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British Journal of Haematology Jul 2019The question of which chemotherapy induction provides the best results for indolent lymphoma patients is yet unanswered. Different regimens have been compared, none of... (Comparative Study)
Comparative Study Meta-Analysis
The question of which chemotherapy induction provides the best results for indolent lymphoma patients is yet unanswered. Different regimens have been compared, none of which has been shown to improve overall survival. The use of bendamustine is growing. A number of trials evaluated its efficacy for patients with indolent B-cell lymphoid neoplasms, including chronic lymphocytic leukaemia (CLL). To evaluate the efficacy of bendamustine in that population we performed a systematic review and meta-analysis of 9 randomised controlled trials (2726 patients). Bendamustine was compared to fludarabine-containing regimens, CVP (cyclophosphamide, vincristine, prednisolone), CHOP (CVP+ doxorubicin) and chlorambucil. Due to insufficient reported data, six of the nine trials were included in analysis of overall survival. Bendamustine was associated with a prolonged overall survival, (hazard ratio 0·79, 95% confidence interval 0·65-0·95). Data regarding quality of life was reported for two trials, therefore too scarce to pool. The risk of neutropenia was reduced with bendamustine treatment compared to other chemotherapy. Bendamustine induction is an efficacious option for patients with indolent lymphoma, and CLL. Maintenance therapy was not evaluated after bendamustine induction, and potentially there is an interaction between the two. Chemotherapy-free approach was shown to be efficacious for patients with CLL, while toxicity with that approach is not negligible.
Topics: Antineoplastic Combined Chemotherapy Protocols; B-Lymphocytes; Bendamustine Hydrochloride; Chlorambucil; Cyclophosphamide; Disease-Free Survival; Doxorubicin; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell; Maintenance Chemotherapy; Prednisone; Randomized Controlled Trials as Topic; Survival Rate; Vincristine
PubMed: 30980398
DOI: 10.1111/bjh.15901 -
Scientific Reports Mar 2021Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients... (Meta-Analysis)
Meta-Analysis
Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Trained DOX-treated animals improved 7.40% (95% CI 5.75-9.05, p < 0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior effect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27-10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior effect size in FS (MD = 7.89, 95% CI 6.11-9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.
Topics: Animals; Cardiomyopathies; Cardiotoxicity; Doxorubicin; Echocardiography; Exercise; Female; Heart; Humans; Male; Neoplasms; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley
PubMed: 33737561
DOI: 10.1038/s41598-021-83877-8 -
Reproductive Toxicology (Elmsford, N.Y.) Apr 2020Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold...
A closed vitrification system enables a murine ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting activity of microcystins.
Increasing evidence reveals that a broad spectrum of environmental chemicals and pharmaceutical compounds cause female ovarian toxicity (ovotoxicity). The current gold standard of ovotoxicity testing largely relies on whole laboratory animals, but in vivo models are time consuming, costly, and present animal welfare concerns. We previously demonstrated that the 3D encapsulated in vitro follicle growth (eIVFG) is a robust in vitro model for ovotoxicity testing. However, the follicle preparation process is complex and highly dependent on technical skills. Here, we aimed to use vitrification method to cryopreserve murine immature follicles for a high-content eIVFG, chemical exposure, and ovotoxicity screening. Results indicated that a closed vitrification system combined with optimized vitrification protocols preserved mouse follicle viability and functionality and vitrified follicles exhibited comparable follicle and oocyte reproductive outcomes to freshly harvested follicles during eIVFG, including follicle survival and development, ovarian steroidogenesis, and oocyte maturation and ovulation. Moreover, vitrified follicles consistently responded to ovotoxic chemical, doxorubicin (DOX). We further used vitrified follicles to test the response of microcystins (MCs), an emerging category of environmental contaminants produced by cyanobacteria associated with harmful algal blooms (HABs), and found that different congeners of MCs exhibited differential ovotoxicities. In summary, our study demonstrates that vitrification enables a long-term-storage and ready-to-use ovarian follicle bank for high-throughput ovotoxicity screening, which identifies endocrine disrupting effects of MCs.
Topics: Animals; Antibiotics, Antineoplastic; Cryopreservation; Doxorubicin; Endocrine Disruptors; Female; High-Throughput Screening Assays; Mice; Microcystins; Ovarian Follicle; Vitrification
PubMed: 32017985
DOI: 10.1016/j.reprotox.2020.01.009 -
Medicine Apr 2021Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a...
