380-01), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomized trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems

PubMed Central

Wu, Min; Frieboes, Hermann B.; Chaplain, Mark A.J.; McDougall, Steven R.; Cristini, Vittorio; Lowengrub, John

2014-01-01

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but leads to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the

Chemotherapy-induced nausea and vomiting in routine practice: a European perspective.

PubMed

Glaus, Agnes; Knipping, Cornelia; Morant, Rudolf; Böhme, Christel; Lebert, Burkhard; Beldermann, Frank; Glawogger, Bernhard; Ortega, Paz Fernandez; Hüsler, André; Deuson, Robert

2004-10-01

The aim of this study was to evaluate the occurrence of chemotherapy-induced nausea and vomiting (CINV) and its effect on patients' ability to carry out daily life activities following moderately to highly emetogenic, first-cycle chemotherapy in routine practice in cancer centers of four different European countries. This was a prospective, cross-sectional, nonrandomized, self-assessment study in 249 patients enrolled from cancer centers in Spain, Austria, Germany, and Switzerland. The study population consisted of 78% women, with a mean age of 54. Breast, lung, and ovarian cancers made up 75% of all cancers in the study. Patients received a mean of 2.0 chemotherapy agents and 2.5 antiemetic drugs. A total of 450 emetic episodes experienced by 243 patients was recorded over 5 days following chemotherapy, with an average of 1.8 episodes per patient (range: 0-28). A higher percentage of patients (38%) suffered from delayed compared to acute emesis (13%). Between 42% and 52% of all patients suffered from nausea (visual analogue scale > or = 5 mm) on any one day, peaking at day 3. Using the Functional Living Index for Emesis (FLIE) questionnaire, 75% of patients with nausea and 50% with vomiting reported a negative impact of these conditions on performance of daily living. CINV remains a significant problem in routine practice, particularly in the delayed phase posttreatment. Overall, CINV had a negative impact on patients' daily life.

Chemotherapy drug handling in first opinion small animal veterinary practices in the United Kingdom: results of a questionnaire survey.

PubMed

Edery, E G

2017-05-27

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. British Veterinary Association.

Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy

NASA Astrophysics Data System (ADS)

Wang, Wenjing; Fang, Chenjie; Wang, Xiaozhu; Chen, Yuxi; Wang, Yaonan; Feng, Wei; Yan, Chunhua; Zhao, Ming; Peng, Shiqi

2013-06-01

Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy.Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy. Electronic supplementary information (ESI) available: Experimental details of the synthesis and in vitro and in vivo assays. See DOI: 10.1039/c3nr00227f

Cytokine-mediated blood brain barrier disruption as a conduit for cancer/chemotherapy-associated neurotoxicity and cognitive dysfunction.

PubMed

Wardill, Hannah R; Mander, Kimberley A; Van Sebille, Ysabella Z A; Gibson, Rachel J; Logan, Richard M; Bowen, Joanne M; Sonis, Stephen T

2016-12-15

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. © 2016 UICC.

Behavioral and Psychological Predictors of Chemotherapy Adherence in Patients with Advanced Non-Small-Cell Lung Cancer

PubMed Central

Greer, Joseph A.; Pirl, William F.; Park, Elyse R.; Lynch, Thomas J.; Temel, Jennifer S.

2013-01-01

Objective Dose delays and reductions in chemotherapy due to hematologic toxicities are common among patients with advanced non-small-cell lung cancer (NSCLC). However, limited data exist on behavioral or psychological predictors of chemotherapy adherence. The goal of this study was to explore the frequency and clinical predictors of infusion dose delays and reductions in this patient population. Methods Fifty patients newly diagnosed with advanced NSCLC of high performance status (ECOG PS=0-1) completed baseline assessments on quality of life (FACT-L) and mood (HADS) within eight weeks of diagnosis. Participants were followed prospectively for six months. Chemotherapy dosing data came from medical chart review. Results All patients received chemotherapy during the course of the study, beginning with either a platinum-based doublet (74%), an oral epidermal growth factor receptor-tyrosine kinase inhibitor (14%), or a parenteral single agent (12%). Forty percent (N=20) of patients had either a dose delay (38%) and/or reduction (16%) in their scheduled infusions. Fisher’s exact tests showed that patients who experienced neutropenia, smoked at the time of diagnosis, or reported heightened baseline anxiety were significantly more likely to experience dose delays or reductions. There were no associations between chemotherapy adherence and patient demographics, performance status, or quality of life. Conclusion In this sample, over one-third of patients with advanced NSCLC experienced either a dose delay or reduction in prescribed chemotherapy regimens. Behavioral and psychological factors, such as tobacco use and anxiety symptoms, appear to play an important role in chemotherapy adherence, though further study is required to confirm these findings. PMID:19027443

The Alkylating-HDAC Inhibition Fusion Principle: Taking Chemotherapy to the Next Level with the First in Class Molecule EDO-S101.

PubMed

Mehrling, Thomas; Chen, Yi

2016-01-01

Chemotherapy may still be an essential component to treat cancer in combination with new targeted therapies. But chemotherapy needs to get smarter in order to make those combination regimens more effective and also more tolerable, particularly for an aging population. We describe the first time the synthesis and pharmacological testing of a fusion molecule comprising of the alkylator bendamustine and the HDAC-inhibitor vorinostat. The drug was designed to allow for the exploitation of both mechanisms of action simultaneously with the goal to provide a molecule with superior efficacy over the single agents. The pharmacological testing confirms the full functional capacity of both moieties and encouraging pharmacological data raises the hope that the drug may turn out to be a great addition to the armentarium of anticancer agents.

Fc gamma receptor 3a genotype predicts overall survival in follicular lymphoma patients treated on SWOG trials with combined monoclonal antibody plus chemotherapy but not chemotherapy alone

PubMed Central

Persky, Daniel O.; Dornan, David; Goldman, Bryan H.; Braziel, Rita M.; Fisher, Richard I.; LeBlanc, Michael; Maloney, David G.; Press, Oliver W.; Miller, Thomas P.; Rimsza, Lisa M.

2012-01-01

Background Fc gamma receptor polymorphisms were linked to outcome in follicular lymphoma patients treated with single-agent rituximab, an anti-CD20 monoclonal antibody. In particular, 158F/F genotype of Fc gamma receptor 3A and 131R/R genotype of Fc gamma receptor 2A correlated with worse outcome compared to high-affinity 158V/V and 131H/H, respectively. We examined this association in the context of anti-CD20 monoclonal antibody combined with chemotherapy, as compared to chemotherapy alone, in follicular lymphoma patients treated on SWOG clinical trials. Design and Methods Tissue from 142 SWOG patients treated with chemotherapy alone (protocol S8809, n=70) or combined chemotherapy and anti-CD20 monoclonal antibody (rituximab and Iodine I-131 tositumomab on protocols S9800 and S9911, n=30 and 42, respectively) was analyzed. DNA was extracted and assayed for Fc gamma receptor 3A V158F and 2A R131H polymorphisms using a TaqMan SNP assay. Stratified Cox’s regression was used to assess association with overall survival. Results For Fc gamma receptor 3A, there was an association with overall survival in the combination therapy trials but not in the chemotherapy-only trial. Having at least one Fc gamma receptor 3A V allele was associated with improved overall survival versus F/F (HR=0.33, 95% CI, 0.11, 0.96, P=0.042). For overall survival, there was evidence of a statistical interaction between the use of mAb and the number of V alleles (0, 1, or 2) (P=0.006). There was no such association for Fc gamma receptor 2A. Conclusions Fc gamma receptor 3A polymorphism status may be predictive of survival in follicular lymphoma patients receiving treatments containing an anti-CD20 antibody but not treatment with chemotherapy alone. Thus, Fc gamma receptor 3A polymorphisms may be important to consider in designing new follicular lymphoma trials and new anti-CD20 monoclonal antibodies. PMID:22271896

Development of regional chemotherapies: feasibility, safety and efficacy in clinical use and preclinical studies

PubMed Central

Cai, Shuang; Bagby, Taryn R; Forrest, M Laird

2011-01-01

Conventional oral and intravenous chemotherapies permeate throughout the body, exposing healthy tissues to similar cytotoxic drug levels as tumors. This leads to significant dose-limiting toxicities that may prevent patients from receiving sufficient treatment to overcome cancers. Therefore, a number of locoregional drug-delivery strategies have been evaluated and implemented in preclinical studies, clinical trials and in practice, in the past decades to minimize systemic toxicities from chemotherapeutic agents and to improve treatment outcomes. Localized treatment is beneficial because many cancers, such as melanoma, peritoneal cancer and breast cancer, advance locally adjacent to the site of the primary tumors prior to their circulatory invasion. In this article, we will review the feasibility, safety and efficacy of multiple localized chemotherapies in clinical use and preclinical development. PMID:22229080

The addition of gemtuzumab ozogamicin to chemotherapy in adult patients with acute myeloid leukemia.

PubMed

Kell, Jonathan

2016-01-01

The treatment of acute myeloid leukaemia has remained largely unchanged for the last 30 years since the advent of combination chemotherapy with cytarabine arabinoside and daunorubicin with remission rates around 70% but with long term survival still only around 40% in young adults. Doses of chemotherapy have been pushed to the limit of toxicity. Gemtuzumab ozogamicin allows additional chemotherapy to be delivered to the leukaemic cells without significantly adding to toxicity since the active agent is coupled to a monoclonal anti-CD33 antibody. It was approved by the FDA in 2000 for the treatment of elderly patients with relapsed CD33 positive AML at a dose of 9mg/m(2) on two days two weeks apart. Almost at once, questions were raised about its safety, with a particular liver signal, and it was voluntarily withdrawn from practice in 2010. Many groups have been examining the role of gemtuzumab ozogamicin in combination with chemotherapy, usually at lower doses than originally recommended, with varying degrees of success and toxicity and gemtuzumab ozogamicin is now entering a period of rehabilitation. Currently it is only commercially available in Japan although it is currently also available in the UK Bloodwise AML18 study.

Harnessing the internet cloud for managing drug interactions with chemotherapy regimens in patients with cancer suffering from depression.

PubMed

Yap, Kevin Yi-Lwern; Ho, Yasmin Xiu Xiu; Chui, Wai Keung; Chan, Alexandre

2010-11-01

Concomitant use of anticancer drugs (ACDs) and antidepressants (ADs) in the treatment of depression in patients with cancer may result in potentially harmful drug-drug interactions (DDIs). It is crucial that clinicians make timely, accurate, safe and effective decisions regarding drug therapies in patients. The ubiquitous nature of the internet or "cloud" has enabled easy dissemination of DDI information, but there is currently no database dedicated to allow searching of ACD interactions by chemotherapy regimens. We describe the implementation of an AD interaction module to a previously published oncology-specific DDI database for clinicians which focuses on ACDs, single-agent and multiple-agent chemotherapy regimens. Drug- and DDI-related information were collated from drug information handbooks, databases, package inserts, and published literature from PubMed, Scopus and Science Direct. Web documents were constructed using Adobe software and programming scripts, and mounted on a domain served from the internet cloud. OncoRx is an oncology-specific DDI database whose structure is designed around all the major classes of ACDs and their frequently prescribed chemotherapy regimens. There are 117 ACDs and 256 regimens in OncoRx, and it can detect over 1 500 interactions with 21 ADs. Clinicians are provided with the pharmacokinetic parameters of the drugs, information on the regimens and details of the detected DDIs during an interaction search. OncoRx is the first database of its kind which allows detection of ACD and chemotherapy regimen interactions with ADs. This tool will assist clinicians in improving clinical response and reducing adverse effects based on the therapeutic and toxicity profiles of the drugs.

One-pot synthesis of dextran decorated reduced graphene oxide nanoparticles for targeted photo-chemotherapy.

PubMed

Hu, Yanfang; He, Liang; Ding, Jianxun; Sun, Diankui; Chen, Li; Chen, Xuesi

2016-06-25

Graphene-based nanocarriers show great potential in photo-chemotherapy, however, to prepare desired reduced graphene oxide (rGO) nanoparticles in a facile way is still a challenge. Herein, a novel strategy has been presented to prepare rGO nanoparticle using dextran (Dex) as a reducing agent. In this strategy, Dex was directly conjugated on rGO by hydrogen bond and then self-assemble to form rGO/Dex nanoparticles. After decorated by dextran, rGO-based nanoparticles not only show excellent biocompatibility but also can load anticancer drug for photo-chemotherapy. The data of fourier transform infrared (FT-IR) analysis, Raman spectrum analysis, thermos-gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), the transmission electron microscope (TEM) image and dynamic light scattering (DLS) measurements powerfully proved that the stable rGO-based nanoparticles with desired nanosize have been successfully prepared. To verify the photo-chemotherapy, anticancer drug, doxorubicin (DOX), has been loaded on rGO/Dex nanoparticles (rGO/DOX/Dex). And RGD, a kind of oligopeptide which can improve the intracellular uptake by αvβ3 recognition, also has been introduced (rGO/DOX/RDex). Compared with single chemotherapy, rGO/DOX/Dex and rGO/DOX/RDex combining the local specific chemotherapy and external near-infrared (NIR) photo-thermal therapy show higher therapeutic efficacy, endowing the desired rGO-based nanoparticle with great potential for cancer treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemotherapy induced Takotsubo cardiomyopathy

PubMed Central

Goel, Sunny; Sharma, Abhishek; Garg, Aakash; Chandra, Abhinav; Shetty, Vijay

2014-01-01

Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine. PMID:25325068

Chemotherapy induced Takotsubo cardiomyopathy.

PubMed

Goel, Sunny; Sharma, Abhishek; Garg, Aakash; Chandra, Abhinav; Shetty, Vijay

2014-10-16

Chemotherapy has been linked with Takotsubo cardiomyopathy. Most of the literature on chemotherapy associated Takotsubo cardiomyopathy is on the drug 5-fluorouracil. In this report, we describe the case of a 55-year-old Asian male who developed Takotsubo cardiomyopathy while receiving dual chemotherapy with cytarabine and daunorubicin for acute myeloid leukemia. To our knowledge, it is the first case of Takotsubo cardiomyopathy associated with daunorubicin and/or cytarabine.

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.

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

PubMed

Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS <10), for whom ST is deemed appropriate for toxicity. The primary objective was to estimate the agreement in chemotherapy choice (ST vs. RT) between the treating physician and the CTRS using a κ statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS <10, and 17 had CTRS ≥10), and 20 patients received RT (12 had CTRS ≥10, and 8 had CTRS <10), with minimal agreement in chemotherapy choice (κ = 0.14; 95% CI, -0.10 to 0.38). Grade 3-4 toxicity and hospitalization occurred in 60% and 27% of 55 patients with follow-up data, respectively. Among patients receiving ST, patients with CTRS ≥10 had a higher incidence of toxicity (88% vs. 40%, p  = .006) and hospitalization (50% vs. 15%, p  = .03) than those with CTRS <10. Older patients with cancer with a high CTRS who receive combination chemotherapy have an exceedingly high rate of severe toxicity and hospitalization. The potential utility of the chemotherapy toxicity risk score (CTRS) in old adults with advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity.

PubMed

Ojha, Shreesh; Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem; Rajesh, Mohanraj

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage.

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

PubMed Central

Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in the literature reveal partial amelioration of CSP-induced renal toxicity, stressing the need to develop potent combinatorial/synergistic agents for the mitigation of renal toxicity. However, the ideal renoprotective adjuvant should not interfere with the anticancer efficacy of CSP. In this review, we have discussed the progress made in utilizing plant-derived agents (phytochemicals) to combat CSP-induced nephrotoxicity in preclinical studies. Furthermore, we have also presented strategies to utilize phytochemicals as prototypes for the development of novel renoprotective agents for counteracting chemotherapy-induced renal damage. PMID:27774117

Development and Applications of Photo-triggered Theranostic Agents

PubMed Central

Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

2010-01-01

Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

Clostridium difficile Infection: Associations with Chemotherapy, Radiation Therapy, and Targeting Therapy Treatments.

PubMed

Peretz, Avi; Shlomo, Izhar Ben; Nitzan, Orna; Bonavina, Luigi; Schaffer, Pmela M; Schaffer, Moshe

2016-01-01

Although mucositis, diarrhea, and constipation as well as immunosuppression are well recognized side-effects of cancer treatment, the underlying mechanisms including changes in the composition of gut microbiota and Clostridium difficile infection have not yet been thoroughly reviewed. We herein set out to review the literature regarding the relations between cancer chemotherapy, radiation treatment, and Clostridium difficile-associated colitis. Review of the English language literature published from 2008 to 2015 on the association between cancer chemotherapy, radiation treatment, and C. difficile-associated colitis. Certain chemotherapeutic combinations, mainly those containing paclitaxel, are more likely to be followed by C. difficile infection (CDI), while some tumor types are more likely to be complicated by CDI following chemotherapy. CDI following irradiation occurs mostly in patients who were treated for cancer in the head and neck area. Risk factors found were proton pump inhibitors, antibiotics, cytostatic agents, and tube feeding. The drug of choice for an initial episode of mild-to-moderate CDI is metronidazole, whereas vancomycin is reserved for an initial episode of severe CDI. Fidaxomycin is another option for treatment of severe CDI, with fewer recurrences. The influence of CDI on the treatment of oncological patients is not fully acknowledged. Infection with C. difficile is more frequent in those patients treated by antibiotics simultaneously with chemotherapy. Aggressive supportive care with intravenous hydration, antibiotics, and close surgical monitoring for selective intervention can significantly decrease the morbidity and life-threatening complications associated with this infection.

A novel multi-drug metronomic chemotherapy significantly delays tumor growth in mice.

PubMed

Tagliamonte, Maria; Petrizzo, Annacarmen; Napolitano, Maria; Luciano, Antonio; Rea, Domenica; Barbieri, Antonio; Arra, Claudio; Maiolino, Piera; Tornesello, Marialina; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

2016-02-24

The tumor immunosuppressive microenvironment represents a major obstacle to an effective tumor-specific cellular immune response. In the present study, the counterbalance effect of a novel metronomic chemotherapy protocol on such an immunosuppressive microenvironment was evaluated in a mouse model upon sub-cutaneous ectopic implantation of B16 melanoma cells. The chemotherapy consisted of a novel multi-drug cocktail including taxanes and alkylating agents, administered in a daily metronomic fashion. The newly designed strategy was shown to be safe, well tolerated and significantly efficacious. Treated animals showed a remarkable delay in tumor growth and prolonged survival as compared to control group. Such an effect was directly correlated with CD4(+) T cell reduction and CD8(+) T cell increase. Furthermore, a significant reduction in the percentage of both CD25(+)FoxP3(+) and CD25(+)CD127(low) regulatory T cell population was found both in the spleens and in the tumor lesions. Finally, the metronomic chemotherapy induced an intrinsic CD8(+) T cell response specific to B16 naturally expressed Trp2 TAA. The novel multi-drug daily metronomic chemotherapy evaluated in the present study was very effective in counterbalancing the immunosuppressive tumor microenvironment. Consequently, the intrinsic anti-tumor T cell immunity could exert its function, targeting specific TAA and significantly containing tumor growth. Overall, the results show that this represents a promising adjuvant approach to significantly enhance efficacy of intrinsic or vaccine-elicited tumor-specific cellular immunity.

Alkylating chemotherapy may exert a uniquely deleterious effect upon neo-antigen-targeting anticancer vaccination

PubMed Central

Litterman, Adam J; Dudek, Arkadiusz Z; Largaespada, David A

2013-01-01

Alkylating chemotherapy exerts both antineoplastic and immunostimulatory effects. However, in addition to depleting regulatory T cells (Treg), alkylating agents also mediate a long lasting antiproliferative effect on responder lymphocytes. Our recent findings indicate that this antiproliferative effect profoundly impairs vaccination-induced immune responses, especially in the case of vaccines that target specific tumor-associated neo-antigens that do not require Treg depletion. PMID:24251080

Exercise and chemotherapy-induced amenorrhea.

PubMed

Mathis, Katlynn M; Sturgeon, Kathleen M; Winkels, Renate M; Wiskemann, Joachim; Williams, Nancy I; Schmitz, Kathryn

2018-07-01

Chemotherapy-induced amenorrhea (CIA) is the temporary or permanent loss of menses experienced by premenopausal women undergoing chemotherapy treatment for cancer. Two possible mechanisms through which chemotherapy induces CIA have been identified: systemic endothelial dysfunction, resulting in decreased blood flow to the ovaries, and increased oxidative stress within the ovaries, both of which are proposed to lead to apoptosis of follicles. Endothelial dysfunction in ovarian arteries in women undergoing or who have undergone chemotherapy treatment is characterized by prothrombotic changes and thickening of the vascular wall. These changes result in occlusion of the blood vessels. Oxidative stress is increased and antioxidants decreased in the ovaries secondary to chemotherapy drugs, specifically cyclophosphamide. It is hypothesized that low to moderate intensity aerobic exercise during chemotherapy may prevent these changes and lessen the risk for developing CIA in premenopausal women. Low to moderate intensity aerobic exercise has been shown to improve endothelial function and blood flow in patients with cardiovascular disease-a disease state characterized by endothelial dysfunction and for which patients who have undergone chemotherapy are at increased risk. In mice, moderate intensity aerobic exercise has been shown to decrease the amount of oxidative stress within the ovaries, and in humans, chronic aerobic exercise has been shown to increase antioxidant production systemically. This hypothesis should be tested in both a mouse model, using sedentary and exercising mice treated with chemotherapy drugs that commonly result in CIA, as well as a human model to determine the effects of low to moderate intensity aerobic exercise on ovarian function in premenopausal women undergoing chemotherapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Customizing chemotherapy for colon cancer: the potential of gene expression profiling.

PubMed

Mariadason, John M; Arango, Diego; Augenlicht, Leonard H

2004-06-01

The value of gene expression profiling, or microarray analysis, for the classification and prognosis of multiple forms of cancer is now clearly established. For colon cancer, expression profiling can readily discriminate between normal and tumor tissue, and to some extent between tumors of different histopathological stage and prognosis. While a definitive in vivo study demonstrating the potential of this methodology for predicting response to chemotherapy is presently lacking, the ability of microarrays to distinguish other subtleties of colon cancer phenotype, as well as recent in vitro proof-of-principle experiments utilizing colon cancer cell lines, illustrate the potential of this methodology for predicting the probability of response to specific chemotherapeutic agents. This review discusses some of the recent advances in the use of microarray analysis for understanding and distinguishing colon cancer subtypes, and attempts to identify challenges that need to be overcome in order to achieve the goal of using gene expression profiling for customizing chemotherapy in colon cancer.

The effect of interstitial pressure on therapeutic agent transport: coupling with the tumor blood and lymphatic vascular systems.