BACKGROUND
Uterine leiomyosarcomas are rare malignant mesenchymal tumors. The systemic treatment of these tumors includes chemotherapy and radiotherapy. However, there are still a lot of unanswered questions regarding the ideal therapeutic approach.
METHODS
We have conducted a systematic review of the treatment strategies of uterine leiomyosarcomas for the last ten years.
RESULTS
Adjuvant chemotherapy is still a matter of dilemma. Doxorubicin based chemotherapy or the combination of Gemcitabine-Docetaxel are the regimens of choice for the first line setting. Beyond the first line, there are several options;, including chemotherapy, targeted therapy, and recently efforts of introducing immunotherapy to the therapeutic armamentarium of clinicians treating uterine leiomyosarcomas.
CONCLUSIONS
Despite the efforts of the clinicians dealing with uterine leiomyosarcomas, the optimal therapeutic algorithm is yet to be described.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Deoxycytidine; Doxorubicin; Female; Humans; Immunotherapy; Leiomyosarcoma; Molecular Targeted Therapy; Treatment Outcome; Uterine Neoplasms; Gemcitabine
PubMed: 33787622
DOI: 10.1097/MD.0000000000025309 -
Oncogene Jan 2023Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate,...
Over the last 40 years osteosarcoma (OS) survival has stagnated with patients commonly resistant to neoadjuvant MAP chemotherapy involving high dose methotrexate, adriamycin (doxorubicin) and platinum (cisplatin). Due to the rarity of OS, the generation of relevant cell models as tools for drug discovery is paramount to tackling this issue. Four literature databases were systematically searched using pre-determined search terms to identify MAP resistant OS cell lines and patients. Drug exposure strategies used to develop cell models of resistance and the impact of these on the differential expression of resistance associated genes, proteins and non-coding RNAs are reported. A comparison to clinical studies in relation to chemotherapy response, relapse and metastasis was then made. The search retrieved 1891 papers of which 52 were relevant. Commonly, cell lines were derived from Caucasian patients with epithelial or fibroblastic subtypes. The strategy for model development varied with most opting for continuous over pulsed chemotherapy exposure. A diverse resistance level was observed between models (2.2-338 fold) with 63% of models exceeding clinically reported resistance levels which may affect the expression of chemoresistance factors. In vitro p-glycoprotein overexpression is a key resistance mechanism; however, from the available literature to date this does not translate to innate resistance in patients. The selection of models with a lower fold resistance may better reflect the clinical situation. A comparison of standardised strategies in models and variants should be performed to determine their impact on resistance markers. Clinical studies are required to determine the impact of resistance markers identified in vitro in poor responders to MAP treatment, specifically with respect to innate and acquired resistance. A shift from seeking disputed and undruggable mechanisms to clinically relevant resistance mechanisms may identify key resistance markers that can be targeted for patient benefit after a 40-year wait.
Topics: Humans; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Clinical Relevance; Doxorubicin; Neoplasm Recurrence, Local; Osteosarcoma; Drug Resistance, Neoplasm
PubMed: 36434179
DOI: 10.1038/s41388-022-02529-x -
Journal of Global Oncology Sep 2018Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile... (Meta-Analysis)
Meta-Analysis
PURPOSE
Despite widespread use of fluorouracil, epirubicin, cyclophosphamide, docetaxel (FEC-D) chemotherapy in breast cancer, the optimal strategy for primary febrile neutropenia (FN) prophylaxis remains unknown. A systematic review was therefore performed.
METHODS
Embase, Ovid MEDLINE, PubMed, Cochrane Database of Systematic Reviews, Cochrane Register of Controlled Trials, and conference proceedings were searched from 1946 to April 2016 for trials that reported the effectiveness of primary FN prophylaxis with FEC-D chemotherapy. Outcome measures were incidence of FN; treatment-related hospitalizations; chemotherapy dose delays, reductions, and discontinuations; and adverse events from prophylaxis.