PubMed

Wu, Min; Frieboes, Hermann B; Chaplain, Mark A J; McDougall, Steven R; Cristini, Vittorio; Lowengrub, John S

2014-08-21

Vascularized tumor growth is characterized by both abnormal interstitial fluid flow and the associated interstitial fluid pressure (IFP). Here, we study the effect that these conditions have on the transport of therapeutic agents during chemotherapy. We apply our recently developed vascular tumor growth model which couples a continuous growth component with a discrete angiogenesis model to show that hypertensive IFP is a physical barrier that may hinder vascular extravasation of agents through transvascular fluid flux convection, which drives the agents away from the tumor. This result is consistent with previous work using simpler models without blood flow or lymphatic drainage. We consider the vascular/interstitial/lymphatic fluid dynamics to show that tumors with larger lymphatic resistance increase the agent concentration more rapidly while also experiencing faster washout. In contrast, tumors with smaller lymphatic resistance accumulate less agents but are able to retain them for a longer time. The agent availability (area-under-the curve, or AUC) increases for less permeable agents as lymphatic resistance increases, and correspondingly decreases for more permeable agents. We also investigate the effect of vascular pathologies on agent transport. We show that elevated vascular hydraulic conductivity contributes to the highest AUC when the agent is less permeable, but to lower AUC when the agent is more permeable. We find that elevated interstitial hydraulic conductivity contributes to low AUC in general regardless of the transvascular agent transport capability. We also couple the agent transport with the tumor dynamics to simulate chemotherapy with the same vascularized tumor under different vascular pathologies. We show that tumors with an elevated interstitial hydraulic conductivity alone require the strongest dosage to shrink. We further show that tumors with elevated vascular hydraulic conductivity are more hypoxic during therapy and that the response

Chemotherapy drug extravasation in totally implantable venous access port systems: how effective is early surgical lavage?

PubMed

Azaïs, Henri; Bresson, Lucie; Bassil, Alfred; Katdare, Ninad; Merlot, Benjamin; Houpeau, Jean-Louis; El Bedoui, Sophie; Meurant, Jean-Pierre; Tresch, Emmanuelle; Narducci, Fabrice

2015-01-01

Totally implantable venous access port systems (TIVAPS) are a widely used and an essential tool in the efficient delivery of chemotherapy. Chemotherapy drug extravasation (CDE) can have dire consequences and will delay treatment. The purpose of this study is to both clarify the management of CDE and show the effectiveness of early surgical lavage (ESL). Patients who had presented to the Cancer Center of Lille (France) with TIVAPS inserted between January 2004 and April 2013 and CDE had their medical records reviewed retrospectively. Thirty patients and 33 events were analyzed. Implicated agents were vesicants (51.5%), irritants (45.5%) and non-vesicants (3%). Huber needle malpositionning was involved in 27 cases. Surgery was performed in 97% of cases, 87.5% of which were for ESL with 53.1% of the latter requiring TIVAPS extraction. Six patients required a second intervention due to adverse outcomes (severe cases). Vesicants were found to be implicated in four out of six severe cases and oxaliplatin in two others. Extravasated volume was above 50 ml in 80% of cases. Only one patient required a skin graft. CDEs should be managed in specialized centers. ESL allows for limited tissue contact of the chemotherapy drug whilst using a simple, widely accessible technique. The two main factors that correlate with adverse outcome seem to be the nature of the implicated agent (vesicants) and the extravasated volume (above 50 ml) leading to worse outcomes. Oxaliplatin should be considered as a vesicant.

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

PubMed

Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

2005-12-15

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

Burden of Chemotherapy-Induced Febrile Neutropenia Hospitalizations in US Clinical Practice, by Use and Patterns of Prophylaxis with Colony-Stimulating Factor.

PubMed

Weycker, Derek; Li, Xiaoyan; Tzivelekis, Spiros; Atwood, Mark; Garcia, Jacob; Li, Yanli; Reiner, Maureen; Lyman, Gary H

2017-02-01

Evidence suggests that many cancer chemotherapy patients who are candidates for colony-stimulating factor (CSF) prophylaxis do not receive it or receive it inconsistent with guidelines, and that such patients have a higher risk of febrile neutropenia hospitalization (FNH). Little is known about the number and consequences of FNH by use/patterns of CSF prophylaxis in US clinical practice. A retrospective cohort design and private healthcare claims data were employed. Study population comprised adults who received a chemotherapy course with a high-risk regimen, or an intermediate-risk regimen (if ≥1 FN risk factor present), for non-metastatic breast cancer or non-Hodgkin's lymphoma (NHL); each chemotherapy cycle within the course and each FNH episode within the cycles were identified. Consequences included mortality, inpatient days, and costs (US$2013) during FNH. Use (yes/no) and patterns (agent, administration day/duration) of CSF prophylaxis were evaluated within cycles in which FNH episodes occurred. Among all FNH episodes (n=6,355; 109 episodes per 1,000 patients), 41.3% (95% CI: 40.1-42.5) occurred among patients who did not receive CSF prophylaxis in that cycle, and 8.8% (8.1-9.5) occurred among those who received CSF prophylaxis on the same day as chemotherapy. Among FNH episodes occurring in patients who received daily CSF agents (2% of CSF use), 56.1% (44.1-68.0) received prophylaxis <7 days during the cycle. Results for FNH consequences were comparable. In this retrospective evaluation, one-half of FNH episodes, outcomes, and costs among cancer chemotherapy patients who were candidates for CSF prophylaxis occurred in those who either did not receive it or received it inconsistent with guidelines.

Practice Patterns in Hepatitis B Virus Screening Before Cancer Chemotherapy in a Major US Hospital Network.

PubMed

Kwak, Ye Eun; Stein, Stacy M; Lim, Joseph K

2018-01-01

Cancer patients receiving chemotherapy face an increased risk of reactivation of chronic hepatitis B virus infection. To determine the HBV screening rate in patients receiving cancer chemotherapy in various clinical settings. We identified 11,959 adult cancer patients (age ≥ 18 years) receiving parenteral chemotherapy between 2012 and 2015 within a major US hospital network, including a large university hospital, community teaching hospitals, and community oncology clinics. Two thousand and forty-five patients (17.1%) were screened for either HBV surface antigen (HBsAg) or HBV core antibody (HBcAb) before chemotherapy, and 1850 patients (15.5%) had both HBsAg and HBcAb tested before chemotherapy. 8.4% were exposed to HBV, and 0.9% had chronic HBV infection (both HBsAg/HBcAb positive). Patients with hematologic tumor were more often screened than with solid tumor (55.6 vs. 8.3%, p < 0.001). Patients receiving chemotherapy with higher HBV reactivation risk had higher yet suboptimal HBV screening rate (41.1% B-depleting agents, 21.5% anthracycline, 14.9% steroid, 64.7% anti-TNF alpha and 18.6% other chemotherapy, p < 0.001). Patients with age ≥ 50 years (old 16.2% vs. young 23.9%, p < 0.001) and Asian ethnicity (Asian 13.6 vs. Caucasian 16.6%, p < 0.001) were screened less for HBV despite higher prevalence of HBV exposure (old 9.3% vs. young 4.3%, p < 0.001 and Asian 27.8% vs. Caucasian 6.4%, p < 0.001). Patients receiving chemotherapy in community oncology clinics were less screened versus community teaching hospitals or university hospital (12.7 vs. 19.1 vs. 19.7%, p < 0.001), despite similar prevalence of HBV infection. On multivariate analysis, receiving chemotherapy at a community oncology clinic [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.45-0.72, p < 0.001] was independently associated with less HBV screening compared to receiving chemotherapy at a university or community teaching hospital. HBV screening among patients

[Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

PubMed

Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

2004-06-01

To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

Successful treatment of natural killer (NK) cell leukemia following a long-standing chronic active Epstein-Barr virus (CAEBV) infection with allogeneic bone marrow transplantation.

PubMed

Ebihara, Y; Manabe, A; Tanaka, R; Yoshimasu, T; Ishikawa, K; Iseki, T; Hayakawa, J; Maeda, M; Asano, S; Tsuji, K

2003-06-01

The optimal treatment for natural killer (NK) cell leukemia after chronic active Epstein-Barr virus (CAEBV) infection has not been determined. A 15-year-old boy presented with NK cell leukemia following CAEBV infection for 5 years. The peripheral blood and BM had an increased number of CD3(-)CD56(+) large granular lymphocytes and a monoclonal integration of the EBV genome was detected. Chemotherapy was not sufficiently effective to control the disease. Allogeneic BMT from an HLA-identical sister was performed using a conditioning regimen consisting of total body irradiation, cyclophosphamide and thiotepa. The patient is disease-free with a perfect performance status 24 months after BMT. This is the first report to show that allogeneic BMT is potentially able to cure NK cell leukemia after CAEBV infection.

Chemotherapy to Treat Cancer

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.

The continuing search for antitumor agents from higher plants

PubMed Central

Pan, Li; Chai, Heebyung; Kinghorn, A. Douglas

2009-01-01

Plant secondary metabolites and their semi-synthetic derivatives continue to play an important role in anticancer drug therapy. In this short review, selected single chemical entity antineoplastic agents from higher plants that are currently in clinical trials as cancer chemotherapy drug candidates are described. These compounds are representative of a wide structural diversity. In addition, the approaches taken toward the discovery of anticancer agents from tropical plants in the laboratory of the authors are summarized. The successful clinical utilization of cancer chemotherapeutic agents from higher plants has been evident for about half a century, and, when considered with the promising pipeline of new plant-derived compounds now in clinical trials, this augurs well for the continuation of drug discovery research efforts to elucidate additional candidate substances of this type. PMID:20228943

Filling in the gaps: reporting of concurrent supportive care therapies in breast cancer chemotherapy trials.

PubMed

Freedman, Orit; Amir, Eitan; Zimmermann, Camilla; Clemons, Mark

2011-03-01

Supportive care interventions can have a substantial impact on side effects of chemotherapy. Consequently, accurate reporting of such interventions is essential when interpreting clinical trial results. This study determined the prevalence and quality of reporting of supportive care treatment for common chemotherapy-induced toxicities in phase III, breast cancer chemotherapy trials. A systematic review of phase III trials of breast cancer trials incorporating chemotherapy published in the last 5 years was undertaken. Trials were identified through MEDLINE, EMBASE, BIOSIS, and the Cochrane Library. Supportive treatments evaluated were use of antiemetics, colony-stimulating growth factors, and antibiotics. Reporting quality was rated as "good", "fair", "poor", or "absent" using predetermined criteria. Sixty-two trials met inclusion criteria. In 41 studies (66%), details regarding prophylactic antiemetic treatment were not provided. Growth factor use was not reported in 20 trials (32%). Instructions for the use of prophylactic antibiotics were absent in 45 trials (72%). There are significant deficiencies in reporting of use of prophylactic supportive care agents in breast cancer trials. Omission of supportive care instructions may impact substantially on patient management and health care system expenditure. Recommendations for the type, dose, and frequency of supportive care drugs should be provided and reported on in trials.

An analysis of the therapeutic benefits of genotyping in pediatric hematopoietic stem cell transplantation.

PubMed

Wright, Felicity A; Bebawy, Mary; O'Brien, Tracey A

2015-01-01

Hematopoietic stem cell transplantation is a high-risk procedure that is offered, with curative intent, to patients with malignant and nonmalignant disease. The clinical benefits of personalization of therapy by genotyping have been demonstrated by the reduction in transplant related mortality from donor-recipient HLA matching. However, defining the relationship between genotype and transplant conditioning agents is yet to be translated into clinical practice. A number of the therapeutic agents used in stem cell transplant preparative regimens have pharmacokinetic parameters that predict benefit of incorporating pharmacogenomic data into dosing strategies. Busulfan, cyclophosphamide, thio-TEPA and etoposide have well-described drug metabolism pathways, however candidate gene studies have identified there is a gap in the identification of pharmacogenomic data that can be used to improve transplant outcomes. Incorporating pharmacogenomics into pharmacokinetic modeling may demonstrate the therapeutic benefits of genotyping in transplant preparative regimen agents.

Association of cytochrome P450 genetic polymorphisms with neoadjuvant chemotherapy efficacy in breast cancer patients

PubMed Central

2012-01-01

Background The enzymes of the cytochrome P450 family (CYPs) play an important role in the metabolism of a great variety of anticancer agents; therefore, polymorphisms in genes encoding for metabolizing enzymes and drugs transporters can affect drug efficacy and toxicity. Methods The genetic polymorphisms of cytochrome P450 were studied in 395 patients with breast cancer by RLFP analysis. Results Here, we studied the association of functionally significant variant alleles of CYP3A4, CYP3A5, CYP2B6, CYP2C8, CYP2C9 and CYP2C19 with the clinical response to neoadjuvant chemotherapy in breast cancer patients. A significant correlation was observed between the CYP2C9*2 polymorphism and chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91), as well as between CYP2C9*2 heterozygotes and chemotherapy resistance in women with nodal forms of breast cancer and a cancer hereditary load (OR = 15.50; CI 95% = 1.08 – 826.12) when the potential combined effects were examined. No significant association between chemotherapy resistance and the other examined genotypes and the potential combined clinical and tumour-related parameters were discovered. Conclusion In conclusion, CYP2C9*2 was associated with neoadjuvant chemotherapy resistance (OR = 4.64; CI 95% = 1.01 – 20.91) in the population of interest. PMID:22702493

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

PubMed

Fornaro, Lorenzo; Vivaldi, Caterina; Cereda, Stefano; Leone, Francesco; Aprile, Giuseppe; Lonardi, Sara; Silvestris, Nicola; Santini, Daniele; Milella, Michele; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Falcone, Alfredo; Brandi, Giovanni; Sperduti, Isabella; Vasile, Enrico

2015-12-23

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

PubMed Central

Liang, Wenjie; Ni, Yicheng; Chen, Feng

2016-01-01

The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

Chemotherapy changes cytotoxic activity of NK-cells in cancer patients

NASA Astrophysics Data System (ADS)

Stakheyeva, M.; Yunusova, N.; Patysheva, M.; Mitrofanova, I. V.; Faltin, V.; Tuzikov, S.; Slonimskaya, E.

2017-09-01

In recent years, it has been shown that under certain conditions cytostatic agents (chemotherapy and radiotherapy) can restore the functioning of the immune system impaired by malignancy burden. The modifications of biological properties by cytostatics acting make cancer cells visible for the immune system recognition and elimination. Eighteen patients diagnosed with primary local breast (8) and gastric (10) cancer between 2014 and 2016 were enrolled in the investigation. The phenotypic features of NK were assessed by flow cytometry using mAb (BD Pharmingen) against CD45 (common leukocyte antigen) and CD56 (NK-marker) for surface staining, CD107a (LAMP-1), Perforin (PF) and Gransime B (GB) for intracellular staining. We examined NK populations in the peripheral blood of cancer patients before treatment and in 5 days after second course of NACT. We found that NK populations produced PF in cancer patents, which were absent before treatment, increased after NACT. Their emergence can be associated with the immunoactivating effects of chemotherapy, realized by the modification of tumor cells or elimination of immunosuppressive cells.

Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression.

PubMed

Bisi, John E; Sorrentino, Jessica A; Roberts, Patrick J; Tavares, Francis X; Strum, Jay C

2016-05-01

Chemotherapy-induced myelosuppression continues to represent the major dose-limiting toxicity of cytotoxic chemotherapy, which can be manifested as neutropenia, lymphopenia, anemia, and thrombocytopenia. As such, myelosuppression is the source of many of the adverse side effects of cancer treatment including infection, sepsis, bleeding, and fatigue, thus resulting in the need for hospitalizations, hematopoietic growth factor support, and transfusions (red blood cells and/or platelets). Moreover, clinical concerns raised by myelosuppression commonly lead to chemotherapy dose reductions, therefore limiting therapeutic dose intensity, and reducing the antitumor effectiveness of the treatment. Currently, the only course of treatment for myelosuppression is growth factor support which is suboptimal. These treatments are lineage specific, do not protect the bone marrow from the chemotherapy-inducing cytotoxic effects, and the safety and toxicity of each agent is extremely specific. Here, we describe the preclinical development of G1T28, a novel potent and selective CDK4/6 inhibitor that transiently and reversibly regulates the proliferation of murine and canine bone marrow hematopoietic stem and progenitor cells and provides multilineage protection from the hematologic toxicity of chemotherapy. Furthermore, G1T28 does not decrease the efficacy of cytotoxic chemotherapy on RB1-deficient tumors. G1T28 is currently in clinical development for the reduction of chemotherapy-induced myelosuppression in first- and second-line treatment of small-cell lung cancer. Mol Cancer Ther; 15(5); 783-93. ©2016 AACR. ©2016 American Association for Cancer Research.

Chemotherapy-induced anemia and oncologist perception on treatment: results of a web-based survey.

PubMed

Cortinovis, Diego; Beretta, Giordano; Piazza, Elena; Luchena, Giovanna; Aglione, Stefania; Bertolini, Alessandro; Buzzoni, Roberto; Cabiddu, Mary; Carnaghi, Carlo; Danova, Marco; Farina, Gabriella; Ferrari, Vittorio; Frascaroli, Mara; Reni, Michele; Tansini, Giuseppe

2013-01-01

Anemia prevalence and incidence in chemotherapy-treated patients is high. Erythropoiesis-stimulating agents (ESAs) are frequently employed in the management of chemotherapy-induced anemia. However, other treatments such as red blood transfusion or iron supplementation are normally used. Recent international guidelines raised some concern about ESAs employment with a possible impact in chemotherapy-induced anemia management and changes in clinical practice behavior. To evaluate opinions about chemotherapy-induced anemia clinical management preference, the Associazione Italiana Oncologia Medica (AIOM) Lombardy section coordinators sent via email a 12-item questionnaire about their knowledge on CIA and usual therapeutic strategies to manage this adverse event to AIOM Lombardy onco-hematologist members. From January 2011 to March 2011, 81 questionnaires were collected with an approximated share of 30%. The survey was completed mainly by oncologists (91%) aged 35-50 years (50%). Chemotherapy-induced anemia was considered to have clinical impact in changing cancer therapeutic strategy by nearly 60% of the respondents. ESAs were administered largely (80%) with concomitant iron supplementation in 52%; 38% jointly used blood transfusion as part of the therapy. Nearly 20% of those who replied correctly employed transferrin saturation levels as a marker to guide iron supplementation. Physician prescribers strictly followed the guidelines to start and stop ESAs even if 14% were negatively influenced by new ASCO recommendations. ESA biosimilars were considered future substitutes of originators in 45% of the cases. Chemotherapy-induced anemia was perceived as an adverse event with a mild impact on clinical practice. ESAs were largely employed, however the number of transfusions and lack of employment of markers of iron depletion suggested that adherence to guidelines could be theoretically met but with some discordances regarding the most appropriate strategies in daily clinical

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study

PubMed Central

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-01-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. PMID:25533447

Outcome after reduced chemotherapy for intermediate-risk neuroblastoma.

PubMed

Baker, David L; Schmidt, Mary L; Cohn, Susan L; Maris, John M; London, Wendy B; Buxton, Allen; Stram, Daniel; Castleberry, Robert P; Shimada, Hiroyuki; Sandler, Anthony; Shamberger, Robert C; Look, A Thomas; Reynolds, C Patrick; Seeger, Robert C; Matthay, Katherine K

2010-09-30

among patients with intermediate-risk neuroblastoma was achieved with a biologically based treatment assignment involving a substantially reduced duration of chemotherapy and reduced doses of chemotherapeutic agents as compared with the regimens used in earlier trials. These data provide support for further reduction in chemotherapy with more refined risk stratification. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00003093.)

Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer.

PubMed

Jaaback, Kenneth; Johnson, Nick; Lawrie, Theresa A

2011-11-09

Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010 and May 2011. In addition, we handsearched and cascade searched the major gynaecological oncology journals. The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0

Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer

PubMed Central

Jaaback, Kenneth; Johnson, Nick; Lawrie, Theresa A

2014-01-01

Background Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. Objectives To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. Search methods We searched the Gynaecological Cancer Review Group’s Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010 and May 2011. In addition, we handsearched and cascade searched the major gynaecological oncology journals. Selection criteria The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. Data collection and analysis We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. Main results Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less

Guided molecular missiles for tumor-targeting chemotherapy--case studies using the second-generation taxoids as warheads.

PubMed

Ojima, Iwao

2008-01-01

A long-standing problem in cancer chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Therefore, the development of innovative and efficacious tumor-specific drug delivery protocols or systems is urgently needed. A rapidly growing tumor requires various nutrients and vitamins. Thus, tumor cells overexpress many tumor-specific receptors, which can be used as targets to deliver cytotoxic agents into tumors. This Account presents our research program on the discovery and development of novel and efficient drug delivery systems, possessing tumor-targeting ability and efficacy against various cancer types, especially multidrug-resistant tumors. In general, a tumor-targeting drug delivery system consists of a tumor recognition moiety and a cytotoxic warhead connected directly or through a suitable linker to form a conjugate. The conjugate, which can be regarded as a "guided molecular missile", should be systemically nontoxic, that is, the linker must be stable in blood circulation, but upon internalization into the cancer cell, the conjugate should be readily cleaved to regenerate the active cytotoxic warhead. These novel "guided molecular missiles" are conjugates of the highly potent second-generation taxoid anticancer agents with tumor-targeting molecules through mechanism-based cleavable linkers. These conjugates are specifically delivered to tumors and internalized into tumor cells, and the potent taxoid anticancer agents are released from the linker into the cytoplasm. We have successfully used omega-3 polyunsaturated fatty acids, in particular DHA, and monoclonal antibodies (for EGFR) as tumor-targeting molecules for the conjugates, which exhibited remarkable efficacy against

Successful treatment of ovarian cancer with apatinib combined with chemotherapy

PubMed Central

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-01-01

Abstract Rationale: The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. Patients concerns: A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Diagnosis: Ovarian cancer. Interventions: The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand–foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. Outcomes: The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Lessons: Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially

Impact of Neoadjuvant Chemotherapy on Breast Reconstruction

PubMed Central

Hu, Yue-Yung; Weeks, Christine M.; In, Haejin; Dodgion, Christopher M.; Golshan, Mehra; Chun, Yoon S.; Hassett, Michael J.; Corso, Katherine A.; Gu, Xiangmei; Lipsitz, Stuart R.; Greenberg, Caprice C.

2011-01-01

BACKGROUND With advances in oncologic treatment, cosmesis after mastectomy has assumed a pivotal role in patient and provider decision making. Multiple studies have confirmed the safety of both chemotherapy before breast surgery and immediate reconstruction. Little has been written about the effect of neoadjuvant chemotherapy on decisions about reconstruction. METHODS The authors identified 665 patients with stage I through III breast cancer who received chemotherapy and underwent mastectomy at Dana-Farber/Brigham & Women’s Cancer Center from 1997 to 2007. By using multivariate logistic regression, reconstruction rates were compared between patients who received neoadjuvant chemotherapy (n = 180) and patients who underwent mastectomy before chemotherapy (n = 485). The rate of postoperative complications after mastectomy was determined for patients who received neoadjuvant chemotherapy compared with those who did not. RESULTS Reconstruction was performed immediately in 44% of patients who did not receive neoadjuvant chemotherapy but in only 23% of those who did. Twenty-one percent of neoadjuvant chemotherapy recipients and 14% of adjuvant-only chemotherapy recipients underwent delayed reconstruction. After controlling for age, receipt of radiotherapy, and disease stage, neoadjuvant recipients were less likely to undergo immediate reconstruction (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.37, 0.87) but were no more likely to undergo delayed reconstruction (OR, 1.29; 95% CI, 0.75, 2.20). Surgical complications occurred in 30% of neoadjuvant chemotherapy recipients and in 31% of adjuvant chemotherapy recipients. CONCLUSIONS The current results suggest that patients who receive neoadjuvant chemotherapy are less likely to undergo immediate reconstruction and are no more likely to undergo delayed reconstruction than patients who undergo surgery before they receive chemotherapy. PMID:21264833

Desensitization for Drug Hypersensitivity to Chemotherapy and Monoclonal Antibodies.

PubMed

Bonamichi-Santos, Rafael; Castells, Mariana

2016-01-01

Chemotherapies drugs and monoclonal antibodies are key components of the treatment of cancer patients and patients with chronic inflammatory conditions to provide increase in life expectancy and quality of life. Their increased use has lead to an increase in drugs hypersensitivity reactions (DHR) worldwide. DHR to those agents prevented their use and promoted the use of second line therapies to protect patients' hypersensitive reactions and anaphylaxis. Second line medications may not fully address the patients' medical condition and it is desirable to keep patients on first line therapy. Drug hypersensitivity symptoms can range from mild cutaneous reactions to life-threatening anaphylaxis. Rapid drug desensitization (RDD) is a novel approach to the management of drug hypersensitivity reactions which are IgE and non-IgE mediated. Through the diferent desensitization protocols patients can receive the full dose of the medications that they have presented a hypersensitive reaction and been protected against anaphylaxis. This review looks at the current literature on hypersensitivity reactions (HSR) to chemotherapy drugs and monoclonal antibodies and the potential use of RDD for their management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model.

PubMed

Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

2014-01-01

Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. This study compared the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6-12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients.

Kanglaite injection plus chemotherapy versus chemotherapy alone for non-small cell lung cancer patients: A systematic review and meta-analysis.

PubMed

Liu, Xuemei; Xu, Feng; Wang, Gang; Diao, Xiang; Li, Youping

2008-10-01

Kanglaite (KLT) is a botanically sourced, molecularly targeted agent that is prepared as a microemulsion for IV use. The active substance is extracted from the herb Semen coicis. The aim of this study was to evaluate the effectiveness and tolerability of KLT injection in patients with primary non-small cell lung cancer (NSCLC). We electronically searched the literature of the China National Knowledge Infrastructure (Chinese language, 1979-March 2008), CBMdisc (Chinese, 1978-March 2008), The Cochrane Library (English, Issue 4, 2007), MEDLINE (English, 1966-March 2008), and EMBASE (English, 1984-March 2008), and manually searched 20 Chinese-language oncology journals to identify randomized controlled trials (RCTs) of KLT injection plus chemotherapy versus chemotherapy alone, regardless of their having been published or not, blinding, duration of treatment, or duration of follow-up. The quality of the included trials was assessed using the method recommended by The Cochrane Collaboration. The studies were assigned to 1 of the following 3 categories: A = all quality criteria met, low risk of bias; B = ≥1 of the quality criteria only partially met, moderate risk of bias; or C = ≥1 of the quality criteria not met, high risk of bias. If heterogeneity existed among subgroups, then overall results were calculated based on a random-effects model; otherwise, a fixed-effects model was used. Electronic database searches yielded 596 citations. A title review eliminated 377 manuscripts; 219 citations were marked for further evaluation. Finally, we identified 26 trials that met the inclusion and exclusion criteria. The 26 RCTs included in this meta-analysis included 2209 patients with NSCLC; no study was graded A, 9 were graded B, and 17 were graded C. The sample size of each trial varied from 40 to 305 patients; none of the trials had precalculated sample sizes. Pooled analyses performed using both fixed- and random-effects models revealed that compared with chemotherapy

Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source.

PubMed

Ma, Jiacheng; Kavelaars, Annemieke; Dougherty, Patrick M; Heijnen, Cobi J

2018-06-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of many chemotherapeutic agents, affecting >60% of patients with cancer. Moreover, CIPN persists long into survivorship in approximately 20% to 30% of these patients. To the authors' knowledge, no drugs have been approved to date by the US Food and Drug Administration to effectively manage chemotherapy-induced neuropathic pain. The majority of the drugs tested for the management of CIPN aim at symptom relief, including pain and paresthesia, yet are not very efficacious. The authors propose that there is a need to acquire a more thorough understanding of the etiology of CIPN so that effective, mechanism-based, disease-modifying interventions can be developed. It is important to note that such interventions should not interfere with the antitumor effects of chemotherapy. Mitochondria are rod-shaped cellular organelles that represent the powerhouses of the cell, in that they convert oxygen and nutrients into the cellular energy "currency" adenosine triphosphate. In addition, mitochondria regulate cell death. Neuronal mitochondrial dysfunction and the associated nitro-oxidative stress represent crucial final common pathways of CIPN. Herein, the authors discuss the potential to prevent or reverse CIPN by protecting mitochondria and/or inhibiting nitro-oxidative stress with novel potential drugs, including the mitochondrial protectant pifithrin-μ, histone deacetylase 6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and anti-inflammatory mediators including interleukin 10. This review hopefully will contribute toward bridging the gap between preclinical research and the development of realistic novel therapeutic strategies to prevent or reverse the devastating neurotoxic effects of chemotherapy on the (peripheral) nervous system. Cancer 2018;124:2289-98. © 2018 American Cancer Society. © 2018 American Cancer Society.

Advances in drug delivery system for platinum agents based combination therapy.

PubMed

Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

2015-12-01

Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.

Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review.

PubMed

Jimmy, Rincy; Stern, Cindy; Lisy, Karolina; White, Sarahlouise

2017-08-01

Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy. Therefore, there is a critical need for more effective and innovative therapeutic approaches such as immune stimulatory agents. The most extensively studied immune stimulatory agent in the treatment of osteosarcoma is mifamurtide. The aim of this systematic review was to identify and synthesize the evidence on the effectiveness of mifamurtide in addition to standard chemotherapy on survival outcomes. To present the best available evidence on the treatment of high-grade non-metastatic and metastatic osteosarcoma with mifamurtide in addition to standard chemotherapy. All populations of patients regardless of age, gender or ethnicity with high-grade, resectable, non-metastatic and metastatic osteosarcoma based on histological diagnosis. This review focused on intravenous infusion of either of the pharmaceutical formulations of mifamurtide (MTP-PE or L-MTP-PE) in addition to standard chemotherapy, and the comparator was chemotherapy alone. This review considered any experimental study design including randomized controlled trials, non-randomized trials and quasi-experimental studies. The primary outcomes of interest were event-free survival, overall survival and recurrence of osteosarcoma. Secondary outcomes that were considered included health-related quality of life and any mifamurtide-related adverse events. A search for published and unpublished literature in English was undertaken (seven published literature databases, four unpublished literature

Sensitizing basal-like breast cancer to chemotherapy using nanoparticles conjugated with interference peptide

NASA Astrophysics Data System (ADS)

Sorolla, A.; Ho, D.; Wang, E.; Evans, C. W.; Ormonde, C. F. G.; Rashwan, R.; Singh, R.; Iyer, K. Swaminathan; Blancafort, P.

2016-04-01

Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary epithelial cell line. Furthermore, we show that treatment with EN1-iPep results in a highly synergistic pharmacological interaction with docetaxel in inhibiting cancer cell growth. The incorporation of these two agents in a single nanoformulation results in greater anticancer efficacy than current nanoparticle-based treatments used in the clinical setting.Basal-like breast cancers are highly aggressive malignancies associated with very poor prognosis. Although these cancers may initially respond to first-line treatment, they become highly resistant to standard chemotherapy in the metastatic setting. Chemotherapy resistance in basal-like breast cancers is associated with highly selective overexpression of the homeobox transcription factor Engrailed 1 (EN1). Herein, we propose a novel therapeutic strategy using poly(glycidyl methacrylate) nanoparticles decorated with poly(acrylic acid) that enable dual delivery of docetaxel and interference peptides designed to block or inhibit EN1 (EN1-iPep). We demonstrate that EN1-iPep is highly selective in inducing apoptotic cell death in basal-like cancer cells with negligible effects in a non-neoplastic human mammary

Ratiometric spectral imaging for fast tumor detection and chemotherapy monitoring in vivo

PubMed Central

Hwang, Jae Youn; Gross, Zeev; Gray, Harry B.; Medina-Kauwe, Lali K.; Farkas, Daniel L.

2011-01-01

We report a novel in vivo spectral imaging approach to cancer detection and chemotherapy assessment. We describe and characterize a ratiometric spectral imaging and analysis method and evaluate its performance for tumor detection and delineation by quantitatively monitoring the specific accumulation of targeted gallium corrole (HerGa) into HER2-positive (HER2 +) breast tumors. HerGa temporal accumulation in nude mice bearing HER2 + breast tumors was monitored comparatively by a. this new ratiometric imaging and analysis method; b. established (reflectance and fluorescence) spectral imaging; c. more commonly used fluorescence intensity imaging. We also tested the feasibility of HerGa imaging in vivo using the ratiometric spectral imaging method for tumor detection and delineation. Our results show that the new method not only provides better quantitative information than typical spectral imaging, but also better specificity than standard fluorescence intensity imaging, thus allowing enhanced in vivo outlining of tumors and dynamic, quantitative monitoring of targeted chemotherapy agent accumulation into them. PMID:21721808

Management of Breast Cancer Patients with Chemotherapy-Induced Neutropenia or Febrile Neutropenia

PubMed Central

Fontanella, Caterina; Bolzonello, Silvia; Lederer, Bianca; Aprile, Giuseppe

2014-01-01

Summary Chemotherapy-induced neutropenia (CIN) is a common toxicity caused by the administration of anticancer drugs. This side effect is associated with life-threatening infections and may alter the chemotherapy schedule, thus impacting on early and long-term outcomes. Elderly breast cancer patients with impaired health status or advanced disease as well as patients undergoing dose-dense anthracycline/taxane- or docetaxel-based regimens have the highest risk of CIN. A careful assessment of the baseline risk for CIN allows the selection of patients who need primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) and/or antimicrobial agents. Neutropenic cancer patients may develop febrile neutropenia and CIN-related severe medical complications. Specific risk assessment scores, along with comprehensive clinical evaluation, are able to define a group of febrile patients with low risk for complications who can be safely treated as outpatients. Conversely, patients with higher risk of severe complications should be hospitalized and should receive intravenous antibiotic therapy with or without G-CSF. PMID:25404882

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

PubMed

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-02-24

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

A Simple Method to Optimize the Effectiveness of Chemotherapy: Modulation of Glucose Intake During Chemotherapy.

PubMed

Icard, Philippe; Teboul, Bernard; El Baze, Philip

2017-11-01

Cancer cells consume high amounts of glucose to produce ATP and molecules entering biosynthesis. Numerous experimental studies have demonstrated that glucose deprivation and/or glycolysis inhibition arrest cancer cell growth and may increase the efficiency of cytotoxic drugs. In contrast, increasing glycolysis in tumor-infiltrating lymphocytes (TILs) activates these cells that destroy cancer cells. We propose to increase the efficiency of chemotherapy by modulating glucose intake during the course of chemotherapy. Glucose and caloric intake should be drastically reduced the day before and during chemotherapy administration to deprive cancer cells of ATP and molecules required to repair cytotoxic lesions. Few hours after chemotherapy, glucose and caloric intake should be drastically increased for few days to promote the activation of TILs that reinforce the destruction of cancer cells. This strategy could improve the results of chemotherapy by first enhancing cytotoxic stress against tumor cells and then promoting activation of the anti-cancer immune response. The modulation of glucose intake during chemotherapy should be tested clinically. The proposed scheme is simple, surely easier to follow than a strict chronic diet, and should avoid weight loss. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents.

PubMed

Katsuyama, Takayuki; Sada, Ken-Ei; Yan, Minglu; Zeggar, Sonia; Hiramatsu, Sumie; Miyawaki, Yoshia; Ohashi, Keiji; Morishita, Michiko; Watanabe, Haruki; Katsuyama, Eri; Takano-Narazaki, Mariko; Toyota-Tatebe, Noriko; Sunahori-Watanabe, Katsue; Kawabata, Tomoko; Miyake, Kohei; Kiguchi, Toru; Wada, Jun

2017-09-01

To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein-Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

PubMed

Tricco, Andrea C; Blondal, Erik; Veroniki, Areti Angeliki; Soobiah, Charlene; Vafaei, Afshin; Ivory, John; Strifler, Lisa; Cardoso, Roberta; Reynen, Emily; Nincic, Vera; Ashoor, Huda; Ho, Joanne; Ng, Carmen; Johnson, Christy; Lillie, Erin; Antony, Jesmin; Roberts, Derek J; Hemmelgarn, Brenda R; Straus, Sharon E

2016-12-23

Although serotonin (5-HT 3 ) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT 3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT 3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a

Simulating cancer growth with multiscale agent-based modeling.

PubMed

Wang, Zhihui; Butner, Joseph D; Kerketta, Romica; Cristini, Vittorio; Deisboeck, Thomas S

2015-02-01

There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simulating Cancer Growth with Multiscale Agent-Based Modeling

PubMed Central

Wang, Zhihui; Butner, Joseph D.; Kerketta, Romica; Cristini, Vittorio; Deisboeck, Thomas S.

2014-01-01

There have been many techniques developed in recent years to in silico model a variety of cancer behaviors. Agent-based modeling is a specific discrete-based hybrid modeling approach that allows simulating the role of diversity in cell populations as well as within each individual cell; it has therefore become a powerful modeling method widely used by computational cancer researchers. Many aspects of tumor morphology including phenotype-changing mutations, the adaptation to microenvironment, the process of angiogenesis, the influence of extracellular matrix, reactions to chemotherapy or surgical intervention, the effects of oxygen and nutrient availability, and metastasis and invasion of healthy tissues have been incorporated and investigated in agent-based models. In this review, we introduce some of the most recent agent-based models that have provided insight into the understanding of cancer growth and invasion, spanning multiple biological scales in time and space, and we further describe several experimentally testable hypotheses generated by those models. We also discuss some of the current challenges of multiscale agent-based cancer models. PMID:24793698

GnRH agonist leuprolide acetate does not confer any protection against ovarian damage induced by chemotherapy and radiation in vitro.

PubMed

Bildik, Gamze; Akin, Nazlı; Senbabaoglu, Filiz; Sahin, Gizem Nur; Karahuseyinoglu, Sercin; Ince, Umit; Taskiran, Cagatay; Selek, Ugur; Yakin, Kayhan; Guzel, Yilmaz; Ayhan, Cem; Alper, Ebru; Cetiner, Mustafa; Balaban, Basak; Mandel, Nil Molinas; Esen, Tarık; Iwase, Akira; Urman, Bulent; Oktem, Ozgur

2015-12-01

Is there any in vitro evidence for or against ovarian protection by co-administration of a GnRH agonist with chemotherapy in human? The co-administration of GnRH agonist leuprolide acetate with cytotoxic chemotherapy agents does not preserve ovarian reserve in vitro. Randomized controlled trials of the co-administration of gonadotrophin-releasing hormone (GnRH) agonists with adjuvant chemotherapy to preserve ovarian function have shown contradictory results. This fact, together with the lack of a proven molecular mechanism of action for ovarian protection with GnRH agonist (GnRHa) places this approach as a fertility preservation strategy under scrutiny. We therefore aimed in this study to provide in vitro evidence for or against the role of GnRHa in the prevention of chemotherapy-induced damage in human ovary. This translational research study of ex vivo and in vitro models of human ovary and granulosa cells was conducted in a university hospital between 2013 and 2015. Ovarian cortical pieces (n = 15, age 14-37) and mitotic non-luteinized (COV434 and HGrC1) and non-mitotic luteinized human granulosa cells (HLGC) expressing GnRH receptor were used for the experiments. The samples were treated with cyclophosphamide, cisplatin, paclitaxel, 5-FU, or TAC combination regimen (docetaxel, adriamycin and cyclophosphamide) with and without GnRHa leuprolide acetate for 24 h. DNA damage, apoptosis, follicle reserve, hormone markers of ovarian function and reserve (estradiol (E2), progesterone (P) and anti-mullerian hormone (AMH)) and the expression of anti-apoptotic genes (bcl-2, bcl-xL, bcl-2L2, Mcl-1, BIRC-2 and XIAP) were compared among control, chemotherapy and chemotherapy + GnRHa groups. The greatest magnitude of cytotoxicity was observed in the samples treated with cyclophosphamide, cisplatin and TAC regimen. Exposure to these drugs resulted in DNA damage, apoptosis and massive follicle loss along with a concurrent decline in the steroidogenic activity of the samples

Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation

PubMed Central

Moore, Caroline M.; Loizidou, Marilena; MacRobert, Alexander J.; Woodhams, Josephine H.

2016-01-01

Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI‐based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy. PMID:25758607

Is neoadjuvant chemotherapy prior to radio-chemotherapy beneficial in T4 anal carcinoma?

PubMed

Moureau-Zabotto, L; Viret, F; Giovaninni, M; Lelong, B; Bories, E; Delpero, J R; Pesenti, C; Caillol, F; de Chaisemartin, C; Minsat, M; Monges, G; Sarran, A; Resbeut, M

2011-07-01

This study retrospectively describes the outcome of a series of 38 patients (pts) with T4 anal carcinoma exclusively treated by radio and chemotherapy. From 1992 to 2007, 38 pts with UST4-N0-2-M0 anal carcinoma were treated with exclusive radiotherapy and chemotherapy. All patients received external beam radiotherapy (EBRT) (median dose 45 Gy) with a concomitant chemotherapy (5-fluorouracil-cisplatin). Eleven patients received neo-adjuvant chemotherapy (5-fluorouracil-cisplatin). After 2-8 weeks, a 15-20 Gy boost was delivered either with EBRT (20 pts) or interstitial (192)Ir brachytherapy (18 pts). Mean follow-up was 66 months. After chemoradiation therapy (CRT), 13 pts (34%) had a complete response, 23 pts (60%) a response >50% (2 pts were not evaluated). The 5-year-disease-free survival was 79.2 ± 6.5%, and the 5-year overall survival was 83.9 ± 6%. Eight patients developed tumor progression (mean delay 8.8 months), six of them requiring a salvage surgery with definitive colostomy for local relapse. Late severe complication requiring colostomy was observed in 2 pts. The 5-year-colostomy-free survival was 78 ± 6.9%. Patients who received primary chemotherapy had a statistically significant better 5-year colostomy-free survival (100% vs. 38 ± 16.4%, P = 0.0006). T4 anal carcinoma can be treated with a curative intent using a sphincter-sparing approach of CRT, and neo-adjuvant chemotherapy should be considered prior to radiotherapy. Copyright © 2011 Wiley-Liss, Inc.

Efficacy of Addition of Antiangiogenic Agents to Taxanes-Containing Chemotherapy in Advanced Nonsmall-Cell Lung Cancer

PubMed Central

Sheng, Jin; Yang, Yun-Peng; Yang, Bi-Jun; Zhao, Yuan-Yuan; Ma, Yu-Xiang; Hong, Shao-Dong; Zhang, Ya-Xiong; Zhao, Hong-Yun; Huang, Yan; Zhang, Li

2015-01-01

Abstract Preclinical researches indicated a potential synergistic effect of taxanes-containing chemotherapy (TCC) and antiangiogenic agents (AAs) on the treatment of advanced nonsmall-cell lung cancer (NSCLC). The advantage of adding AA to TCC in the real world remains confusing. We summarized the current evidences from relevant phase II/III randomized controlled trials (RCTs) by performing this meta-analyses. Electronic databases were searched for eligible literatures. The primary endpoint was overall survival (OS). Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were calculated using RevMan 5.2. A total of 14 phase II/III RCTs involving 9703 participants were included. Compared to standard TCC, the addition of AA was associated with the significant better OS (HR 0.92, 95% CI 0.87–0.97, P = 0.002), prolonged progression-free survival (HR 0.79, 95% CI 0.71–0.87, P < 0.00001), superior response rate (risk ratio [RR] 1.69, 95% CI 1.47–1.95, P < 0.0001), and disease control rate (RR 1.19, 95% CI 1.08–1.32, P < 0.00001). Subgroup analyses indicated that patient treated with monoclonal antibodies (HR 0.89, 95% CI 0.82–0.96, P = 0.02) as well as application in second-line (HR 0.91, 95% CI 0.85–0.96, P = 0.02) acquired significant OS improvement. Other clinical factors directing significant OS improvement by the combination strategy included nonsquamous cancer (P = 0.002), nonsmokers (P = 0.0005), and female (P = 0.02). Toxicities were greater but generally mild or moderate in the combination group, and were mostly manageable. In summary, the addition of AAs to TCC could improve prognosis of advanced NSCLC. Furthermore, proper selection of patient population and AAs is crucial for clinical trials design and clinical practice in the future. PMID:26252298

Haematological toxicity of Valproic acid compared to Levetiracetam in patients with glioblastoma multiforme undergoing concomitant radio-chemotherapy: a retrospective cohort study.

PubMed

Tinchon, Alexander; Oberndorfer, Stefan; Marosi, Christine; Gleiss, Andreas; Geroldinger, Angelika; Sax, Cornelia; Sherif, Camillo; Moser, Walter; Grisold, Wolfgang

2015-01-01

Patients with glioblastoma multiforme (GBM) and symptomatic seizures are in need of a sufficient antiepileptic treatment. Haematological toxicity is a limiting side effect of both, first line radio-chemotherapy with temozolomide (TMZ) and co-medication with antiepileptic drugs. Valproic acid (VPA) and levetiracetam (LEV) are considered favourable agents in brain tumor patients with seizures, but are commonly reported to induce haematological side effects on their own. We hypothesized, that antiepileptic treatment with these agents has no increased impact on haematological side effects during radio-chemotherapy in the first line setting. We included 104 patients from two neuro-oncologic centres with GBM and standard radio-chemotherapy in a retrospective cohort study. Patients were divided according to their antiepileptic treatment with either VPA, LEV or without antiepileptic drug therapy (control group). Declines in haemoglobin levels and absolute blood cell counts for neutrophil granulocytes, lymphocytes and thrombocytes were analyzed twice during concomitant and once during adjuvant phase. A comparison between the examined groups was performed, using a linear mixed model. Neutrophil granulocytes, lymphocytes and thrombocytes significantly decreased over time in all three groups (all p < 0.012), but there was no significant difference between the compared groups. A significant decline in haemoglobin was observed in the LEV treated group (p = 0.044), but did not differ between the compared groups. As a novel finding, this study demonstrates that co-medication either with VPA or LEV in GBM patients undergoing first line radio-chemotherapy with TMZ has no additional impact on medium-term haematological toxicity.

The Impact of Combined Radiation and Chemotherapy on Outcome in Uterine Clear Cell Carcinoma Compared with Chemotherapy Alone.