RESULTS
Of 2,205 identified citations, eight studies (n = 1,250) met our eligibility criteria. Three additional studies (n = 293) were identified from a prior systematic review. Three randomized controlled trials (n = 576), one phase IV single-arm trial (n = 69), one prospective observational study (n = 37), and six retrospective studies (n = 861) were identified. Agents investigated were pegfilgrastim (n = 108), filgrastim (n = 1,119), and ciprofloxacin (n = 89). The heterogeneity of studies meant that a narrative synthesis of results was performed. Median FN rates for patients who received FEC-D with and without primary prophylaxis were 10.1% (interquartile range [IQR], 3.9% to 22.6%) and 23.9% (IQR, 9.2% to 27.3%), respectively. In the absence of primary prophylaxis, FN was more common during docetaxel than during FEC. Data from six studies showed a median rate of dose reductions and delays of 6.1% (IQR, 3.1% to 14.3%) and 19.3% (IQR, 10.5% to 32.8%), respectively, that occurred as a consequence of FN. Toxicity from prophylaxis itself was rarely reported.
CONCLUSION
Primary FN prophylaxis is effective in patients who receive FEC-D chemotherapy. The paucity of prospective data makes optimal recommendations about the choice and timing of prophylaxis challenging.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemoprevention; Cyclophosphamide; Docetaxel; Epirubicin; Febrile Neutropenia; Female; Fluorouracil; Humans; Risk Factors; Treatment Outcome
PubMed: 30241156
DOI: 10.1200/JGO.2016.008540 -
Haematologica Jul 2020Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing...
Efficacy of central nervous system prophylaxis with stand-alone intrathecal chemotherapy in diffuse large B-cell lymphoma patients treated with anthracycline-based chemotherapy in the rituximab era: a systematic review.
Central nervous system (CNS) relapse of diffuse large B-cell lymphoma remains uncommon but catastrophic. The benefit of standalone intrathecal prophylaxis in reducing CNS recurrence is unclear and remains controversial. No systematic review analysing the evidence for stand-alone intrathecal prophylaxis has been performed in the era of anti-CD20 monoclonal antibody therapy. A comprehensive search (01/2002-01/2019) was systematically performed using Ovid MEDLINE, Ovid EMBASE and Cochrane. Studies were selected from a total of 804, screened based on predefined inclusion/exclusion criteria, and were critically appraised. Three post hoc analyses (RICOVER-60, RCHOP-14/21, GOYA), one prospective database and 10 retrospective series were included. 7,357 rituximab/obinutuzumab-exposed patients were analysed. The median percentage receiving intrathecal prophylaxis was 11.9%. Cumulative CNS relapse incidence ranged from 1.9% at 6.5 years to 8.4% at 5 years. Median time (of medians) to CNS relapse was 10 months. 73% developed isolated CNS relapses, 24% concurrent CNS/systemic relapse, and 3% post-systemic relapse. Reported CNS relapse sites were: parenchymal (58%), leptomeningeal (27%), and both (12%). Event rates were low resulting in limited power within each study to provide robust univariable/multivariable analysis. Intrathecal prophylaxis was not a univariable or multivariable factor associated with a reduction in CNS relapse in any study. We found no strong evidence for the benefit, or indeed genuine lack of benefit, of stand-alone intrathecal prophylaxis in preventing CNS relapse in diffuse large B-cell lymphoma-treated patients using anthracycline-based immunochemotherapy. Current published study designs limit the strength of such conclusions.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System; Central Nervous System Neoplasms; Cyclophosphamide; Doxorubicin; Humans; Lymphoma, Large B-Cell, Diffuse; Neoplasm Recurrence, Local; Prednisone; Retrospective Studies; Rituximab; Vincristine
PubMed: 31488560
DOI: 10.3324/haematol.2019.229948 -
International Journal of... 2006Kaposi's sarcoma (KS) is a form of skin cancer that can involve internal organs. It is often found in patients with acquired immunodeficiency syndrome (AIDS) and can be... (Review)
Review
Kaposi's sarcoma (KS) is a form of skin cancer that can involve internal organs. It is often found in patients with acquired immunodeficiency syndrome (AIDS) and can be fatal. Kaposi's sarcoma produces pink, purple or brown tumors on the skin, mucous membranes or internal organs. Treatment goals for KS are simple: to reduce the severity of the symptoms, shrink tumors and prevent disease progression. Unfortunately, there is no single best treatment-plan that can achieve all these goals. With widespread KS lesions over the body surface or evidence of spreading to other parts of the body, the physicians need to treat the patients with systemic chemotherapy. A new class of drugs, called liposomal anthracyclines, appears to produce good results with fewer toxic side effects than more conventional cytotoxic drugs. One of these drugs, pegylated liposomal doxorubicin (PLD) has become the treatment of choice. This article summarizes all the studies with PLD in systemic Kaposi's sarcoma.