PubMed

Mahdi, H; Moulton, L; Nutter, B; Cherian, S; Rose, P

2016-12-01

To investigate the impact of pelvic radiation on survival in patients with uterine clear cell carcinoma (UCC) who received adjuvant chemotherapy. Patients with stage I-IV UCC who had undergone surgery and chemotherapy were identified from the Surveillance, Epidemiology, and End Results (SEER) programm 2000-2009. Patients were divided into those who received only chemotherapy and those who received both chemotherapy and radiation therapy. Kaplan-Meier curves and Cox regression models were used for analysis. Of the 317 patients included, 195 (62%) were in the chemotherapy only group and 122 (38%) were in the chemotherapy and radiation therapy group. Pelvic radiation was associated with significant improvement in overall survival (median 88 versus 25 months, 5 year survival: 58% versus 33%, P<0.001) in the chemotherapy and radiation therapy group compared with the chemotherapy only group for the entire cohort. On subset analysis, chemotherapy and radiation therapy was associated with improved overall survival in late stage disease (III-IV) (5 year 54% versus 22%, P<0.001) compared with the chemotherapy only group, whereas in stage I-II UCC, there was no difference in overall survival between the chemotherapy and radiotherapy group and the chemotherapy only group (5 year 65% versus 67%, P=0.69). In multivariable analysis, pelvic radiation was associated with improved survival in patients with late stage disease (hazard ratio 0.57, 95% confidence interval 0.35-0.94, P=0.03) but not for early stage disease (hazard ratio 0.81, 95% confidence interval 0.33-2.0, P=0.65). Other significant predictors were advanced stage, positive cytology and extensive lymphadenectomy. Radiation was associated with significant improvement in survival in advanced stage UCC, but not in early stage UCC. These data support the beneficial role of radiation therapy in UCC, especially in patients with advanced stage disease. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier

How Chemotherapy Increases the Risk of Systemic Candidiasis in Cancer Patients: Current Paradigm and Future Directions

PubMed Central

Teoh, Flora; Pavelka, Norman

2016-01-01

Candida albicans is a fungal commensal and a major colonizer of the human skin, as well as of the gastrointestinal and genitourinary tracts. It is also one of the leading causes of opportunistic microbial infections in cancer patients, often presenting in a life-threatening, systemic form. Increased susceptibility to such infections in cancer patients is attributed primarily to chemotherapy-induced depression of innate immune cells and weakened epithelial barriers, which are the body’s first-line defenses against fungal infections. Moreover, classical chemotherapeutic agents also have a detrimental effect on components of the adaptive immune system, which further play important roles in the antifungal response. In this review, we discuss the current paradigm regarding the mechanisms behind the increased risk of systemic candidiasis in cancer patients. We also highlight some recent findings, which suggest that chemotherapy may have more extensive effects beyond the human host, in particular towards C. albicans itself and the bacterial microbiota. The extent to which these additional effects contribute towards the development of candidiasis in chemotherapy-treated patients remains to be investigated. PMID:26784236

Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a collagen-targeted parathyroid hormone analog, in a non-depilated mouse model

PubMed Central

Katikaneni, Ranjitha; Ponnapakkam, Tulasi; Matsushita, Osamu; Sakon, Joshua; Gensure, Robert

2014-01-01

Alopecia is a psychologically devastating complication of chemotherapy for which there is currently no effective therapy. PTH-CBD is a collagen-targeted parathyroid hormone analog that has shown promise as a therapy for alopecia disorders. To compare the efficacy of prophylactic versus therapeutic administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle control before or after hair loss developing from three courses of cyclophosphamide chemotherapy (50–150 mg/kg/week). Mice receiving chemotherapy alone developed hair loss and depigmentation over 6–12 months. Mice pretreated with PTH-CBD did not develop these changes and maintained a normal-appearing coat. Mice treated with PTH-CBD after development of hair loss showed a partial recovery. Observations of hair loss were confirmed quantitatively by gray scale analysis. Histological examination showed that in mice receiving chemotherapy alone, there were small, dystrophic hair follicles mostly in the catagen phase. Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH-CBD was effective in both the prevention and the treatment of chemotherapy-induced alopecia in mice, but pretreatment appears to result in a better cosmetic outcome. PTH-CBD shows promise as an agent in the prevention of this complication of chemotherapy and improving the quality of life for cancer patients. PMID:24025564

Assessment of the Radiation-Equivalent of Chemotherapy Contributions in 1-Phase Radio-chemotherapy Treatment of Muscle-Invasive Bladder Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plataniotis, George A., E-mail: george.plataniotis@nhs.net; Dale, Roger G.

2014-03-15

Purpose: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. Methods and Materials: A standard logistic dose–response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. Results: The respective best-fit values of the independent chemotherapy-induced completemore » response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval −0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. Conclusion: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.« less

Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study.

PubMed

Kimura, Hiroaki; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Igarashi, Kentaro; Inatani, Hiroyuki; Shimozaki, Shingo; Kato, Takashi; Aoki, Yu; Higuchi, Takashi; Tsuchiya, Hiroyuki

2015-03-01

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

DOEpatents

Gakh, Andrei A.; Vovk, Mykhaylo V.; Mel'nychenko, Nina V.; Sukach, Volodymyr A.

2012-08-14

The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

Anti-cancer agents based on 6-trifluoromethoxybenzimidazole derivatives and method of making

DOEpatents

Gakh, Andrei A; Vovk, Mykhaylo V; Mel& #x27; nychenko, Nina V; Sukach, Volodymyr A

2012-10-23

The present disclosure relates to novel compounds having the structural Formulas (1a,1b), stereoisomers, tautomers, racemics, prodrugs, metabolites thereof, or pharmaceutically acceptable salt and/or solvate thereof as chemotherapy agents for treating of cancer, particularly androgen-independent prostate cancer. The disclosure also relates to methods for preparing said compounds, and to pharmaceutical compositions comprising said compounds.

Challenges in management of patients with intracranial germ cell tumor and diabetes insipidus treated with cisplatin and/or ifosfamide based chemotherapy.

PubMed

Afzal, Samina; Wherrett, Diane; Bartels, Ute; Tabori, Uri; Huang, Annie; Stephens, Derek; Bouffet, Eric

2010-05-01

Patients with intracranial germ cell tumor (IGCT) often present with pituitary dysfunction, including diabetes insipidus (DI). Recent protocols have used pre-radiation chemotherapy with combinations of etoposide, carboplatin and/or cisplatin, and ifosfamide. Management of DI in these patients requires monitoring of electrolytes and fluids during chemotherapy and hyperhydration. All consecutive patients treated with chemotherapy for an IGCT during the period 1990-2007 at the Hospital for Sick Children, Toronto were reviewed. Out of 32 patients who received chemotherapy, 21 had DI. Only cycles containing cisplatin and/or ifosfamide and hyperhydration were considered. DI and non-DI patients were compared for each cycle of chemotherapy. Patients were studied for number of days in hospital per chemotherapy course, daily fluid input and output, changes in dose, schedule and route of administration of desmopressin (DDAVP) during chemotherapy, daily variations in sodium level, electrolyte monitoring requirements per day, and complications related to fluid and electrolyte disturbances. Fifty-four cycles of chemotherapy in DI patients were compared to 25 cycles in non DI patients. All 21 patients with DI required daily change in dosage and schedule of DDAVP. Marked variations in daily sodium level were observed in the DI group. Seventeen courses required prolonged admission in the DI group (one in non DI patients) and 6 patients experienced serious complications. In conclusion, DI is a risk factor for complications when cisplatin and/or ifosfamide based protocols are used. The role of these agents in the management of ICGT should be carefully evaluated and guidelines for management of DI established.

Pulmonary delivery of nanoparticle chemotherapy for the treatment of lung cancers: challenges and opportunities

PubMed Central

Mangal, Sharad; Gao, Wei; Li, Tonglei; Zhou, Qi (Tony)

2017-01-01

Lung cancer is the second most prevalent and the deadliest among all cancer types. Chemotherapy is recommended for lung cancers to control tumor growth and to prolong patient survival. Systemic chemotherapy typically has very limited efficacy as well as severe systemic adverse effects, which are often attributed to the distribution of anticancer drugs to non-targeted sites. In contrast, inhalation routes permit the delivery of drugs directly to the lungs providing high local concentrations that may enhance the anti-tumor effect while alleviating systemic adverse effects. Preliminary studies in animals and humans have suggested that most inhaled chemotherapies are tolerable with manageable pulmonary adverse effects, including cough and bronchospasm. Promoting the deposition of anticancer drugs in tumorous cells and minimizing access to healthy lung cells can further augment the efficacy and reduce the risk of local toxicities caused by inhaled chemotherapy. Sustained release and tumor localization characteristics make nanoparticle formulations a promising candidate for the inhaled delivery of chemotherapeutic agents against lung cancers. However, the physiology of respiratory tracts and lung clearance mechanisms present key barriers for the effective deposition and retention of inhaled nanoparticle formulations in the lungs. Recent research has focused on the development of novel formulations to maximize lung deposition and to minimize pulmonary clearance of inhaled nanoparticles. This article systematically reviews the challenges and opportunities for the pulmonary delivery of nanoparticle formulations for the treatment of lung cancers. PMID:28504252

Chemotherapy

MedlinePlus

... tests and imaging tests, such as x-rays, MRI , CT , or PET scans will be done to: Monitor how well the chemotherapy is working Watch for damage to the heart, lungs, kidneys, blood, and other parts of the body

Correlation of Early Recurrence With In Vitro Adenosine Triphosphate Based Chemotherapy Response Assay in Pancreas Cancer With Postoperative Gemcitabine Chemotherapy.

PubMed

Park, Joon Seong; Kim, Jae Keun; Yoon, Dong Sup

2016-11-01

Gemcitabine-based regimens represent the standard systemic first line treatment in patients after pancreatic resection. However, the clinical impact of gemcitabine varies significantly in individuals because of chemoresistance. An in vitro adenosine triphosphate based chemotherapy response assay (ATP-CRA) was designed to evaluate the sensitivity of cancer cells to various chemotherapeutic agents. This study investigated the correlation between in vitro gemcitabine sensitivity of tumor cells and early recurrence after curative resection. From January 2007 to December 2010, the ATP-CRA for gemcitabine was tested in 64 patients surgically treated for pancreas cancer at Gangnam Severance Hospital, Seoul, Korea. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with pancreas cancer to predict disease-free survival (DFS) after curative resection in pancreas cancer. The mean cell death rate (CDR) was 20.0 (±14.5) and divided into two groups according to the mean values of the CDR. Lymphovascular invasion was more frequently shown in gemcitabine resistance group without statistical significance. In univariate and multivariate analysis, advanced tumor stage and gemcitabine sensitive group (CDR ≥ 20) were identified as independent prognostic factors for DFS. Gemcitabine sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence following gemcitabine-based adjuvant chemotherapy in patients with pancreas cancer. © 2016 Wiley Periodicals, Inc.

Prophylactic use of lamivudine for hepatitis B exacerbation in post-operative breast cancer patients receiving anthracycline-based adjuvant chemotherapy.

PubMed

Yun, J; Kim, K H; Kang, E S; Gwak, G-Y; Choi, M S; Lee, J E; Nam, S J; Yang, J-H; Park, Y H; Ahn, J S; Im, Y-H

2011-02-15

With the increasing incidence of breast cancer worldwide, in particular in southeast Asia (including Korea), and the common use of anthracyclines in the adjuvant and metastatic settings, the occurrence of Hepatitis B virus (HBV) reactivation may develop in this patient population. The use of prophylactic antiviral agents in cancer patients may result in a reduced HBV exacerbation. The purpose of the current study was to assess the efficacy of prophylactic lamivudine in reducing the incidence and severity of HBV reactivation in post-operative breast cancer patients undergoing adjuvant doxorubicin-containing chemotherapy. The medical records of patients undergoing anthracycline-based adjuvant chemotherapy at Samsung Medical Center between January 2001 and September 2008 were reviewed. From the database, 1912 breast cancer patients who had received anthracycline-based adjuvant chemotherapy were identified. Of 131 patients who were HBV surface antigen positive, 55 and 76 did and did not receive prophylactic lamivudine, respectively. In all, 30 patients (23%) developed hepatitis during doxorubicin-containing adjuvant chemotherapy. Of the 30 patients, 5 (9%) were in the prophylactic lamivudine group and 25 (33%) in the control group (P=0.001). In the prophylactic lamivudine group, there was significantly less HBV reactivation (1 patient (2%) vs 20 patients (16%); P=0.002), less disruption of chemotherapy (7 vs 14%; P=0.04), and less severe hepatitis (0 vs 17%; P=0.002). Prophylactic lamivudine significantly reduced the incidence and severity of HBV reactivation in breast cancer patients undergoing anthracycline-based adjuvant chemotherapy.

[The Effectiveness of Cooling Packaging Care in Relieving Chemotherapy-Induced Skin Toxicity Reactions in Cancer Patients Receiving Chemotherapy: A Systematic Review].

PubMed

Hsu, Ya-Hui; Hung, Hsing-Wei; Chen, Shu-Ching

2017-08-01

Anti-cancer chemotherapy may cause skin-toxicity reactions. Different types of cooling packages affect chemotherapy-induced skin toxicity reactions differently. To evaluate the effects of cooling packing care on chemotherapy-induced skin toxicity reactions in cancer patients receiving chemotherapy. A systematic review approach was used. Searches were conducted in databases including Cochrane Library, Embase, MEDLINE, PubMed and Airiti Library using the keywords "chemotherapy cutaneous toxicity", "chemotherapy skin reaction", "chemotherapy skin toxicity", "frozen glove", "frozen sock", "cooling packaging care", "ice gloves", "ice socks", "usual care", "severity", "comfort", "satisfaction", "severity", and "comfort". The search focused on articles published before December 2016. Based on the inclusion and exclusion criteria, 5 articles involving relevant randomized controlled trials were extracted for review. Elasto-Gel ice gloves or ice socks that were chilled to -25°C- -30°C and used for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy were shown to improve the frequency and severity of chemotherapy-induced skin toxicity reactions. Several studies were limited by small sample sizes and different types of cooling packing programs, temperature, timing, and frequency. Thus, further research is recommended to verify the effects of cooling packing care. Cancer patients who were treated with docetaxel or PLD and who used ice gloves or ice socks that were chilled to -25°C- -30°C for 15 mins during initial chemotherapy, for one hour during chemotherapy infusion, and for 15 mins after chemotherapy improved significantly in terms of the frequency and severity of their chemotherapy-induced skin toxicity reactions. Local cooling packing care is a non-pharmacotherapy approach that is low cost and free of side effects. This review is intended to provide a reference for clinical care.

Stem cells as anticancer drug carrier to reduce the chemotherapy side effect

NASA Astrophysics Data System (ADS)

Salehi, Hamideh; Al-Arag, Siham; Middendorp, Elodie; Gergley, Csilla; Cuisinier, Frederic

2017-02-01

Chemotherapy used for cancer treatment, due to the lack of specificity of drugs, is associated to various damaging side effects that have severe impact on patients' quality of life. Over the past 30 years, increasing efforts have been placed on optimizing chemotherapy dosing with the main goal of increasing antitumor efficacy while reducing drug-associated toxicity. A novel research shows that stem cells may act as a reservoir for the anticancer agent, which will subsequently release some of the drug's metabolites, or even the drug in its original form, in vicinity of the cancer cells. These cells may play a dual role in controlling drug toxicity depending on their capacity to uptake and release the chemotherapeutic drug. In our study, we show that Dental Pulp Stem Cells DPSCs are able to rapidly uptake Paclitaxel PTX, and to release it in the culture medium in a time-dependent manner. This resulting conditioned culture medium is to be transferred to breast cancer cells, the MCF-7. By applying Confocal Raman Microscopy, the anticancer drug uptake by the MCF-7 was measured. Surprisingly, the cancer cells -without any direct contact with PTX- showed a drug uptake. This proves that the stem cells carried and delivered the anticancer drug without its modification. It could be a revolution in chemotherapy to avoid the drug's side effects and increase its efficacy.

Assessment of apoptosis in oesophageal carcinoma preoperatively treated by chemotherapy and radiotherapy.

PubMed

Moreira, L F; Naomoto, Y; Hamada, M; Kamikawa, Y; Orita, K

1995-01-01

Apoptosis, programmed cell death, was immunohistochemically determined in 55 samples of oesophageal squamous cell carcinoma using the BM1 Mab. Sections from patients not treated (group 1, n = 12) or preoperatively treated by chemotherapy (group 2, n = 11), radiation (group 3, n = 13) or both (group 4, n = 8), and 11 additional cases of high-grade dysplasia or early cancer were examined. Most of the apoptotic cells were BM1-positive and checked by TUNEL proved to be nick end positive. They accounted for 7 (11%), 19 (29%), 21 (32%) and 26 (38%) cells per field in those 4 groups respectively. Chemotherapy and/or radiation significantly increased the number of apoptotic cells as compared to controls (p = 0.029 and p = 0.029, respectively). To assess the implications of the oncogene expression in the apoptotic pathway, additional section stained with bcl2 and p53 were negative for bcl2 and were positive for p53 in 16 samples (37%). Overall, positive cases for p53 mutation showed a significantly decreased incidence of apoptotic cells (p = 0.03). These results suggest that in situ assessment of apoptotic response better correlates to the apoptosis induced by radiation than that by chemotherapy, that abnormalities of the p53 protein decrease the apoptotic response in oesophageal carcinoma, and that immunohistochemical analysis of p53 protein helps to determine the sensitivity to these anticancer agents.

Metronomic low-dose chemotherapy boosts CD95-dependent antiangiogenic effect of the thrombospondin peptide ABT-510: a complementation antiangiogenic strategy.

PubMed

Yap, Ronald; Veliceasa, Dorina; Emmenegger, Urban; Kerbel, Robert S; McKay, Laura M; Henkin, Jack; Volpert, Olga V

2005-09-15

Blocking angiogenesis is a promising approach in cancer therapy. Natural inhibitors of angiogenesis and derivatives induce receptor-mediated signals, which often result in the endothelial cell death. Low-dose chemotherapy, given at short regular intervals with no prolonged breaks (metronomic chemotherapy), also targets angiogenesis by obliterating proliferating endothelial cells and circulating endothelial cell precursors. ABT-510, a peptide derivative of thrombospondin, kills endothelial cell by increasing CD95L, a ligand for the CD95 death receptor. However, CD95 expression itself is unaffected by ABT-510 and limits its efficacy. We found that multiple chemotherapy agents, cyclophosphamide (cytoxan), cisplatin, and docetaxel, induced endothelial CD95 in vitro and in vivo at low doses that failed to kill endothelial cells (cytoxan > cisplatin > docetaxel). Thus, we concluded that some of these agents might complement each other and together block angiogenesis with maximal efficacy. As a proof of principle, we designed an antiangiogenic cocktail combining ABT-510 with cytoxan or cisplatin. Cyclophosphamide and cisplatin synergistically increased in vivo endothelial cell apoptosis and angiosuppression by ABT-510. This synergy required CD95, as it was reversible with the CD95 decoy receptor. In a mouse model, ABT-510 and cytoxan, applied together at low doses, acted in synergy to delay tumor take, to stabilize the growth of established tumors, and to cause a long-term progression delay of PC-3 prostate carcinoma. These antitumor effects were accompanied by major decreases in microvascular density and concomitant increases of the vascular CD95, CD95L, and apoptosis. Thus, our study shows a "complementation" design of an optimal cancer treatment with the antiangiogenic peptide and a metronomic chemotherapy.

α-Lipoic acid stabilized DTX/IR780 micelles for photoacoustic/fluorescence imaging guided photothermal therapy/chemotherapy of breast cancer.

PubMed

Li, WenTing; Peng, JinRong; Yang, Qian; Chen, LiJuan; Zhang, Lan; Chen, XiaoXin; Qian, ZhiYong

2018-05-01

Micellar nanoparticles have unique advantages as carriers for therapeutic or imaging agents, owing to their smaller size and better penetration of tumors. However, some agents, due to their physical or chemical properties, are difficult to load into micelles. IR780 is one of these agents, and is also a promising near-infrared dye for fluorescence imaging (FI)/photoacoustic imaging (PAI) and cancer photothermal therapy (PTT). Its hydrophobic and high crystallization structure results in limited bioavailability in vivo. It is difficult to load into micelles constructed from an amphiphilic block polymer with relatively low molecular weight. In this study, we use computer simulation and introduce another small biomolecule, α-lipoic acid, into the micelles constructed from a mPEG-PCL copolymer, to lower the energy of molecular interaction between MPEG-PCL and IR780, and expect to enhance the loading capacity of the micelles to IR780. The introduction of α-lipoic acid decreases the energy of molecular interaction between MEPG-PCL and IR780 from -46.18 kJ mol-1 to -196.52 kJ mol-1 and increases the loading capacity and stability of the mPEG-PCL micelles to IR780, which also maintains the loading capacity to DTX. We further construct DTX/IR780 co-loaded mPEG-PCL micelles for FI/PAI dual modal imaging guided PTT/chemotherapy of cancer. By FI and PAI evaluation in vitro and in vivo, we demonstrate that the DTX/IR780 co-loaded micelles can be used as FI and PAI probes. By further evaluating the therapeutic outcome of PTT/chemotherapy co-therapy of breast cancer, we demonstrate that the DTX/IR780 co-loaded mPEG-PCL micelles can serve as promising candidates for FI and PAI guided PTT/chemotherapy of breast cancer.

Nursing Care of Patients Undergoing Chemotherapy Desensitization: Part I.

PubMed

Jakel, Patricia; Carsten, Cynthia; Braskett, Melinda; Carino, Arvie

2016-02-01

Hypersensitivity reactions to chemotherapeutic agents can cause the discontinuation of first-line therapies. Chemotherapy desensitization is a safe, but labor-intensive, process to administer these important medications. A desensitization protocol can enable a patient to receive the entire target dose of a medication, even if the patient has a history of severe infusion reactions. In this article, the authors explain the pathophysiology of hypersensitivity reactions and describe the recent development of desensitization protocols in oncology. In part II of this article, which will appear in the April 2016 issue of the Clinical Journal of Oncology Nursing, the authors will give a detailed account of how a desensitization protocol is performed at an academic medical center.
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Managing Chemotherapy Side Effects: Constipation

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods ... SERVICES National Institutes of Health Managing Chemotherapy Side Effects: Constipation These foods may help if you are ...

Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

PubMed Central

Porter, Holly A.; Carey, Gregory B.; Keegan, Achsah D.

2012-01-01

The adaptors IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. PMID:22652453

Alternative chemotherapeutic agents: nitrosoureas, cisplatin, irinotecan.

PubMed

Carrillo, Jose A; Munoz, Claudia A

2012-04-01

Irinotecan, cisplatin, and nitrosoureas have a long history of use in brain tumors, with demonstrated efficacy in the adjuvant treatment of malignant gliomas. In the era of temozolomide with concurrent radiotherapy given as the standard of care, their use has shifted to treatment at progression or recurrence. Now with the widespread use of bevacizumab in the recurrent setting, irinotecan and other chemotherapies are seeing increased use in combination with bevacizumab and alone in the recurrent setting. The activity of these chemotherapeutic agents in brain tumors will likely ensure a place in the armamentarium of neuro-oncologists for many years. Published by Elsevier Inc.

Managing Chemotherapy Side Effects: Pain

MedlinePlus

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

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

Subcutaneous panniculitic T-cell lymphoma in children: response to combination therapy with cyclosporine and chemotherapy.

PubMed

Shani-Adir, Ayelet; Lucky, Anne W; Prendiville, Julie; Murphy, Sharon; Passo, Murray; Huang, Frederick S; Paller, Amy S

2004-02-01

We describe 2 adolescent boys with facial swelling and/or subcutaneous nodules and fever. Extensive evaluation, including several biopsy specimens, led to a diagnosis of subcutaneous panniculitic T-cell lymphoma, an entity rarely seen in children. Both patients were treated with oral cyclosporine in an effort to suppress the cytokine release from T-cells that has been thought to induce the hemophagocytic syndrome. The patients responded dramatically to cyclosporine treatment with defervescence of the fever and reduction in number and size of the subcutaneous nodules. Subsequent therapy with multidrug chemotherapy achieved complete remission in the first patient. This report suggests the value of cyclosporine as a first-line agent coupled with chemotherapy in the treatment of patients with subcutaneous panniculitic T-cell lymphoma. A clinicopathologic review of 8 described pediatric cases of subcutaneous panniculitic T-cell lymphoma is also presented.

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

PubMed Central

Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

2010-01-01

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

Low-level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA).

PubMed

Wikramanayake, Tongyu Cao; Villasante, Alexandra C; Mauro, Lucia M; Nouri, Keyvan; Schachner, Lawrence A; Perez, Carmen I; Jimenez, Joaquin J

2013-05-01

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrated that LaserComb treatment induced hair regrowth in a mouse model for alopecia areata. In the current study, we tested whether LLL treatment could promote hair regrowth in a rat model for CIA. Chemotherapy agents cyclophosphamide, etoposide, or a combination of cyclophosphamide and doxorubicin were administered in young rats to induce alopecia, with or without LLL treatment. As expected, 7-10 days later, all the rats developed full body alopecia. However, rats receiving laser treatment regrew hair 5 days earlier than rats receiving chemotherapy alone or sham laser treatment (with the laser turned off). The accelerated hair regrowth in laser-treated rats was confirmed by histology. In addition, LLL treatment did not provide local protection to subcutaneously injected Shay chloroleukemic cells. Taken together, our results demonstrated that LLL treatment significantly accelerated hair regrowth after CIA without compromising the efficacy of chemotherapy in our rat model. Our results suggest that LLL should be explored for the treatment of CIA in clinical trials because LLL devices for home use (such as the HairMax LaserComb®) provide a user-friendly and noninvasive approach that could be translated to increased patient compliance and improved efficacy.

Implementing oral chemotherapy services in community pharmacies: a qualitative study of chemotherapy nurses' and pharmacists' views.

PubMed

Butt, Farida; Ream, Emma

2016-05-01

Changes in health-care provision have led to cancer patients being offered oral chemotherapy in the community. Three levels of oral chemotherapy services have been proposed (levels 1, 2 and 3) with community pharmacies playing differing roles within them. This study aims to explore health-care professionals' views on oral chemotherapy services being delivered by community pharmacies and to gain insights into the barriers, facilitators and training/knowledge needs of community pharmacists with respect to providing them. Qualitative semi-structured interviews were conducted with a purposive sample of three chemotherapy nurses, five oncology pharmacists and five community pharmacists. Data were analysed thematically using Framework Analysis. Findings for level 1 and 2 services included uncertainty on community pharmacists' professional responsibilities, the expertise of GPs in prescribing oral chemotherapy and the training and competency of community pharmacists. The lack of patient information, care and support provision was emphasised for all the models. Although level 1 was achievable in current practice, level 2 was considered the safest option, while level 3 was ideal but risky option. For all levels, training and education for community pharmacists and inter-professional issues were facilitators to oral chemotherapy services. The service environment, dispensing process-related constraints (access to blood test results and protocols) were significant barriers for levels 2 and 3. Advanced communication skills, patient education and counselling were identified as key areas for education and training for community pharmacists. The study suggests there are significant concerns and challenges associated with community pharmacies implementing any of the proposed levels of oral chemotherapy services. Educational and training opportunities for community pharmacists and the careful development of safe infrastructures will be essential in the future planning and

Managing Chemotherapy Side Effects: Anemia

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Anemia “I told my doctor that I was ... exercise a little every day. Managing Chemotherapy Side Effects: Anemia Eat and drink well. ● ● Talk with your ...

Neurotoxic Effects of Anthracycline- vs Nonanthracycline-Based Chemotherapy on Cognition in Breast Cancer Survivors.

PubMed

Kesler, Shelli R; Blayney, Douglas W

2016-02-01

Chemotherapy exposure is a known risk factor for cancer-related cognitive impairments. Anthracycline-based regimens are commonly used chemotherapies that have been shown to be associated with cognitive impairment and brain changes in clinical studies. To directly compare the effects of anthracycline and nonanthracycline regimens on cognitive status and functional brain connectivity. In this observational study, we retrospectively examined cognitive and resting state functional magnetic resonance imaging data acquired from 62 primary breast cancer survivors (mean [SD] age, 54.7 [8.5] years) who were more than 2 years off-therapy, on average. Twenty of these women received anthracycline-based chemotherapy as part of their primary treatment, 19 received nonanthracycline regimens, and 23 did not receive any chemotherapy. Participants were enrolled at a single academic institution (Stanford University) from 2008 to 2014, and the study analyses were performed at this time. Cognitive status was measured using standardized neuropsychological tests, and functional brain connectivity was evaluated using resting state functional magnetic resonance imaging with a focus on the brain's default mode network. The anthracycline group demonstrated significantly lower verbal memory performance including immediate recall (F = 3.73; P = .03) and delayed recall (F = 11.11; P < .001) as well as lower left precuneus connectivity (F = 7.48; P = .001) compared with the other 2 groups. Patient-reported outcomes related to cognitive dysfunction (F = 7.27; P = .002) and psychological distress (F = 5.64; P = .006) were similarly elevated in both chemotherapy groups compared with the non-chemotherapy-treated controls. These results suggest that anthracyclines may have greater negative effects than nonanthracycline regimens on particular cognitive domains and brain network connections. Both anthracycline and nonanthracycline regimens may have nonspecific effects on other cognitive

Medical visits for chemotherapy and chemotherapy-induced neutropenia: a survey of the impact on patient time and activities

PubMed Central

Fortner, Barry V; Tauer, Kurt; Zhu, Ling; Okon, Theodore A; Moore, Kelley; Templeton, Davis; Schwartzberg, Lee

2004-01-01

Background Patients with cancer must make frequent visits to the clinic not only for chemotherapy but also for the management of treatment-related adverse effects. Neutropenia, the most common dose-limiting toxicity of myelosuppressive chemotherapy, has substantial clinical and economic consequences. Colony-stimulating factors such as filgrastim and pegfilgrastim can reduce the incidence of neutropenia, but the clinic visits for these treatments can disrupt patients' routines and activities. Methods We surveyed patients to assess how clinic visits for treatment with chemotherapy and the management of neutropenia affect their time and activities. Results The mean amounts of time affected by these visits ranged from approximately 109 hours (hospitalization for neutropenia) and 8 hours (physician and chemotherapy) to less than 3 hours (laboratory and treatment with filgrastim or pegfilgrastim). The visits for filgrastim or pegfilgrastim were comparable in length, but treatment with filgrastim requires several visits per chemotherapy cycle and treatment with pegfilgrastim requires only 1 visit. Conclusions This study provides useful information for future modelling of additional factors such as disease status and chemotherapy schedule and provides information that should be considered in managing chemotherapy-induced neutropenia. PMID:15153249

Hypothermia for preventing chemotherapy-induced neuropathy - a pilot study on safety and tolerability in healthy controls.

PubMed

Bandla, Aishwarya; Sundar, Raghav; Liao, Lun-De; Sze Hui Tan, Stacey; Lee, Soo-Chin; Thakor, Nitish V; Wilder-Smith, Einar P V

2016-01-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of several chemotherapeutic agents, often leading to treatment discontinuation. Up to 20% of patients treated with weekly paclitaxel experience severe CIPN and no effective treatment has been established so far. The mechanisms of CIPN damage are unclear, but are directly dose-related. We had earlier demonstrated, in rats, the influence of hypothermia in reducing nerve blood flow. Here, we hypothesize that continuous flow limb hypothermia during chemotherapy reduces the incidence and severity of CIPN, by limiting deliverance of the neurotoxic drug to the peripheral nerves. In this study, prior to assessing the effect of hypothermia in preventing CIPN in cancer subjects undergoing paclitaxel chemotherapy, we assess the safety and tolerable temperatures for limb hypothermia in healthy human subjects. In 15 healthy human subjects, hypothermia was administered as continuous flow cooling, unilaterally, via a thermoregulator setup covering the digits up to the elbow/knee, along with continuous skin temperature monitoring. Thermoregulator coolant temperatures between 25 °C and 20 °C were tested for tolerability, based on a carefully designed temperature regulation protocol, and maintained for three hours mimicking the duration of chemotherapy. Tolerability was evaluated using various safety and tolerability scores to monitor the subjects. At the end of the cooling session the healthy subjects presented without significant adverse effects, the main being brief mild skin erythema and transient numbness. Coolant temperatures as low as 22 °C were well tolerated continuously over three hours. Our results confirm the safety and tolerability of continuous flow limb hypothermia in healthy subjects. Further studies will use 22 °C thermoregulator temperature to investigate hypothermia in preventing CIPN in breast cancer patients receiving adjuvant weekly paclitaxel. This pilot study

Modifying mesoporous silica nanoparticles to avoid the metabolic deactivation of 6-mercaptopurine and methotrexate in combinatorial chemotherapy.

PubMed

Wang, Wenjing; Fang, Chenjie; Wang, Xiaozhu; Chen, Yuxi; Wang, Yaonan; Feng, Wei; Yan, Chunhua; Zhao, Ming; Peng, Shiqi

2013-07-21

Mesoporous silica nanoparticles with amino and thiol groups (MSNSN) were prepared and covalently modified with methotrexate and 6-mercaptopurine to form 6-MP-MSNSN-MTX. In the presence of DTT, 6-MP-MSNSN-MTX gradually releases 6-MP. In rat plasma, 6-MP-MSNSN-MTX effectively inhibits the metabolic deactivation of 6-MP and MTX. 6-MP-MSNSN-MTX could be an agent for long-acting chemotherapy.

Survival of multiple myeloma patients aged 65-70 years in the era of novel agents and autologous stem cell transplantation. A multicenter retrospective collaborative study of the Japanese Society of Myeloma and the European Myeloma Network.

PubMed

Ozaki, Shuji; Harada, Takeshi; Saitoh, Takayuki; Shimazaki, Chihiro; Itagaki, Mitsuhiro; Asaoku, Hideki; Kuroda, Yoshiaki; Chou, Takaaki; Yoshiki, Yumiko; Suzuki, Kenshi; Murakami, Hirokazu; Hayashi, Kunihiko; Mina, Roberto; Palumbo, Antonio; Shimizu, Kazuyuki

2014-01-01

Novel agents such as thalidomide, lenalidomide and bortezomib have dramatically changed the treatment paradigm of multiple myeloma (MM). However, it is not clear whether these agents improve the prognosis of elderly patients who have undergone autologous stem cell transplantation (auto-SCT). We retrospectively analyzed the outcome of 318 newly diagnosed patients aged 65–70 years who were treated between January 1, 2004, and December 31, 2009. As initial therapy, 192 patients were treated with conventional chemotherapy,88 with novel agent-containing regimens, 21 with conventional chemotherapy plus auto-SCT and the remaining 17 with novel agents plus auto-SCT. The median progression-free survival was 19.1, 24.5, 26.8 and 35.2 months, respectively, and the 5-year overall survival (OS) was 40, 62, 63 and 87%, respectively. Initial therapy with novel agents (p < 0.001) or auto-SCT (p < 0.02) significantly improved OS compared with the group without these treatment modalities. Salvage therapy with novel agents also significantly improved survival after relapse compared with conventional chemotherapy alone (p < 0.04). In a multivariate analysis, the use of novel agents was an independent prognostic factor significantly associated with extended OS(p < 0.003). These results indicate that novel agents and auto-SCT had a major impact on OS in eligible patients in this subgroup of MM. © 2014 S. Karger AG, Basel

The development of targeted new agents to improve the outcome for children with leukemia.

PubMed

Bautista, Francisco; Van der Lugt, Jasper; Kearns, Pamela R; Mussai, Francis J; Zwaan, C Michel; Moreno, Lucas

2016-11-01

Survival rates in pediatric leukemia have greatly improved in the last decades but still a substantial number of patients will relapse and die. New agents are necessary to overcome the limitations of conventional chemotherapy and hematopoietic stem cell transplantation and to reduce their undesirable long-term toxicities. The identification of driving molecular alterations of leukemogenesis in subsets of patients will allow the incorporation of new-targeted therapies. Areas covered: In this article the authors present a detailed review of the most recent advances in targeted therapies for pediatric leukemias. A comprehensive description of the biological background, adult data and early clinical trials in pediatrics is provided. Expert opinion: Clinical trials are the way to evaluate new agents in pediatric cancer. The development of new drugs in pediatric leukemia must be preceded by a solid biological rationale. Agents in development exploit all possible vulnerabilities of leukemic cells. Drugs targeting cell surface antigens, intracellular signaling pathways and cell cycle inhibitors or epigenetic regulators are most prominent. Major advances have occurred thanks to new developments in engineering leading to optimized molecules such as anti-CD19 bi-specific T-cell engagers (e.g. blinatumomab) and antibody-drug conjugates. The integration of new-targeted therapies in pediatric chemotherapy-based regimens will lead to improved outcomes.

Prediction of clinical response to drugs in ovarian cancer using the chemotherapy resistance test (CTR-test).

PubMed

Kischkel, Frank Christian; Meyer, Carina; Eich, Julia; Nassir, Mani; Mentze, Monika; Braicu, Ioana; Kopp-Schneider, Annette; Sehouli, Jalid

2017-10-27

In order to validate if the test result of the Chemotherapy Resistance Test (CTR-Test) is able to predict the resistances or sensitivities of tumors in ovarian cancer patients to drugs, the CTR-Test result and the corresponding clinical response of individual patients were correlated retrospectively. Results were compared to previous recorded correlations. The CTR-Test was performed on tumor samples from 52 ovarian cancer patients for specific chemotherapeutic drugs. Patients were treated with monotherapies or drug combinations. Resistances were classified as extreme (ER), medium (MR) or slight (SR) resistance in the CTR-Test. Combination treatment resistances were transformed by a scoring system into these classifications. Accurate sensitivity prediction was accomplished in 79% of the cases and accurate prediction of resistance in 100% of the cases in the total data set. The data set of single agent treatment and drug combination treatment were analyzed individually. Single agent treatment lead to an accurate sensitivity in 44% of the cases and the drug combination to 95% accuracy. The detection of resistances was in both cases to 100% correct. ROC curve analysis indicates that the CTR-Test result correlates with the clinical response, at least for the combination chemotherapy. Those values are similar or better than the values from a publication from 1990. Chemotherapy resistance testing in vitro via the CTR-Test is able to accurately detect resistances in ovarian cancer patients. These numbers confirm and even exceed results published in 1990. Better sensitivity detection might be caused by a higher percentage of drug combinations tested in 2012 compared to 1990. Our study confirms the functionality of the CTR-Test to plan an efficient chemotherapeutic treatment for ovarian cancer patients.

Proteomics as a Guide for Personalized Adjuvant Chemotherapy in Patients with Early Breast Cancer.

PubMed

Lumachi, Franco; Chiara, Giordano B; Foltran, Luisa; Basso, Stefano M M

2015-01-01

Proteomics allows for better understanding of the function and regulation of cancer cells mediated by intra- and extracellular signaling networks. Integrating such information with clinicopathological characteristics of the tumor may lead to either detection of disease biomarkers useful to differentiate high-from low-risk patients, or to identification of new drug targets. Adjuvant chemotherapy is currently a personalized treatment strategy, especially for breast cancer (BC) patients, and the risk assessment of each patient influences its use because the benefit strictly correlates with the level of risk. Luminal A BCs are endocrine therapy (ET)-sensitive but exhibit low sensitivity to chemotherapy, while luminal B cancers, according to the Ki-67 proliferation rate may require for chemotherapy in addition to ET, and HER2-positive tumors derive benefit from adjuvant chemotherapy containing an anthracycline, a taxane and trastuzumab for one year. Triple-negative BCs have a high degree of genomic instability exhibiting a more aggressive clinical course with respect to other types of BC, and the anthracycline-taxane regimen constitutes the standard approach. Studies considering the use of targeted approaches (drugs), including poly (ADP-ribose) polymerase (PARP-1), vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) inhibitors, or EFGR and HER2 blockers, are still under evaluation. In the genomic era, promising new targeted-therapies are worthy of further investigation, and mTOR inhibitors have been used for patients with high-risk ER-positive and HER2-negative tumors. In the near future, genetic and molecular profiling of BC will help to better-categorize patients, determine the choice of chemotherapy in low-risk, or intensify the treatment in high-risk cancer patients, eventually revealing new targeted agents. Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

PubMed Central

Aabo, K.; Adams, M.; Adnitt, P.; Alberts, D. S.; Athanazziou, A.; Barley, V.; Bell, D. R.; Bianchi, U.; Bolis, G.; Brady, M. F.; Brodovsky, H. S.; Bruckner, H.; Buyse, M.; Canetta, R.; Chylak, V.; Cohen, C. J.; Colombo, N.; Conte, P. F.; Crowther, D.; Edmonson, J. H.; Gennatas, C.; Gilbey, E.; Gore, M.; Guthrie, D.; Yeap, B. Y.

1998-01-01

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients. Images Figure 1 Figure 2 Figure 3 PMID:9836481

Can Some Marine-Derived Fungal Metabolites Become Actual Anticancer Agents?

PubMed

Gomes, Nelson G M; Lefranc, Florence; Kijjoa, Anake; Kiss, Robert

2015-06-19

Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term "cytotoxicity" to be synonymous with "anticancer agent", which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms.

Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma

PubMed Central

Galaal, Khadra; Godfrey, Keith; Naik, Raj; Kucukmetin, Ali; Bryant, Andrew

2014-01-01

Background Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of patients with advanced uterine carcinosarcoma is poor with pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. Objectives To evaluate the effectiveness and safety of radiotherapy and/or systemic chemotherapy in the management of stage III-IV persistent or recurrent uterine carcinosarcoma. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, CENTRAL, The Cochrane Library 2010, Issue 2, MEDLINE and EMBASE to May 2010. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. Data collection and analysis We independently abstracted data and assessed risk of bias. We pooled hazard ratios (HRs) for overall and progression-free survival and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy in meta-analyses. Main results Three trials (579 women, of whom all were assessed at the end of the trials) met the inclusion criteria. Two trials (373 women with stage III-IV persistent or recurrent disease) found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide. There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, which affected significantly more women in the combination therapy group than in the ifosamide group. One trial found no statistically significant difference in the risk of death and disease progression in women who received whole abdominal irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95

Tumor-treating fields plus chemotherapy versus chemotherapy alone for glioblastoma at first recurrence: a post hoc analysis of the EF-14 trial

PubMed Central

Kesari, Santosh; Ram, Zvi

2017-01-01

Background: This post hoc analysis of the EF-14 trial (NCT00916409) of tumor-treating fields (TTFields) plus temozolomide versus temozolomide alone in newly diagnosed glioblastoma compared the efficacy of TTFields plus chemotherapy (physician’s choice) versus chemotherapy alone after first recurrence. Methods: Patients on TTFields plus temozolomide continued TTFields plus second-line chemotherapy after first recurrence. Some patients on temozolomide alone crossed over after approval of TTFields for recurrent GBM. The primary efficacy outcome was overall survival (OS). Results: After disease progression, 131 patients received TTFields plus chemotherapy and 73 chemotherapy alone. Thirteen patients in the original temozolomide-alone group crossed over to receive TTFields plus chemotherapy after disease progression, resulting in 144 patients receiving TTFields plus chemotherapy and 60 chemotherapy alone. Median follow-up was 12.6 months. Bevacizumab, alone or with cytotoxic chemotherapy, was the most frequent treatment. Median OS in the TTFields plus chemotherapy group was significantly longer versus chemotherapy alone (11.8 vs 9.2 months; HR: 0.70; 95% CI, 0.48–1.00; p=0.049). TTFields showed a low toxicity safety profile, as previously reported, with no grade 3/4 device-related adverse events. Conclusion: TTFields plus chemotherapy after first disease recurrence on TTFields plus temozolomide or temozolomide alone prolonged OS in patients in the EF-14 trial. PMID:28399638

Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

PubMed

Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

2017-12-29

To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Olanzapine is effective for refractory chemotherapy-induced nausea and vomiting irrespective of chemotherapy emetogenicity.

PubMed

Vig, Sierra; Seibert, Laurel; Green, Myke R

2014-01-01

The role of olanzapine added to a dopamine antagonist and benzodiazepine for the treatment of refractory chemotherapy-induced nausea and vomiting (CINV) is incompletely characterized in all levels of chemotherapy emetogenicity. This retrospective study evaluated the efficacy of the addition of olanzapine in adults experiencing refractory CINV stratified by chemotherapy emetogenicity. Thirty-three adults who experienced CINV refractory to guideline-recommended prophylaxis and breakthrough antiemetics (dopamine antagonists and benzodiazepines) and received at least one dose of olanzapine 5-10 mg per os were evaluated. Failure was defined as >5 emesis events in 24 h or more than 10 cumulative doses of rescue antiemetics following first olanzapine dose per treatment cycle. Post hoc analyses investigated variables impacting olanzapine efficacy. The addition of olanzapine demonstrated an overall success rate of 70 %. This success rate did not differ between chemotherapy regimens of high versus low-to-moderate emetogenicity (p = 0.79), prophylaxis with serotonin antagonist plus corticosteroid and aprepitant versus serotonin antagonist alone (p = 0.77), or age over 50 versus ≤50 years (p > 0.99). A trend toward greater benefit was seen in women (p = 0.08). The addition of olanzapine to a dopamine antagonist and benzodiazepine demonstrated high efficacy rates for refractory CINV irrespective of chemotherapy emetogenicity. The high success rates among all groups suggests that incomplete resolution of CINV with prophylactic serotonin antagonists and breakthrough dopamine antagonists plus benzodiazepine may benefit from the addition of olanzapine regardless of gender, degree of chemotherapy emetogenicity, number of prophylactic antiemetics, or age. The trend toward greater control of emesis in women merits further investigation.

Clonal Evolution of Chemotherapy-resistant Urothelial Carcinoma

PubMed Central

Faltas, Bishoy M.; Prandi, Davide; Tagawa, Scott T.; Molina, Ana M.; Nanus, David M.; Sternberg, Cora; Rosenberg, Jonathan; Mosquera, Juan Miguel; Robinson, Brian; Elemento, Olivier; Sboner, Andrea; Beltran, Himisha; Demichelis, Francesca; Rubin, Mark A.

2017-01-01

Chemotherapy-resistant urothelial carcinoma (UC) has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs UC’s evolution and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 UCs including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated UC is characterized by intra-patient mutational heterogeneity and the majority of mutations are not shared, (ii) both branching evolution and metastatic spread are very early events in the natural history of UC; (iii) chemotherapy-treated UC is enriched with clonal mutations involving L1-cell adhesion molecule (L1CAM) and integrin signaling pathways; (iv) APOBEC induced-mutagenesis is clonally-enriched in chemotherapy-treated UC and continues to shape UC’s evolution throughout its lifetime. PMID:27749842

Bevacizumab-Based Chemotherapy Combined with Regional Deep Capacitive Hyperthermia in Metastatic Cancer Patients: A Pilot Study.