Topics: Anthracyclines; Clinical Trials as Topic; Doxorubicin; Humans; Polyethylene Glycols; Sarcoma, Kaposi
PubMed: 16831292
DOI: 10.1177/039463200601900202 -
British Journal of Cancer Nov 2005Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate... (Meta-Analysis)
Meta-Analysis
Surrogate markers may help predict the effects of first-line treatment on survival. This metaregression analysis examines the relationship between several surrogate markers and survival in women with advanced breast cancer after receiving first-line combination anthracycline chemotherapy 5-fluorouracil, adriamycin and cyclophosphamide (FAC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC). From a systematic literature review, we identified 42 randomised trials. The surrogate markers were complete or partial tumour response, progressive disease and time to progression. The treatment effect on survival was quantified by the hazard ratio. The treatment effect on each surrogate marker was quantified by the odds ratio (or ratio of median time to progression). The relationship between survival and each surrogate marker was assessed by a weighted linear regression of the hazard ratio against the odds ratio. There was a significant linear association between survival and complete or partial tumour response (P<0.001, R(2)=34%), complete tumour response (P=0.02, R(2)=12%), progressive disease (P<0.001, R(2)=38%) and time to progression (P<0.0001, R(2)=56%); R(2) is the proportion of the variability in the treatment effect on survival that is explained by the treatment effect on the surrogate marker. Time to progression may be a useful surrogate marker for predicting survival in women receiving first-line anthracycline chemotherapy and could be used to estimate the survival benefit in future trials of first-line chemotherapy compared to FAC or FEC. The other markers, tumour response and progressive disease, were less good.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Cyclophosphamide; Disease Progression; Doxorubicin; Epirubicin; Female; Fluorouracil; Humans; Randomized Controlled Trials as Topic; Regression Analysis; Survival Analysis
PubMed: 16278665
DOI: 10.1038/sj.bjc.6602858 -
The Oncologist 2010To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of... (Comparative Study)
Comparative Study
Tolerability, efficacy, and safety of pegylated liposomal Doxorubicin in combination with Carboplatin versus gemcitabine-Carboplatin for the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review.
OBJECTIVE
To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine-carboplatin (Gem-Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature.
METHODS
Using the PubMed database, a systematic review of peer-reviewed literature published between January 2000 and September 2009 was undertaken to identify studies related to the treatment of patients with PSROC with PLD-Carbo or Gem-Carbo. Studies reporting either response rate, progression-free survival (PFS), and/or overall survival (OS) were included. Treatment regimens, efficacy endpoints, and safety profiles were compared between the two combination therapies.
RESULTS
Ten studies evaluating 608 patients (PLD-Carbo: 5 studies, 278 patients; Gem-Carbo: 5 studies, 330 patients) were identified. The mean planned doses were: PLD, 34.8 mg/m(2) and Gem, 993 mg/m(2). The dose intensity reported in Gem trials was lower (75% of the planned dose) than the dose intensity reported in PLD trials (93.7% of the planned dose), suggesting better tolerability for the PLD-Carbo regimen. Among patients receiving PLD-Carbo, 60.2% achieved a response (complete, 27.0%; partial, 33.2%), versus 51.4% of patients treated with Gem-Carbo (complete, 19.2%; partial, 32.2%). The median PFS times were 10.6 months and 8.9 months in the PLD-Carbo and the Gem-Carbo populations, respectively. The median OS was longer for the PLD-Carbo regimen (27.1 months) than for the Gem-Carbo regimen (19.7 months). The hematological safety profiles were comparable in the two groups, although grade III or IV anemia (PLD-Carbo, 13.6%; Gem-Carbo, 24.5%) and neutropenia (PLD-Carbo, 45.5%; Gem-Carbo, 62.9%) were more common in patients receiving Gem-Carbo.
CONCLUSION
Results from this systematic analysis of peer-reviewed literature suggest that PLD-Carbo therapy is a rational alternative to Gem-Carbo for the treatment of patients with PSROC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Deoxycytidine; Disease-Free Survival; Doxorubicin; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Polyethylene Glycols; Gemcitabine
PubMed: 20930103
DOI: 10.1634/theoncologist.2009-0331