PubMed

Ranieri, Girolamo; Ferrari, Cristina; Di Palo, Alessandra; Marech, Ilaria; Porcelli, Mariangela; Falagario, Gianmarco; Ritrovato, Fabiana; Ramunni, Luigi; Fanelli, Margherita; Rubini, Giuseppe; Gadaleta, Cosmo Damiano

2017-07-06

As an angiogenesis inhibitor, bevacizumab has been investigated in combination with different chemotherapeutic agents, achieving an established role for metastatic cancer treatment. However, potential synergic anti-angiogenic effects of hyperthermia have not tested to date in literature. The aim of our study was to analyze efficacy, safety, and survival of anti-angiogenic-based chemotherapy associated to regional deep capacitive hyperthermia (HT) in metastatic cancer patients. Twenty-three patients with metastatic colorectal ( n = 16), ovarian ( n = 5), and breast ( n = 2) cancer were treated with HT in addition to a standard bevacizumab-based chemotherapy regimen. Treatment response assessment was performed, according to the modified Response Evaluation Criteria for Solid Tumors (mRECIST), at 80 days (timepoint-1) and at 160 days (timepoint-2) after therapy. Disease Response Rate (DRR), considered as the proportion of patients who had the best response rating (complete response (CR), partial response (PR), or stable disease (SD)), was assessed at timepoint-1 and timepoint-2. Chi-squared for linear trend test was performed to evaluated the association between response groups (R/NR) and the number of previous treatment (none, 1, 2, 3), number of chemotherapy cycles (<6, 6, 12, >12), number of hyperthermia sessions (<12, 12, 24, >24), and lines of chemotherapy (I, II). Survival curves were estimated by Kaplan-Meier method. DRR was 85.7% and 72.2% at timepoint-1 and timepoint-2, respectively. HT was well tolerated without additional adverse effects on chemotherapy-related toxicity. Chi-squared for linear trend test demonstrated that the percentage of responders grew in relation to the number of chemotherapy cycles ( p = 0.015) and to number of HT sessions ( p < 0.001) performed. Both overall survival (OS) and time to progression (TTP) were influenced by the number of chemotherapy cycles ( p < 0.001) and HT sessions ( p < 0.001) performed. Our preliminary data, that

Phase II study of metronomic chemotherapy for recurrent malignant gliomas in adults

PubMed Central

Kesari, Santosh; Schiff, David; Doherty, Lisa; Gigas, Debra C.; Batchelor, Tracy T.; Muzikansky, Alona; O’Neill, Alison; Drappatz, Jan; Chen-Plotkin, Alice S.; Ramakrishna, Naren; Weiss, Stephanie E.; Levy, Brenda; Bradshaw, Joanna; Kracher, Jean; Laforme, Andrea; Black, Peter McL.; Folkman, Judah; Kieran, Mark; Wen, Patrick Y.

2007-01-01

Preclinical evidence suggests that continuous low-dose daily (metronomic) chemotherapy may inhibit tumor endothelial cell proliferation (angiogenesis) and prevent tumor growth. This phase II study evaluated the feasibility of this antiangiogenic chemotherapy regimen in adults with recurrent malignant gliomas. The regimen consisted of low-dose etoposide (35 mg/m2 [maximum, 100 mg/day] daily for 21 days), alternating every 21 days with cyclophosphamide (2 mg/kg [maximum, 100 mg/day] daily for 21 days), in combination with daily thalidomide and celecoxib, in adult patients with recurrent malignant gliomas. Serum and urine samples were collected for measurement of angiogenic peptides. Forty-eight patients were enrolled (15 female, 33 male). Twenty-eight patients had glioblastoma multiforme (GBMs), and 20 had anaplastic gliomas (AGs). Median age was 53 years (range, 33–74 years), and median KPS was 70 (range, 60–100). Therapy was reasonably well tolerated in this heavily pretreated population. Two percent of patients had partial response, 9% had a minor response, 59% had stable disease, and 30% had progressive disease. For GBM patients, median progression-free survival (PFS) was 11 weeks, six-month PFS (6M-PFS) was 9%, and median overall survival (OS) was 21 weeks. For AG patients, median PFS was 14 weeks, 6M-PFS was 26%, and median OS was 41.5 weeks. In a limited subset of patients, serum and urine angiogenic peptides did not correlate with response or survival (p > 0.05). Although there were some responders, this four-drug, oral metronomic regimen did not significantly improve OS in this heavily pretreated group of patients who were generally not eligible for conventional protocols. While metronomic chemotherapy may not be useful in patients with advanced disease, further studies using metronomic chemotherapy combined with more potent antiangiogenic agents in patients with less advanced disease may be warranted. PMID:17452651

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

NASA Astrophysics Data System (ADS)

Jiang, Liqin; Li, Xuemin; Liu, Lingrong; Zhang, Qiqing

2013-02-01

Oral chemotherapy is a key step towards `chemotherapy at home', a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer.

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

PubMed Central

2013-01-01

Oral chemotherapy is a key step towards ‘chemotherapy at home’, a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer. PMID:23394588

Clonal evolution of chemotherapy-resistant urothelial carcinoma.

PubMed

Faltas, Bishoy M; Prandi, Davide; Tagawa, Scott T; Molina, Ana M; Nanus, David M; Sternberg, Cora; Rosenberg, Jonathan; Mosquera, Juan Miguel; Robinson, Brian; Elemento, Olivier; Sboner, Andrea; Beltran, Himisha; Demichelis, Francesca; Rubin, Mark A

2016-12-01

Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated urothelial carcinoma is characterized by intra-patient mutational heterogeneity, and the majority of mutations are not shared; (ii) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (iii) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways; and (iv) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime.

Chemotherapy extravasations: prevention, identification, management, and documentation.

PubMed

Gonzalez, Tulia

2013-02-01

The nurses' role in safe and effective practice of chemotherapy administration is paramount. The purpose of this article is to present nurses administering chemotherapy with evidence-based information useful in eliminating or reducing the severity of an injury from a chemotherapy extravasation. Nurse education is essential to prevent, recognize, manage, and document chemotherapy extravasations. The classification of the cytotoxic drug and its mechanism of action is useful when selecting the IV access device and also will direct the nurse's intervention to manage the injury. The Oncology Nursing Society's Chemotherapy and Biotherapy Guidelines and Recommendations for Practice and the drug manufacturer are the best sources offering pharmacologic and nonpharmacologic recommendations. The nurse's best ally in the prevention, prompt recognition, and management of an extravasation is the educated patient. Documenting chemotherapy extravasation is another important step to guide the treatment plan; therefore, the document must provide complete details and the extent of the event.

Second malignancies after chemotherapy and radiotherapy for Hodgkin disease.

PubMed

Chronowski, Gregory M; Wilder, Richard B; Levy, Larry B; Atkinson, Edward N; Ha, Chul S; Hagemeister, Fredrick B; Barista, Ibrahim; Rodriguez, Maria A; Sarris, Andreas H; Hess, Mark A; Cabanillas, Fernando; Cox, James D

2004-02-01

The purpose of this preliminary study was to determine the incidence of second malignancies after combined-modality therapy for adults with Hodgkin disease and relate it to the details of initial treatment. We retrospectively studied 286 patients ranging in age from 16 to 88 years with stage I or II Hodgkin disease who were treated between 1980 and 1995 with chemotherapy followed 3 to 4 weeks later by radiotherapy. Patients received a median of three cycles of induction chemotherapy. Mitoxantrone, vincristine, vinblastine, and prednisone was used in 161 cases, mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) in 67 cases, Adriamycin, bleomycin, vinblastine, and dacarbazine in 19 cases, lomustine, vinblastine, procarbazine, and prednisone/doxorubicin, bleomycin, dacarbazine, and lomustine in 18 cases, and other chemotherapeutic regimens in the remaining 21 cases. The median radiotherapy dose was 40 Gy given in 20 daily 2-Gy fractions. Median follow-up of surviving patients was 7.4 years. There were 2,230 person-years of observation. Significantly increased relative risks (RR) were observed for acute myeloid leukemia (RR, 69.3; 95% CI, 14.3-202.6) and melanoma (RR, 7.3; 95% CI, 1.5-21.3). The 5-, 10-, and 15-year actuarial risks of acute myeloid leukemia were 0.8%, 1.3%, and 1.3%, respectively. Patients treated with MOPP had the highest 15-year actuarial risk of leukemia (1.6%). The 5-, 10-, and 15-year actuarial risks of solid tumors were 1.9%, 9.3%, and 16.8%, respectively. Consolidative radiotherapy to both sides of the diaphragm resulted in a trend toward an increased risk of solid tumors relative to radiotherapy to only one side of the diaphragm (p = 0.08). In an effort to reduce the risk of second malignancies, we have stopped using the alkylating agents nitrogen mustard and procarbazine and elective paraaortic and splenic radiotherapy after chemotherapy.

Adjuvant chemotherapy for early female breast cancer: a systematic review of the evidence for the 2014 Cancer Care Ontario systemic therapy guideline

PubMed Central

Gandhi, S.; Fletcher, G.G.; Eisen, A.; Mates, M.; Freedman, O.C.; Dent, S.F.; Trudeau, M.E.

2015-01-01

Background The Program in Evidence-Based Care (pebc) of Cancer Care Ontario recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question “What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?” The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and human epidermal growth factor receptor 2 (her2)–directed therapy. Methods For the systematic review, the medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were “breast cancer” and “systemic therapy” (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (rcts), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. The Early Breast Cancer Trialists’ Collaborative Group meta-analyses encompassed many of the rcts found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Chemotherapy was reviewed mainly in three classes: anti-metabolite–based regimens (for example, cyclophosphamide–methotrexate–5-fluorouracil), anthracyclines, and taxane-based regimens. In general, single-agent chemotherapy is not recommended for the adjuvant treatment of breast cancer in any patient population. Anthracycline–taxane-based polychemotherapy regimens are, overall, considered superior to earlier-generation regimens and have the most significant impact on patient survival outcomes. Regimens with varying anthracycline and taxane doses and

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A quantitative chemotherapy genetic interaction map reveals new factors associated with PARP inhibitor resistance | Office of Cancer Genomics

Cancer.gov

Nearly every cancer patient is treated with chemotherapy yet our understanding of factors that dictate response and resistance to such agents remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells that charts the impact of knockdown of 625 cancer and DNA repair related genes on sensitivity to 29 drugs, covering all classes of cancer chemotherapeutics.

Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

PubMed

Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

2005-10-01

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy?

PubMed

Harrison, Louis; Blackwell, Kimberly

2004-01-01

Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO(2)] value < or =10 mmHg) is associated with lower overall and disease-free survival, greater recurrence, and less locoregional control in head and neck carcinoma, cervical carcinoma, and soft-tissue sarcoma. In view of the deleterious effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

PubMed

Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

2015-01-01

To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs.

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

PubMed Central

Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

2015-01-01

Purpose To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. Materials and methods This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. Results We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Conclusion Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs. PMID:26124681

Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.

PubMed

Moruno-Manchon, Jose F; Uzor, Ndidi-Ese; Kesler, Shelli R; Wefel, Jeffrey S; Townley, Debra M; Nagaraja, Archana Sidalaghatta; Pradeep, Sunila; Mangala, Lingegowda S; Sood, Anil K; Tsvetkov, Andrey S

2018-01-01

Doxorubicin, a commonly used anti-neoplastic agent, causes severe neurotoxicity. Doxorubicin promotes thinning of the brain cortex and accelerates brain aging, leading to cognitive impairment. Oxidative stress induced by doxorubicin contributes to cellular damage. In addition to mitochondria, peroxisomes also generate reactive oxygen species (ROS) and promote cell senescence. Here, we investigated if doxorubicin affects peroxisomal homeostasis in neurons. We demonstrate that the number of peroxisomes is increased in doxorubicin-treated neurons and in the brains of mice which underwent doxorubicin-based chemotherapy. Pexophagy, the specific autophagy of peroxisomes, is downregulated in neurons, and peroxisomes produce more ROS. 2-hydroxypropyl-β-cyclodextrin (HPβCD), an activator of the transcription factor TFEB, which regulates expression of genes involved in autophagy and lysosome function, mitigates damage of pexophagy and decreases ROS production induced by doxorubicin. We conclude that peroxisome-associated oxidative stress induced by doxorubicin may contribute to neurotoxicity, cognitive dysfunction, and accelerated brain aging in cancer patients and survivors. Peroxisomes might be a valuable new target for mitigating neuronal damage caused by chemotherapy drugs and for slowing down brain aging in general. Copyright © 2017 Elsevier Inc. All rights reserved.

Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma

PubMed Central

Florea, Ana-Maria; Varghese, Elizabeth; McCallum, Jennifer E.; Mahgoub, Safa; Helmy, Irfan; Varghese, Sharon; Gopinath, Neha; Sass, Steffen; Theis, Fabian J.; Reifenberger, Guido; Büsselberg, Dietrich

2017-01-01

Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i). In addition, the impact of pharmacological inhibition of [Ca2+]i-regulating proteins on neuroblastoma cell survival was studied. Treatment of neuroblastoma cells with increasing concentrations of CDDP (0.1−10 μM) or TOPO (0.1 nM−1 μM) induced cytotoxicity and increased apoptosis in a concentration- and time-dependent manner. Both drugs increased [Ca2+]i over time. Treatment with CDDP or TOPO also modified mRNA expression of selected genes encoding [Ca2+]i-regulating proteins. Differentially regulated genes included S100A6, ITPR1, ITPR3, RYR1 and RYR3. With FACS and confocal laser scanning microscopy experiments we validated their differential expression at the protein level. Importantly, treatment of neuroblastoma cells with pharmacological modulators of [Ca2+]i-regulating proteins in combination with CDDP or TOPO increased cytotoxicity. Thus, our results confirm an important role of calcium signaling in the response of neuroblastoma cells to chemotherapy and suggest [Ca2+]i modulation as a promising strategy for adjunctive treatment. PMID:28206967

Calcium-regulatory proteins as modulators of chemotherapy in human neuroblastoma.

PubMed

Florea, Ana-Maria; Varghese, Elizabeth; McCallum, Jennifer E; Mahgoub, Safa; Helmy, Irfan; Varghese, Sharon; Gopinath, Neha; Sass, Steffen; Theis, Fabian J; Reifenberger, Guido; Büsselberg, Dietrich

2017-04-04

Neuroblastoma (NB) is a pediatric cancer treated with poly-chemotherapy including platinum complexes (e.g. cisplatin (CDDP), carboplatin), DNA alkylating agents, and topoisomerase I inhibitors (e.g. topotecan (TOPO)). Despite aggressive treatment, NB may become resistant to chemotherapy. We investigated whether CDDP and TOPO treatment of NB cells interacts with the expression and function of proteins involved in regulating calcium signaling. Human neuroblastoma cell lines SH-SY5Y, IMR-32 and NLF were used to investigate the effects of CDDP and TOPO on cell viability, apoptosis, calcium homeostasis, and expression of selected proteins regulating intracellular calcium concentration ([Ca2+]i). In addition, the impact of pharmacological inhibition of [Ca2+]i-regulating proteins on neuroblastoma cell survival was studied. Treatment of neuroblastoma cells with increasing concentrations of CDDP (0.1-10 μM) or TOPO (0.1 nM-1 μM) induced cytotoxicity and increased apoptosis in a concentration- and time-dependent manner. Both drugs increased [Ca2+]i over time. Treatment with CDDP or TOPO also modified mRNA expression of selected genes encoding [Ca2+]i-regulating proteins. Differentially regulated genes included S100A6, ITPR1, ITPR3, RYR1 and RYR3. With FACS and confocal laser scanning microscopy experiments we validated their differential expression at the protein level. Importantly, treatment of neuroblastoma cells with pharmacological modulators of [Ca2+]i-regulating proteins in combination with CDDP or TOPO increased cytotoxicity. Thus, our results confirm an important role of calcium signaling in the response of neuroblastoma cells to chemotherapy and suggest [Ca2+]i modulation as a promising strategy for adjunctive treatment.

Advanced interstitial chemotherapy combined with targeted treatment of malignant glioma in rats by using drug-loaded nanofibrous membranes.

PubMed

Tseng, Yuan-Yun; Su, Chen-Hsing; Yang, Shun-Tai; Huang, Yin-Chen; Lee, Wei-Hwa; Wang, Yi-Chuan; Liu, Shou-Cheng; Liu, Shih-Jung

2016-09-13

Glioblastoma multiforme (GBM), the most prevalent and malignant form of a primary brain tumour, is resistant to chemotherapy. In this study, we concurrently loaded three chemotherapeutic agents [bis-chloroethylnitrosourea, irinotecan, and cisplatin; BIC] into 50:50 poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibres and an antiangiogenic agent (combretastatin) into 75:25 PLGA nanofibres [BIC and combretastatin (BICC)/PLGA]. The BICC/PLGA nanofibrous membranes were surgically implanted onto the brain surfaces of healthy rats for conducting pharmacodynamic studies and onto C6 glioma-bearing rats for estimating the therapeutic efficacy.The chemotherapeutic agents were rapidly released from the 50:50 PLGA nanofibres after implantation, followed by the release of combretastatin (approximately 2 weeks later) from the 75:25 PLGA nanofibres. All drug concentrations remained higher in brain tissues than in the blood for more than 8 weeks. The experimental results, including attenuated malignancy, retarded tumour growth, and prolonged survival in tumour-bearing rats, demonstrated the efficacy of the BICC/PLGA nanofibrous membranes. Furthermore, the efficacy of BIC/PLGA and BICC/PLGA nanofibrous membranes was compared. The BICC/PLGA nanofibrous membranes more efficiently retarded the tumour growth and attenuated the malignancy of C6 glioma-bearing rats. Moreover, the addition of combretastatin did not significantly change the drug release behaviour of the BIC/PLGA nanofibrous membranes. The present advanced and novel interstitial chemotherapy and targeted treatment provide a potential strategy and regimen for treating GBM.

Paradox of Prescribing Late Chemotherapy: Oncologists Explain.

PubMed

Bluhm, Minnie; Connell, Cathleen M; De Vries, Raymond G; Janz, Nancy K; Bickel, Kathleen E; Silveira, Maria J

2016-12-01

The value of chemotherapy for patients with cancer in the last weeks of life warrants examination. Late chemotherapy may not improve survival or quality of life but typically precludes hospice enrollment and may result in additional symptoms, increased use of other aggressive treatments, and worsening quality of life. Few studies have explored oncologists' rationales for administering chemotherapy near death. This study examines the self-reported factors that influence oncologists' decisions about late chemotherapy. In-depth individual interviews were conducted with 17 oncologists through a semistructured interview guide. Interviews were audio recorded and transcribed verbatim. Transcripts were coded and analyzed using conventional content analysis, a qualitative method that allows the detection and analysis of patterns in the data. Clinical factors take priority in determining late chemotherapy decisions when clear treatment choices exist. When clinical factors are ambiguous, emotion becomes a highly salient influence. Oncologists view late chemotherapy to be patient driven and use it to palliate emotional distress and maintain patient hope even when physical benefit is unexpected. Oncologists experience unique and difficult challenges when caring for dying patients, including emotionally draining communication, overwhelming responsibility for life/death, limitations of oncology to heal, and prognostic uncertainty. These challenges are also eased by offering late chemotherapy. The findings reveal a nuanced understanding of why oncologists find it difficult to refuse chemotherapy treatment for patients near death. Optimal end-of-life treatment decisions require supportive interventions and system change, both of which must take into account the challenges oncologists face.

Acupuncture and Reflexology for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer

PubMed Central

Ben-Horin, Idan; Kahan, Peretz; Ryvo, Larisa; Inbar, Moshe; Lev-Ari, Shahar; Geva, Ravit

2017-01-01

Background: Treatment of chemotherapy-induced peripheral neuropathy (CIPN), which affects approximately 30% to 40% of patients treated with neuropathy-causing agents, is mainly symptomatic. Currently available interventions are of little benefit. Study Design: This study was conducted as a retrospective analysis of the efficacy of acupuncture and reflexology in alleviating CIPN in breast cancer patients. Methods: Medical records of 30 consecutive breast cancer patients who received both chemotherapy and treatment for CIPN according to our Acupuncture and Reflexology Treatment for Neuropathy (ART-N) protocol between 2011 and 2012 were reviewed. Symptom severity was rated at baseline, during, and after treatment. Results: The records of 30 breast cancer patients who had been concomitantly treated with chemotherapy and ART-N for CIPN were retrieved. Two records were incomplete, leaving a total of 28 patients who were enrolled into the study. Twenty patients (71%) had sensory neuropathy, 7 (25%) had motor neuropathy, and 1 (4%) had both sensory and motor neuropathy. Only 2 (10%) of the 20 patients with grades 1 to 2 neuropathy still reported symptoms at 12 months since starting the ART-N protocol. All 8 patients who presented with grades 3 to 4 neuropathy were symptom-free at the 12-month evaluation. Overall, 26 patients (93%) had complete resolution of CIPN symptoms. Conclusion: The results of this study demonstrated that a joint protocol of acupuncture and reflexology has a potential to improve symptoms of CIPN in breast cancer patients. The protocol should be validated on a larger cohort with a control group. It also warrants testing as a preventive intervention. PMID:28150504

Acupuncture and Reflexology for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer.

PubMed

Ben-Horin, Idan; Kahan, Peretz; Ryvo, Larisa; Inbar, Moshe; Lev-Ari, Shahar; Geva, Ravit

2017-09-01

Treatment of chemotherapy-induced peripheral neuropathy (CIPN), which affects approximately 30% to 40% of patients treated with neuropathy-causing agents, is mainly symptomatic. Currently available interventions are of little benefit. This study was conducted as a retrospective analysis of the efficacy of acupuncture and reflexology in alleviating CIPN in breast cancer patients. Medical records of 30 consecutive breast cancer patients who received both chemotherapy and treatment for CIPN according to our Acupuncture and Reflexology Treatment for Neuropathy (ART-N) protocol between 2011 and 2012 were reviewed. Symptom severity was rated at baseline, during, and after treatment. The records of 30 breast cancer patients who had been concomitantly treated with chemotherapy and ART-N for CIPN were retrieved. Two records were incomplete, leaving a total of 28 patients who were enrolled into the study. Twenty patients (71%) had sensory neuropathy, 7 (25%) had motor neuropathy, and 1 (4%) had both sensory and motor neuropathy. Only 2 (10%) of the 20 patients with grades 1 to 2 neuropathy still reported symptoms at 12 months since starting the ART-N protocol. All 8 patients who presented with grades 3 to 4 neuropathy were symptom-free at the 12-month evaluation. Overall, 26 patients (93%) had complete resolution of CIPN symptoms. The results of this study demonstrated that a joint protocol of acupuncture and reflexology has a potential to improve symptoms of CIPN in breast cancer patients. The protocol should be validated on a larger cohort with a control group. It also warrants testing as a preventive intervention.

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

PubMed

Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

2015-05-01

The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment

NASA Astrophysics Data System (ADS)

Quinto, Christopher A.; Mohindra, Priya; Tong, Sheng; Bao, Gang

2015-07-01

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could

Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

DOE Office of Scientific and Technical Information (OSTI.GOV)

Porter, Holly A., E-mail: hport001@umaryland.edu; Molecular Medicine Program, University of Maryland School of Medicine, Baltimore, MD 21201; Carey, Gregory B., E-mail: gcarey@som.umaryland.edu

2012-08-15

The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression ofmore » IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. -- Highlights: Black-Right-Pointing-Pointer IRS1 enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. Black-Right-Pointing-Pointer This sensitivity is abrogated by the expression of IRS2. Black-Right-Pointing-Pointer Expressing IRS1 in 32D cells increased levels of Annexin A2. Black-Right-Pointing-Pointer Both IRS1 and Annexin A2 were located in cytoplasmic and membrane fractions. Black-Right-Pointing-Pointer Decreasing Annexin A2 in 32D-IRS1 cells abated their sensitivity to chemotherapy.« less

Activity of intraarterial carboplatin as a single agent in the treatment of newly diagnosed extremity osteosarcoma.

PubMed

Petrilli, A S; Kechichian, R; Broniscer, A; Garcia, R J; Tanaka, C; Francisco, J; Lederman, H; Odone Filho, V; Camargo, O P; Bruniera, P; Pericles, P; Consentino, E; Ortega, J A

1999-08-01

Chemotherapy has dramatically improved the rates of cure and survival of patients with localized and metastatic osteosarcoma. Nonetheless, the number of chemotherapeutic agents active against osteosarcoma is limited to doxorubicin, cisplatin, high-dose methotrexate, and ifosfamide. Carboplatin, a cisplatin analogue, has been tested as a single agent in patients with recurrent osteosarcoma or as part of multiagent chemotherapy in newly diagnosed patients. We tested the activity and toxicity of two cycles of intraarterial carboplatin as a "window therapy" (600 mg/m2 per cycle) in 33 consecutive patients with extremity osteosarcoma before the start of multiagent chemotherapy. Response was based on clinical (tumor diameter, local inflammatory signs, and range of motion) and radiological parameters (plain local films and arteriographic studies prior to drug administration). Patients' age ranged between 8 and 18 years (median age 13 years). Primary tumor originated from the femur (15 patients), tibia (10 patients), fibula (4 patients), humerus (3 patients), and calcaneus (1 patient). Only 7 patients (21%) had metastatic disease at diagnosis (5 in the lung and 2 in other bones). A favorable clinical and radiological response was documented in 81% and 73% of the patients, respectively. Clinical and radiological progression occurred in 12% and 9% of the patients, respectively. Seventeen of the patients remain alive and disease-free. Survival and event-free survival at 3 years for nonmetastatic patients are 71% (SE = 9%) and 65% (SE = 9%), respectively; for metastatic patients, the figures are 17% (SE = 15%) and 14% (SE = 13%), respectively. We conclude that carboplatin is an active agent in the treatment of newly diagnosed extremity osteosarcoma. Copyright 1999 Wiley-Liss, Inc.

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer.

PubMed

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Lee, Jung-Yun; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1-3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC.

Comparing Intra-Arterial Chemotherapy Combined With Intravesical Chemotherapy Versus Intravesical Chemotherapy Alone: A Randomised Prospective Pilot Study for T1G3 Bladder Transitional Cell Carcinoma After Bladder-Preserving Surgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Junxing, E-mail: Junxingchen@hotmail.com; Yao, Zhijun, E-mail: yaozhijun1985@qq.com; Qiu, Shaopeng, E-mail: qiushp@mail.sysu.edu.cn

Purpose: To compare the efficacy of intra-arterial chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder transitional cell carcinoma (BTCC) followed by bladder-preserving surgery. Materials and Methods: Sixty patients with T1G3 BTCC were randomly divided into two groups. After bladder-preserving surgery, 29 patients (age 30-80 years, 24 male and 5 female) received intra-arterial chemotherapy in combination with intravesical chemotherapy (group A), whereas 31 patients (age 29-83 years, 26 male and 5 female) were treated with intravesical chemotherapy alone (group B). Twenty-nine patients were treated with intra-arterial epirubicin (50 mg/m{sup 2}) + cisplatin (60 mg/m{sup 2}) chemotherapy 2-3more » weeks after bladder-preserving surgery once every 4-6 weeks. All of the patients received the same intravesical chemotherapy: An immediate prophylactic was administered in the first 6 h. After that, therapy was administered one time per week for 8 weeks and then one time per month for 8 months. The instillation drug was epirubicin (50 mg/m{sup 2}) and lasted for 30-40 min each time. The end points were tumour recurrence (stage Ta, T1), tumour progression (to T2 or greater), and disease-specific survival. During median follow-up of 22 months, the overall survival rate, tumour-specific death rate, recurrence rate, progression rate, time to first recurrence, and adverse reactions were compared between groups. Results: The recurrence rates were 10.3 % (3 of 29) in group A and 45.2 % (14 of 31) in group B, and the progression rates were 0 % (0 of 29) in group A and 22.6 % (7 of 31) in group B. There was a significant difference between the two groups regarding recurrence (p = 0.004) and progression rates (p = 0.011). Median times to first recurrence in the two groups were 15 and 6.5 months, respectively. The overall survival rates were 96.6 and 87.1 %, and the tumour-specific death rates were 0 % (0 of 29) and 13.5 % (4

Peripheral arteriovenous fistula as vascular access for long-term chemotherapy.

PubMed

Kovalyov, Oleksiy O; Kostyuk, Oleksandr G; Tkachuk, Tetyana V

To provide long-term vascular access in clinical oncology peripheral forearm veins (up to 95% of patients in Ukraine), central venous access and "complete implanted vascular systems" are used most often. Many oncology patients have contraindications to catheterization of superior vena cava. Besides, exploitation of central veins is associated with potential technical and infectious complications. The aim - to study short-term and long-term results of arteriovenous fistula exploitation as vascular access for continuous anticancer therapy. Peripheral venous bed status in 41 oncology patients taking long-term chemotherapy treatment is analyzed in the article. Doppler sonography, morphologic and immune histochemical analyses were used in the study. Doppler sonography found qualitative and quantitative changes in forearm veins at different time periods after initiation of chemotherapy in the majority of patients. The major morphologic manifestations of venous wall damage were chemical phlebitis, local or extended hardening of venous wall, venous thrombosis and extravasations with necrosis and subsequent paravasal tissue sclerosis. Alternative vascular access created in 12 patients completely met the adequacy criteria (safety, multiple use, longevity, realization of the designed therapy program). The conclusion was made about inapplicability of forearm veins for long-term administration of cytostatic agents. If it is impossible to use central veins, arteriovenous fistula can become an alternative vascular access.

The combination of bortezomib with chemotherapy to treat relapsed/refractory acute lymphoblastic leukaemia of childhood.

PubMed

Bertaina, Alice; Vinti, Luciana; Strocchio, Luisa; Gaspari, Stefania; Caruso, Roberta; Algeri, Mattia; Coletti, Valentina; Gurnari, Carmelo; Romano, Mariateresa; Cefalo, Maria Giuseppina; Girardi, Katia; Trevisan, Valentina; Bertaina, Valentina; Merli, Pietro; Locatelli, Franco

2017-02-01

Achieving complete remission (CR) in childhood relapsed/refractory acute lymphoblastic leukaemia (ALL) is a difficult task. Bortezomib, a proteasome inhibitor, has in vitro activity against ALL blasts. A phase I-II trial, reported by the Therapeutic Advances in Childhood Leukaemia and Lymphoma (TACL) consortium, demonstrated that bortezomib with chemotherapy has acceptable toxicity and remarkable activity in patients with relapsed ALL failing 2-3 previous regimens. We evaluated bortezomib in combination with chemotherapy in 30 and 7 children with B-cell precursor (BCP) and T-cell ALL, respectively. Bortezomib (1·3 mg/m 2 /dose) was administered intravenously on days 1, 4, 8, and 11. Chemotherapy agents were the same as those used in the TACL trial, consisting of dexamethasone, doxorubicin, vincristine and pegylated asparaginase. Three patients (8·1%) died due to infections. Twenty-seven patients (72·9%) achieved CR or CR with incomplete platelet recovery (CRp). Fourteen had minimal residual disease (MRD) lower than 0·1%. Twenty-two of 30 BCP-ALL patients (73·3%) and 5/7 patients (71%) with T-cell ALL achieved CR/CRp. The 2-year overall survival (OS) is 31·3%; CR/CRp patients with an MRD response had a remarkable 2-year OS of 68·4%. These data confirm that the combination of bortezomib with chemotherapy is a suitable/effective option for childhood relapsed/refractory ALL. © 2017 John Wiley & Sons Ltd.

Oncogenic RAS Enables DNA Damage- and p53-Dependent Differentiation of Acute Myeloid Leukemia Cells in Response to Chemotherapy

PubMed Central

Meyer, Mona; Rübsamen, Daniela; Slany, Robert; Illmer, Thomas; Stabla, Kathleen; Roth, Petra; Stiewe, Thorsten

2009-01-01

Acute myeloid leukemia (AML) is a clonal disease originating from myeloid progenitor cells with a heterogeneous genetic background. High-dose cytarabine is used as the standard consolidation chemotherapy. Oncogenic RAS mutations are frequently observed in AML, and are associated with beneficial response to cytarabine. Why AML-patients with oncogenic RAS benefit most from high-dose cytarabine post-remission therapy is not well understood. Here we used bone marrow cells expressing a conditional MLL-ENL-ER oncogene to investigate the interaction of oncogenic RAS and chemotherapeutic agents. We show that oncogenic RAS synergizes with cytotoxic agents such as cytarabine in activation of DNA damage checkpoints, resulting in a p53-dependent genetic program that reduces clonogenicity and increases myeloid differentiation. Our data can explain the beneficial effects observed for AML patients with oncogenic RAS treated with higher dosages of cytarabine and suggest that induction of p53-dependent differentiation, e.g. by interfering with Mdm2-mediated degradation, may be a rational approach to increase cure rate in response to chemotherapy. The data also support the notion that the therapeutic success of cytotoxic drugs may depend on their ability to promote the differentiation of tumor-initiating cells. PMID:19890398

Excellent response to chemotherapy post immunotherapy

PubMed Central

Dwary, Ashish D.; Master, Samip; Patel, Abhishek; Cole, Constance; Mansour, Richard; Mills, Glenn; Koshy, Nebu; Peddi, Prakash; Burton, Gary; Hammoud, Dalia; Beedupalli, Kavitha

2017-01-01

Introduction Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines. Here we present a case series of 6 patients who progressed on immunotherapy with immune checkpoint inhibitors after initial modality of treatment (chemotherapy/radiation), subsequently received chemotherapy with excellent response. Methods We have a cohort of six patients who had disease progression on second line Immunotherapy for solid or hematological malignancies and had ECOG < 2. All these patients received third line salvage chemotherapy. Three patients had metastatic head and neck cancer, 2 had non-small cell lung cancer (NSCLC), and one had T -cell rich B- cell lymphoma. Prior review and approval were obtained from our institutional review board. Results All patients had an excellent response to chemotherapy in third line setting, after immune checkpoint inhibitors and most of them achieved a complete response. Conclusion Targeting cancer with chemotherapy after failure of immunotherapy is a valid option and can lead to better response rates and PFS which may lead to OS. This effect may be secondary to immunotherapy removing the inhibition exerted by tumor cells or other immune cells initially followed by cytotoxic chemotherapy mediated killing of tumor cells. PMID:29207685

Adjuvant chemotherapy for endometrial cancer after hysterectomy

PubMed Central

Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

2014-01-01

Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

Post chemotherapy extravasation injuries: Hypogastric flap for reconstruction of wounds over dorsum of hand.

PubMed

Salunke, Abhijeet Ashok; Nambi, G I; Sudhakar, N

2015-01-01

Management of extravasation injuries over the dorsum of hand after administration of chemotherapeutic agents. To study the results of hypogastric flap reconstruction in chemotherapy extravasation wounds over dorsum of hand. Retrospective study. At our center over 3-years period, 32 patients were treated for chemotherapy extravasation wounds. Out of these 32 patients, seven had wound over dorsum of hand. There were five males and two females, and their mean age was 45 years (range, 19 - 64 years). These patients with wound over the dorsum of hand were treated with multiple debridements and hypogastric flap reconstruction. The mean interval between extravasation wound and surgical treatment was 6.28 days (range, 4 - 10). The mean size of extravasation wound defect was 14 × 8 (range, 12 × 7 to 18 × 8). Non-dominant hand was involved in six patients and dominant hand in one patient. In four patients, the hypogastric flap was supplemented with skin graft. The hypogastric flap settled well in all patients and enabled a good wound cover. Complete division of the flap and final insetting was done under local anesthesia after 3 weeks; this was followed by limb mobilization exercises. Contour difference over the dorsum of hand was present in all the cases. The range of movement of the hand was functionally restricted in one patient. No patient in current series developed wound infection. Hypogastric flap is a reliable flap to cover wound over dorsum of hand after extravasation of chemotherapeutic agents.

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 ...

Schedule-Dependent Antiangiogenic and Cytotoxic Effects of Chemotherapy on Vascular Endothelial and Retinoblastoma Cells.

PubMed

Winter, Ursula; Mena, Hebe A; Negrotto, Soledad; Arana, Eloisa; Pascual-Pasto, Guillem; Laurent, Viviana; Suñol, Mariona; Chantada, Guillermo L; Carcaboso, Angel M; Schaiquevich, Paula

2016-01-01

topotecan lead to significantly lower tumor volumes compared to conventional treatment after 14 days of treatment (p<0.05). Continuous exposure to melphalan or topotecan increased the chemosensitivity of retinoblastoma and endothelial cells to both chemotherapy agents with lower IC50 values compared to short-term treatment. These findings were validated in an in vivo model. None of the dosing modalities induced multidrug resistance mechanisms while apoptosis was the mechanism of cell death after both treatment schedules. Metronomic chemotherapy may be a valid option for retinoblastoma treatment allowing reductions of the daily dose.

Managing Chemotherapy Side Effects: Bleeding Problems

MedlinePlus

... C ancer I nstitute Managing Chemotherapy Side Effects Bleeding Problems “My nurse said that chemotherapy could make ... with a clean cloth. Keep pressing until the bleeding stops. If you bruise: Put ice on the ...

Chemotherapy - what to ask your doctor

MedlinePlus

... More Brain tumor - children Brain tumor - primary - adults Breast cancer Chemotherapy Colon cancer Hodgkin lymphoma Lung cancer - small cell Non-Hodgkin lymphoma Ovarian cancer Testicular cancer Patient Instructions After chemotherapy - discharge Bleeding during cancer treatment ...

Treatment Satisfaction and Adherence to Oral Chemotherapy in Patients With Cancer.

PubMed

Jacobs, Jamie M; Pensak, Nicole A; Sporn, Nora J; MacDonald, James J; Lennes, Inga T; Safren, Steven A; Pirl, William F; Temel, Jennifer S; Greer, Joseph A

2017-05-01

Although patients with cancer overwhelming prefer oral to intravenous chemotherapy, little is known about adherence to oral agents. We aimed to identify the rates and correlates of adherence in patients with diverse malignancies. Ninety patients with chronic myeloid leukemia or metastatic renal cell carcinoma, non-small-cell lung cancer, or breast cancer enrolled in this prospective, single-group, observational study of medication-taking behaviors. Adherence was measured via self-report and with an electronic pill cap (Medication Event Monitoring System cap). Patients completed surveys regarding symptom distress, mood, quality of life, cancer-specific distress, and satisfaction with clinician communication and treatment at baseline and 12-week follow-up. As measured by the Medication Event Monitoring System, patients took, on average, 89.3% of their prescribed oral chemotherapy over the 12 weeks. One quarter of the sample was less than 90% adherent, and women were more adherent than men (mean difference, 9.59%; SE difference, 4.50%; 95% CI, -18.65 to -0.52; P = .039). Improvements in patient symptom distress (B = -0.79; 95% CI, -1.41 to -0.18), depressive symptoms (B = -1.57; 95% CI, -2.86 to -0.29), quality of life (B = 0.38; 95% CI ,0.07 to 0.68), satisfaction with clinician communication and treatment (B = 0.73; 95% CI, 0.49 to 0.98), and perceived burden to others (B = -1.28; 95% CI, -2.20 to -0.37) were associated with better adherence. In a multivariate model, improved treatment satisfaction (B = 0.71; 95% CI, 0.48 to 0.94) and reduced perceived burden (B = -0.92; 95% CI, -1.76 to -0.09) were the strongest indicators of better adherence. Women and patients who reported increased treatment satisfaction and reduced burden to others were more adherent to oral chemotherapy. Interventions that help patients improve communication with clinicians and reduce burden may optimize oral chemotherapy adherence.

Adjuvant chemotherapy for rectal cancer: Is it needed?

PubMed Central

Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

2015-01-01

Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

Impact of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy cycles on survival of patients with advanced-stage ovarian cancer

PubMed Central

Chung, Young Shin; Kim, Yun-Ji; Lee, Inha; Nam, Eun Ji; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae

2017-01-01

Background There is currently no consensus regarding the optimal number of chemotherapy cycles to be administered before and after interval debulking surgery (IDS) in patients with advanced ovarian cancer. This study aimed to evaluate the impact of the number of neoadjuvant chemotherapy (NAC) and postoperative adjuvant chemotherapy (POAC) cycles on the survival of patients with advanced ovarian cancer undergoing NAC/IDS/POAC. Methods We retrospectively reviewed data from 203 patients who underwent NAC/IDS/POAC at Yonsei Cancer Hospital between 2006 and 2016. All patients underwent taxane plus carboplatin chemotherapy for NAC and POAC. The patient outcomes were analyzed according to the number of NAC, POAC, and total chemotherapy (NAC+POAC) cycles. Results Patients who received fewer than 6 cycles of total chemotherapy (n = 8) had poorer progression-free survival (PFS) and overall survival (OS) than those completing at least 6 cycles (p = 0.005 and p<0.001, respectively). Among patients who completed at least 6 cycles of total chemotherapy (n = 189), Kaplan-Meier analysis revealed no significant difference in either PFS or OS according to the number of NAC cycles (1–3 vs. ≥4; p = 0.136 and p = 0.267, respectively). Among patients who experienced complete remission after 3 cycles of POAC (n = 98), the addition of further POAC cycles did not improve the PFS or OS (3 vs. ≥4; p = 0.641 and p = 0.104, respectively). Conclusion IDS after 4 cycles of NAC may be a safe and effective option when completing 6 cycles of total chemotherapy. Furthermore, the addition of more than 3 cycles of POAC does not appear to influence the survival of patients achieving completion remission after 3 cycles of POAC. PMID:28873393

Neoadjuvant chemotherapy for radioinduced osteosarcoma of the extremity: The Rizzoli experience in 20 cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bacci, Gaetano; Longhi, Alessandra; Forni, Cristiana R.N.

2007-02-01

Purpose: Evaluate treatment and outcome of 20 patients with radioinduced osteosarcoma (RIO). Because of previous primary tumor treatment, RIO protocols were different from others we used for non-RIO. Patients and Methods: Between 1983 and 1998, we treated 20 RIO patients, ages 4-36 years (mean 16 years), with chemotherapy (two cycles before surgery, three postoperatively). The first preoperative cycle consisted of high-dose Methotrexate (HDMTX)/Cisplatinum (CDP)/Adriamycin (ADM) and the second of HDMTX/CDP/Ifosfamide (IFO). The three postoperative treatments were performed with cycles of MTX/CDP; IFO was used as single agent per cycle repeated three times. Results: Two patients received palliative treatment because theirmore » osteosarcoma remained unresectable after preoperative chemotherapy. The remaining 18 patients had surgery (7 amputations, 11 resections); histologic response to preoperative chemotherapy was good in 8 patients, poor in 10. At a mean follow-up of 11 years (range, 7-22 years), 9 patients remained continuously disease-free, 10 died from osteosarcoma and 1 died from a third neoplasm (myeloid acute leukemia). These results are not significantly different from those achieved in 754 patients with conventional osteosarcoma treated in the same period with protocols used for conventional treatment. However, this later group had an 18% 3-year event-free survival after treatment of relapse vs. 0% in the RIO group. Conclusion: Treated with neoadjuvant chemotherapy RIO seem to have an outcome that is not significantly different from that of comparable patients with conventional primary high grade osteosarcoma (5-year event-free survival: 40% vs. 60%, p = NS; 5-year overall survival 40% vs. 67%, p < 0.00008.« less

Will novel agents for ALL finally change the natural history?

PubMed

Douer, Dan

2014-01-01

Pediatric acute lymphoblastic leukemia (ALL) cure rates have markedly improved over the past years to approximately 85%, but remain at 40%-50% in adults. Redefining current adult chemotherapy regimens is likely to improve the natural course of the disease, but new agents are needed. Immunotherapy approaches for pre-B ALL are in the forefront of research on novel agents; in particular, advances are being made in manipulating autologous T cells either by infusion of a bifunctional antibody (eg, blinatumomab) or by ex vivo genetic modification of chimeric antigen receptors (CARs). The natural course of Philadelphia positive ALL has already improved by targeting ABL/BCR1. Other mutated genes are being discovered and novel small molecules that target their products are being studied in clinical trials. Finally, ALL is a heterogeneous disease and novel agents are likely to impact the natural course of smaller populations of biologically defined ALL subtypes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Use of Neoadjuvant Chemotherapy Plus Molecular Targeted Therapy in Colorectal Liver Metastases: A Systematic Review and Meta-analysis.

PubMed

Sabanathan, Dhanusha; Eslick, Guy D; Shannon, Jenny

2016-12-01

Surgery remains the standard of care for patients with colorectal liver metastases (CLMs), with a 5-year survival rate approaching 35%. Perioperative chemotherapy confers a survival benefit in selected patients with CLMs. The use of molecular targeted therapy combined with neoadjuvant chemotherapy for CLMs, however, remains controversial. We reviewed the published data on combination neoadjuvant chemotherapy and molecular targeted therapy for resectable and initially unresectable CLMs. A literature search of the Medline and PubMed databases was conducted to identify studies of neoadjuvant chemotherapy plus molecular targeted therapy in the management of resectable or initially unresectable CLMs. We calculated the pooled proportion and 95% confidence intervals using a random effects model for the relationship of the combination neoadjuvant treatment on the overall response rate and performed a systematic review of all identified studies. The analysis was stratified according to the study design. The data from 11 studies of 908 patients who had undergone systemic chemotherapy plus targeted therapy for CLM were analyzed. The use of combination neoadjuvant therapy was associated with an overall response rate of 68% (95% confidence interval, 63%-73%), with significant heterogeneity observed in the studies (I 2  = 89.35; P < .001). Of the 11 studies, 4 used a combination that included oxaliplatin, 2 included irinotecan, and 5 included a combination of both. Also, 7 studies used cetuximab and 4 bevacizumab. The overall progression-free survival was estimated at 14.4 months. Current evidence suggests that neoadjuvant chemotherapy plus molecular targeted agents for CLM confers high overall response rates. Combination treatment might also increase the resectability rates in initially unresectable CLM. Further studies are needed to examine the survival outcomes, with a focus on the differential role of molecular targeted therapy in the neoadjuvant versus adjuvant setting

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis

PubMed Central

Morrow, Gary R; Schwartzberg, Lee; Barbour, Sally Y; Ballinari, Gianluca; Thorn, Michael D; Cox, David

2015-01-01

Background No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, particularly delayed nausea. Objective To compare the efficacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. Methods Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. Results Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. Limitations This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be influenced by interindividual variability. Conclusion Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable

Long-term follow up of high-dose chemotherapy with autologous stem cell rescue in adults with Ewing tumor.

PubMed

Laurence, Valérie; Pierga, Jean-Yves; Barthier, Sophie; Babinet, Antoine; Alapetite, Claire; Palangié, Thao; de Pinieux, Gonzagues; Anract, Philippe; Pouillart, Pierre

2005-06-01

Ewing tumors remain of poor prognosis, with 5-year overall survival of 55% to 65% in localized patients and not exceeding 25% in primarily metastatic disease. Several reports, mainly in children, have reported that some patients with poor-risk Ewing tumors may benefit from high-dose chemotherapy (HDCT) with autologous stem cell rescue. This retrospective study analyzed 46 patients treated in our institution between 1987 and 2000 for localized or primary metastatic Ewing tumors by HDCT followed by stem cell rescue. Median follow up was 7.1 years. Median age was 21 years (range, 15-46 years). Twenty-two percent of patients had metastases at diagnosis. The tumor site was axial in 56% of patients. Median tumor size was 9.5 cm. The treatment regimen consisted of induction chemotherapy, local treatment, maintenance chemotherapy, and consolidation HDCT based on alkylating agents. No toxic death was observed in the intensive therapy phase. Five-year overall survival and progression-free survival were 63 +/- 7.7% and 47 +/- 7.6%, respectively. Pejorative prognostic factors in this population were metastases at diagnosis (5-year overall survival 34% vs.71%, P = 0.017) and poor pathologic response (5-year overall survival 44% vs.77%, P = 0.03). This retrospective study shows a high long-term survival rate with high-dose chemotherapy in adults.

Successful treatment of ovarian cancer with apatinib combined with chemotherapy: A case report.

PubMed

Zhang, Mingzi; Tian, Zhongkai; Sun, Yehong

2017-11-01

The standard treatment for ovarian cancer is chemotherapy with 2 drugs (taxanes and platinum drugs). However, the traditional combination of the 2 drugs has many adverse effects (AEs) and the cancer cells will quickly become resistant to the drugs. Apatinib is a small-molecule antiangiogenic agent which has shown promising therapeutic effects against diverse tumor types, but it still remains unknown whether apatinib has an antitumor effect in patients with ovarian cancer. Herein, we present a successfully treated case of ovarian cancer using chemotherapy and apatinib, in order to demonstrate the effectiveness of this new combined regimen in ovarian cancer. A 51-year-old Chinese woman presented with ovarian cancer >4.5 years. The disease and the cancer antigen 125 (CA-125) had been controlled well by surgical treatment and following chemotherapy. However, the drugs could not control the disease anymore as the CA-125 level was significantly increasing. Ovarian cancer. The patient was treated with apatinib combined with epirubicin. Apatinib was administered orally, at an initial daily dose of 500 mg, and was then reduced to 250 mg qd after the appearance of intolerable hand-foot syndrome (HFS) and oral ulcer. Then, the oral ulcer disappeared and the HFS was controlled by dose adjustment, oral vitamin B6, and hand cream application. The CA-125 reverted to the normal value after treatment with the new regimen. Magnetic resonance imaging showed that the original tumor lesions had disappeared. Apatinib monotherapy as maintenance therapy was then used to successfully control the cancer with a complete response. Our study is the first, to our knowledge, to report the therapeutic effects of apatinib and epirubicin on ovarian cancer. Apatinib combined with chemotherapy and apatinib monotherapy as maintenance therapy could be a new therapeutic strategy for ovarian cancer, especially adenocarcinomas.

Selection of chemotherapy for glioblastoma expressing O6-methylguanine-DNA methyltransferase

PubMed Central

IWADATE, YASUO; MATSUTANI, TOMOO; HASEGAWA, YUZO; SHINOZAKI, NATSUKI; OIDE, TAKASHI; TANIZAWA, TORU; NAKATANI, YUKIO; SAEKI, NAOKATSU; FUJIMOTO, SHUICHI

2010-01-01

The therapeutic benefit of nitrosoureas or temozolomide for glioblastoma is limited mainly by O6-methylguanine-DNA methyltransferase (MGMT) expression. The aim of this study was to evaluate the effectiveness of various anticancer drugs for MGMT-positive glioblastoma. Seventy-four glioblastoma patients were administered various anticancer drugs according to drug sensitivity testing. For the individualization, drug-induced apoptosis was quantified by flow cytometry in the primary culture of surgically resected tumor cells. The MGMT protein expression was analyzed by immunohistochemistry. The median survival of the patients receiving the individualized chemotherapy was 19.4 months (95% CI, 15.9–22.1). The patients with negative MGMT immunostaining had significantly longer survival than those with positive MGMT immunostaining [median survival, 22.3 months (95% CI, 17.6–27.0) vs. 15.1 months (95% CI, 13.4–16.8); p=0.0188]. For MGMT-positive tumors, the platinum agents and the taxanes were more frequently selected for administration than the other categories of anticancer agents. The patient survival period of MGMT-positive glioblastomas treated with the platinum agents or the taxanes [median survival, 20.1 months (95% CI, 18.0–22.7)] was significantly longer than that of MGMT-positive tumors treated with nitrosoureas (p=0.0026), and was equivalent to that of MGMT-negative glioblastomas (p=0.3047). These results suggest that the platinum agents and the taxanes offer the best probability to be effective against immunohistochemically MGMT-positive glioblastomas. PMID:23136592

Effect of the lymphocyte-to-monocyte ratio on the clinical outcome of chemotherapy administration in advanced melanoma patients.

PubMed

Leontovich, Alexey A; Dronca, Roxana S; Nevala, Wendy K; Thompson, Michael A; Kottschade, Lisa A; Ivanov, Leonid V; Markovic, Svetomir N

2017-02-01

Skin cancer affects more individuals in the USA than any other malignancy and malignant melanoma is particularly deadly because of its metastatic potential. Melanoma has been recognized as one of the most immunogenic malignancies; therefore, understanding the mechanisms of tumor-immune interaction is key for developing more efficient treatments. As the tumor microenvironment shows an immunosuppressive action, immunotherapeutic agents promoting endogenous immune response to cancer have been tested (interleukin-2, anticytotoxic-T-lymphocyte-associated antigen 4, and antiprogrammed cell death protein 1 monoclonal antibodies) as well as combinations of cytotoxic chemotherapy agents and inhibitors of angiogenesis (taxol/carboplatin/avastin). However, clinical outcomes are variable, with only a minority of patients achieving durable complete responses. The variability of immune homeostasis, which may be more active or more tolerant at any given time, in cancer patients and the interaction of the immune system with the tumor could explain the inconsistency in clinical outcomes among these patients. Recently, the role of the lymphocyte-to-monocyte-ratio (LMR) in the peripheral blood has been investigated and has been proven to be an independent predictor of survival in different hematological malignancies and in solid tumors. In melanoma, our group has validated the significance of LMR as a predictor of relapse after resection of advanced melanoma. In this study, we examined the dynamics in the immune system of patients with advanced melanoma by performing serial multiday concentration measurements of cytokines and immune cell subsets in the peripheral blood. The analysis of outcomes of chemotherapy administration as related to LMR on the day of treatment initiation showed that progression-free survival was improved in the patients who received chemotherapy on the day when LMR was elevated.

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

PubMed

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Effects of exercise during chemotherapy on chemotherapy-induced peripheral neuropathy: a multicenter, randomized controlled trial.

PubMed

Kleckner, Ian R; Kamen, Charles; Gewandter, Jennifer S; Mohile, Nimish A; Heckler, Charles E; Culakova, Eva; Fung, Chunkit; Janelsins, Michelle C; Asare, Matthew; Lin, Po-Ju; Reddy, Pavan S; Giguere, Jeffrey; Berenberg, Jeffrey; Kesler, Shelli R; Mustian, Karen M

2018-04-01

Over half of all cancer patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), which includes numbness, tingling, pain, cold sensitivity, and motor impairment in the hands and feet. CIPN is a dose-limiting toxicity, potentially increasing mortality. There are no FDA-approved drugs to treat CIPN, and behavioral interventions such as exercise are promising yet understudied. This secondary analysis of our nationwide phase III randomized controlled trial of exercise for fatigue examines (1) effects of exercise on CIPN symptoms, (2) factors that predict CIPN symptoms, and (3) factors that moderate effects of exercise on CIPN symptoms. Cancer patients (N = 355, 56 ± 11 years, 93% female, 79% breast cancer) receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy were randomized to chemotherapy or chemotherapy plus Exercise for Cancer Patients (EXCAP©®). EXCAP is a standardized, individualized, moderate-intensity, home-based, six-week progressive walking and resistance exercise program. Patients reported CIPN symptoms of numbness and tingling and hot/coldness in hands/feet (0-10 scales) pre- and post-intervention. We explored baseline neuropathy, sex, age, body mass index, cancer stage, and cancer type as possible factors associated with CIPN symptoms and exercise effectiveness. Exercise reduced CIPN symptoms of hot/coldness in hands/feet (-0.46 units, p = 0.045) and numbness and tingling (- 0.42 units, p = 0.061) compared to the control. Exercise reduced CIPN symptoms more for patients who were older (p = 0.086), male (p = 0.028), or had breast cancer (p = 0.076). Exercise appears to reduce CIPN symptoms in patients receiving taxane-, platinum-, or vinca alkaloid-based chemotherapy. Clinicians should consider prescribing exercise for these patients. Clinical Trials.gov , # NCT00924651, http://www.clinicaltrials.gov .

Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

PubMed Central

Sugarbaker, Paul H.; Bijelic, Lana

2012-01-01

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC) was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement. PMID:22888340

Defining the impact of the use of granulocyte colony stimulating factors on the incidence of chemotherapy-induced neutropenia in patients with gynecologic malignancies.

PubMed

Julius, Justin M; Hammerstrom, Aimee; Wei, Caimiao; Rajesh, Raeshmma; Bodurka, Diane C; Kurian, Shiney; Smith, Judith A

2017-03-01

Purpose The objectives of this study were to characterize the incidence of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) with specific chemotherapy agents commonly used in the treatment of gynecologic malignancies, as well as defining the impact of granulocyte colony stimulating factors (G-CSF) on the prevention of CIN and FN in this patient population. Methods This retrospective analysis was conducted from a database of 635 gynecologic cancer patients who received chemotherapy between 1 September 2007 and 31 August 2008. A logistic regression analysis was conducted to determine the impact of potential covariates on the overall incidence of CIN. Results Overall, 28.3% of patients experienced CIN with one or more cycles chemotherapy, and 13.1% had treatment delays or dose reduction associated with CIN. The use of G-CSF prior to administration of chemotherapy resulted in a decrease in the incidence of CIN from 29.8% to 19.6% compared to no G-CSF use. No difference was observed in number of treatment delays or dose reductions in the 46 (7.2%) of gynecologic cancer patients that received G-CSF prophylaxis. Multivariate analysis found that both age and the number of current cycles jointly may predict risk of CIN. Conclusions Patients with gynecologic malignancies appear to be at a higher risk of development of neutropenia when treated with chemotherapy. The proactive use of G-CSF did decrease the risk of CIN by over 30%. Prospective study is warranted to determine the impact of G-CSF to reduce CIN in patients with gynecologic malignancies receiving chemotherapy.

Role of intercellular communications in breast cancer multicellular tumor spheroids after chemotherapy.

PubMed

Oktem, G; Bilir, A; Ayla, S; Yavasoglu, A; Goksel, G; Saydam, G; Uysal, A

2006-01-01

Tumor heterogeneity is an important feature that is especially involved in tumor aggressiveness. Multicellular tumor spheroids (MTS) may provide some benefits in different steps for investigation of the aggregation, organization, differentiation, and network formation of tumor cells in 3D space. This model offers a unique opportunity for improvements in the capability of a current strategy to detect the effect of an appropriate anticancer agent. The aim of this study was to investigate the cellular interactions and morphological changes following chemotherapy in a 3D breast cancer spheroid model. Distribution of the gap junction protein "connexin-43" and the tight junction protein "occludin" was investigated by immunohistochemistry. Cellular interactions were examined by using transmission and scanning electron microscopies as well as light microscopy with Giemsa staining after treating cells with doxorubicin, docetaxel, and doxorubicin/docetaxel combination. Statistical analyses showed significant changes and various alterations that were observed in all groups; however, the most prominent effect was detected in the doxorubicin/docetaxel combination group. Distinct composition as a vessel-like structure and a pseudoglandular pattern of control spheroids were detected in drug-administered groups. Immunohistochemical results were consistent with the ultrastructural changes. In conclusion, doxorubicin/docetaxel combination may be more effective than the single drug usage as shown in a 3D model. The MTS model has been found to be an appropriate and reliable method for the detection of the changes in the expression of cellular junction proteins as well as other cellular proteins occurring after chemotherapy. The MTS model can be used to validate the effects of various combinations or new chemotherapeutic agents as well as documentation of possible mechanisms of new drugs.

Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

PubMed

Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

2017-08-01

Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

Update on adjuvant chemotherapy for early breast cancer.

PubMed

Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

2014-01-01

Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come.

Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial.

PubMed

Ferreri, Andrés J M; Cwynarski, Kate; Pulczynski, Elisa; Fox, Christopher P; Schorb, Elisabeth; La Rosée, Paul; Binder, Mascha; Fabbri, Alberto; Torri, Valter; Minacapelli, Eleonora; Falautano, Monica; Ilariucci, Fiorella; Ambrosetti, Achille; Roth, Alexander; Hemmaway, Claire; Johnson, Peter; Linton, Kim M; Pukrop, Tobias; Sønderskov Gørløv, Jette; Balzarotti, Monica; Hess, Georg; Keller, Ulrich; Stilgenbauer, Stephan; Panse, Jens; Tucci, Alessandra; Orsucci, Lorella; Pisani, Francesco; Levis, Alessandro; Krause, Stefan W; Schmoll, Hans J; Hertenstein, Bernd; Rummel, Mathias; Smith, Jeffery; Pfreundschuh, Michael; Cabras, Giuseppina; Angrilli, Francesco; Ponzoni, Maurilio; Deckert, Martina; Politi, Letterio S; Finke, Jürgen; Reni, Michele; Cavalli, Franco; Zucca, Emanuele; Illerhaus, Gerald

2017-11-01

The International Extranodal Lymphoma Study Group-32 (IELSG32) trial is an international randomised phase 2 study that addresses two key clinical questions in the treatment of patients with newly diagnosed primary CNS lymphoma. Results of the first randomisation have demonstrated that methotrexate, cytarabine, thiotepa, and rituximab (called the MATRix regimen) is the induction combination associated with significantly better outcome compared with the other induction combinations tested. Here, we report the results of the second randomisation that addresses the efficacy of myeloablative chemotherapy supported by autologous stem-cell transplantation (ASCT), as an alternative to whole-brain radiotherapy (WBRT), as consolidation after high-dose-methotrexate-based chemoimmunotherapy. HIV-negative patients (aged 18-70 years) with newly diagnosed primary CNS lymphoma and an Eastern Cooperative Oncology Group performance status of 0-3 were randomly assigned 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 induction treatment, with adequate autologous peripheral blood stem-cell collection, and without persistent iatrogenic side-effects, were eligible for the second randomisation between WBRT (photons of 4-10 MeV; five fractions per week; fraction size 180 cGy; started within 4 weeks from the last induction course; group D) and carmustine-thiotepa conditioned ASCT (carmustine 400 mg/m 2 on day -6, and thiotepa 5 mg/kg every 12 h on days -5 and -4, followed by reinfusion of autologous peripheral blood stem cells; group E). A permuted block randomised design was adopted for both randomisations, and a computer

Topoisomerase I and II inhibitors: chemical structure, mechanisms of action and role in cancer chemotherapy

NASA Astrophysics Data System (ADS)

Dezhenkova, L. G.; Tsvetkov, V. B.; Shtil, A. A.

2014-01-01

The review summarizes and analyzes recent published data on topoisomerase I and II inhibitors as potential antitumour agents. Functions and the mechanism of action of topoisomerases are considered. The molecular mechanism of interactions between low-molecular-weight compounds and these proteins is discussed. Topoisomerase inhibitors belonging to different classes of chemical compounds are systematically covered. Assays for the inhibition of topoisomerases and the possibilities of using the computer-aided modelling for the rational design of novel drugs for cancer chemotherapy are presented. The bibliography includes 127 references.

Predictive models for customizing chemotherapy in advanced non-small cell lung cancer (NSCLC).

PubMed

Bonanno, Laura

2013-06-01

The backbone of first-line treatment for Epidermal Growth Factor (EGFR) wild-type (wt) advanced Non-small cell lung cancer (NSCLC) patients is the use of a platinum-based chemotherapy combination. The treatment is characterized by great inter-individual variability in outcome. Molecular predictive markers are extremely needed in order to identify patients most likely to benefit from platinum-based treatment and resistant ones, thus optimizing chemotherapy approach in NSCLC. Several components of DNA repair response (DRR) have been investigated as potential predictive markers. Among them, high levels of expression of ERCC1, both at protein and mRNA levels, have been associated with resistance to cisplatin in NSCLC. In addition, low levels of expression of RRM1, a target for gemcitabine, have been associated with improved OS in advanced NSCLC patients treated with cisplatin and gemcitabine. Preclinical data and retrospective analyses showed that BRCA1 is able to induce resistance to cisplatin and sensitivity to antimicrotubule agents. In addition, the mRNA levels of expression of RAP80, encoding for a protein cooperating with BRCA1 in homologous recombination (HR), have demonstrated to further sub-classify low BRCA1 NSCLC tumors, improving the predictive model. On the basis of biological knowledge on DNA repair pathway and recent controversial results from clinical validation of potential molecular markers, integrated analysis of multiple DNA repair components could improve predictive information and pave the way to a new approach to customized chemotherapy clinical trials.

The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

PubMed

Chen, Y-K; Hou, H-A; Chow, J-M; Chen, Y-C; Hsueh, P-R; Tien, H-F

2011-06-01

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

Prognostic role of lymphatic vessel density and lymphovascular invasion in chemotherapy-naive and chemotherapy-treated patients with invasive breast cancer

PubMed Central

Niemiec, Joanna A; Adamczyk, Agnieszka; Ambicka, Aleksandra; Mucha-Małecka, Anna; Wysocki, Wojciech M; Biesaga, Beata; Ziobro, Marek; Cedrych, Ida; Grela-Wojewoda, Aleksandra; Domagała-Haduch, Małgorzata; Wysocka, Joanna; Ryś, Janusz; Sas-Korczyńska, Beata

2017-01-01

It is assumed that the spread of breast cancer cells via the lymphatic system might be influenced by inflammatory reactions and/or the application of chemotherapy or molecularly targeted therapy. Therefore, we analysed survival according to lymphatic vessel density (LVD), lymphovascular invasion (LVI) (both assessed using podoplanin as immunohistochemical marker of lymphatic endothelium) and well-established clinico-pathological features in a group of 358 patients with invasive ductal breast cancer: 139 chemotherapy-naïve (pT1-2/pN0/M0) and 219 treated with chemotherapy (pT1-4/pN1-3/M0). Univariate analysis revealed that high LVD was related to unfavourable disease-free survival (DFS) in pN0/chemotherapy/trastuzumab-naïve patients (P = 0.028). Conversely, in pN+/chemotherapy-treated individuals high LVD was related to favourable DFS (P = 0.019). LVI was a significant indicator of survival (P = 0.005) only in pN0/chemotherapy/trastuzumab-naïve patients. The following parameters were significant independent adverse prognostic factors for DFS: (i) in pN0/chemotherapy/trastuzumab-naïve patients: high LVD (LVD > 7 vessels/mm2; RR = 2.7, P = 0.039), LVI (RR = 3.3, P = 0.046) and high tumor grade (G3 vs. G1 + G2; RR = 2.6, P = 0.030); (ii) in pN+/chemotherapy/trastuzumab-treated patients: low LVD (RR = 1.8, P = 0.042), the number of involved lymph nodes (pN3 vs. pN1-2; RR = 2.3, P = 0.012) and the breast cancer subtype (expression of steroid receptors together with HER2 immunonegativity and high proliferation index vs. other breast cancer immunophenotypes; RR = 3.0, P < 0.001). High LVD may identify high progression risk in pN0/chemotherapy/trastuzumab-naïve patients, and low progression risk in pN+/chemotherapy-treated patients. This phenomenon might be explained by potential involvement of lymphangiogenesis in two processes related to cancer eradication: a chemotherapy-stimulated activity of the immune system against cancer cells, or increased tumour drainage

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

Chemotherapy Use at the End of Life in Uganda

PubMed Central

Merkel, Emily C.; Menon, Manoj; Lyman, Gary H.; Ddungu, Henry; Namukwaya, Elizabeth; Leng, Mhoira; Casper, Corey

2017-01-01

Purpose Avoiding chemotherapy during the last 30 days of life has become a goal of cancer care in the United States and Europe, yet end-of-life chemotherapy administration remains a common practice worldwide. The purpose of this study was to determine the frequency of and factors predicting end-of-life chemotherapy administration in Uganda. Methods Retrospective chart review and surveys and interviews of providers were performed at the Uganda Cancer Institute (UCI), the only comprehensive cancer center in the area, which serves a catchment area of greater than 100 million people. All adult patients at the UCI with reported cancer deaths between January 1, 2014, and August 31, 2015 were included. All UCI physicians were offered a survey, and a subset of physicians were also individually interviewed. Results Three hundred ninety-two patients (65.9%) received chemotherapy. Age less than 55 years (odds ratio [OR], 2.30; P = .004), a cancer diagnosis greater than 60 days before death (OR, 9.13; P < .001), and a presenting Eastern Cooperative Oncology Group performance status of 0 to 2 (OR, 2.47; P = .001) were associated with the administration of chemotherapy. More than 45% of patients received chemotherapy in the last 30 days of life. No clinical factors were predictive of chemotherapy use in the last 30 days of life, although doctors reported using performance status, cancer stage, and tumor chemotherapy sensitivity to determine when to administer chemotherapy. Patient expectations and a lack of outcomes data were important nonclinical factors influencing chemotherapy administration. Conclusion Chemotherapy is administered to a high proportion of patients with terminal cancer in Uganda, raising concern about efficacy. Late presentation of cancer in Uganda complicates end-of-life chemotherapy recommendations, necessitating guidelines specific to sub-Saharan Africa. PMID:29244988

Multifunctional superparamagnetic iron oxide nanoparticles for combined chemotherapy and hyperthermia cancer treatment.

PubMed

Quinto, Christopher A; Mohindra, Priya; Tong, Sheng; Bao, Gang

2015-08-07

Superparamagnetic iron oxide (SPIO) nanoparticles have the potential for use as a multimodal cancer therapy agent due to their ability to carry anticancer drugs and generate localized heat when exposed to an alternating magnetic field, resulting in combined chemotherapy and hyperthermia. To explore this potential, we synthesized SPIOs with a phospholipid-polyethylene glycol (PEG) coating, and loaded Doxorubicin (DOX) with a 30.8% w/w loading capacity when the PEG length is optimized. We found that DOX-loaded SPIOs exhibited a sustained DOX release over 72 hours where the release kinetics could be altered by the PEG length. In contrast, the heating efficiency of the SPIOs showed minimal change with the PEG length. With a core size of 14 nm, the SPIOs could generate sufficient heat to raise the local temperature to 43 °C, sufficient to trigger apoptosis in cancer cells. Further, we found that DOX-loaded SPIOs resulted in cell death comparable to free DOX, and that the combined effect of DOX and SPIO-induced hyperthermia enhanced cancer cell death in vitro. This study demonstrates the potential of using phospholipid-PEG coated SPIOs for chemotherapy-hyperthermia combinatorial cancer treatment with increased efficacy.

Molecular design of sequence specific DNA alkylating agents.

PubMed

Minoshima, Masafumi; Bando, Toshikazu; Shinohara, Ken-ichi; Sugiyama, Hiroshi

2009-01-01

Sequence-specific DNA alkylating agents have great interest for novel approach to cancer chemotherapy. We designed the conjugates between pyrrole (Py)-imidazole (Im) polyamides and DNA alkylating chlorambucil moiety possessing at different positions. The sequence-specific DNA alkylation by conjugates was investigated by using high-resolution denaturing polyacrylamide gel electrophoresis (PAGE). The results showed that polyamide chlorambucil conjugates alkylate DNA at flanking adenines in recognition sequences of Py-Im polyamides, however, the reactivities and alkylation sites were influenced by the positions of conjugation. In addition, we synthesized conjugate between Py-Im polyamide and another alkylating agent, 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI). DNA alkylation reactivies by both alkylating polyamides were almost comparable. In contrast, cytotoxicities against cell lines differed greatly. These comparative studies would promote development of appropriate sequence-specific DNA alkylating polyamides against specific cancer cells.

Pharmacoeconomic evaluation of fluconazole, posaconazole and voriconazole for antifungal prophylaxis in patients with acute myeloid leukaemia undergoing first consolidation chemotherapy.

PubMed