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Cureus Dec 2023Ovarian cancer, being one of the prevalent gynecological cancers, warrants a therapy that's both effective and well tolerated. After extensive drug testing, combination... (Review)
Review
Comparison of the Efficacy of Cisplatin/Paclitaxel Versus Carboplatin/Paclitaxel in Improving Survival and Quality of Life in the Advanced Ovarian Cancer Patient Population: A Systematic Review and Meta-Analysis of Randomized Control Trials.
Ovarian cancer, being one of the prevalent gynecological cancers, warrants a therapy that's both effective and well tolerated. After extensive drug testing, combination regimens with paclitaxel plus platinum-based agents such as cisplatin/carboplatin and taxanes, have shown promising results for advanced ovarian cancer. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of two treatment regimens for advanced ovarian cancer: cisplatin/paclitaxel and carboplatin/paclitaxel. PubMed (Medline), Science Direct, and Cochrane Library were searched from inception to March 2023. The meta-analysis included patients with histologically verified International Federation of Gynaecology and Obstetrics (FIGO) stages IIB to IV ovarian carcinoma who received either carboplatin/paclitaxel or cisplatin/paclitaxel. The primary outcomes were progression-free survival (PFS), overall survival (OS), quality of life (QOL), complete response rate (CRR), and partial response rate (PRR). The revised Cochrane Risk of Bias Tool 2.0 was used to assess the quality of the RCTs The five RCTs chosen for this statistical analysis consisted of a total of 2239 participants, with 1109 receiving paclitaxel/cisplatin for treatment and the remaining 1130 receiving carboplatin/paclitaxel. Among all included outcomes, these reported significant findings: QoL (p-value=0.0002), thrombocytopenia (p=<0.00001), neurological toxicity (p-value=0.003), nausea/vomiting (p-value=<0.00001), myalgia/arthralgia (p-value=0.02), and febrile neutropenia (p-value=0.01). We concluded that the carboplatin/paclitaxel doublet endows a better quality of life (QOL) to patients along with significantly fewer gastrointestinal and neurological toxicities when compared with the cisplatin/paclitaxel combination. However, the myelosuppressive effects of carboplatin/paclitaxel remain a point of concern and may require clinical management.
PubMed: 38264391
DOI: 10.7759/cureus.51011 -
International Journal of Gynecological... Jul 2017Despite advances in cervical cancer prevention and diagnosis, outcomes for patients given a diagnosis of advanced and recurrent disease are poor. In the GOG240 trial,... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab-Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer.
OBJECTIVE
Despite advances in cervical cancer prevention and diagnosis, outcomes for patients given a diagnosis of advanced and recurrent disease are poor. In the GOG240 trial, the addition of bevacizumab to paclitaxel-topotecan or paclitaxel-cisplatin has been shown to prolong survival compared with paclitaxel-topotecan or paclitaxel-cisplatin in patients with persistent, recurrent, or metastatic disease. However, standards of care vary between regions and countries. The purpose of this systematic review and network meta-analysis was to enable a comparison between bevacizumab + chemotherapy with multiple monotherapy or combination chemotherapy regimens in the treatment for women with advanced, recurrent, or persistent cervical cancer.
METHODS/MATERIALS
A systematic literature review was conducted to identify randomized or nonrandomized controlled trials of patients with recurrent, persistent, or metastatic cervical cancer published in English from 1999 to 2015. A feasibility study was performed to assess the heterogeneity of the trials, and a network meta-analysis was conducted. Fixed- and random-effects models were fitted to calculate the hazard ratio for overall survival (OS) for all pairwise comparisons and ranking of all interventions.
RESULTS
Twenty-three studies (19 trials) met inclusion criteria and were included in the review. Sample sizes ranged from 69 to 452, and median patient age ranged from 45 to 53 years. There was a trend toward prolonged OS with cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab compared with all non-bevacizumab-containing therapies. Cisplatin-paclitaxel-bevacizumab had the highest probability of being the most efficacious compared with all regimens (68.1%), and cisplatin monotherapy had the lowest (0%).
CONCLUSIONS
The results of this network meta-analysis show that bevacizumab in combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to prolong OS over other non-bevacizumab-containing chemotherapies (eg, paclitaxel-carboplatin), which were not included in the GOG240 trial. In patients with advanced, persistent, and recurrent cervical cancer, cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in all regimens investigated in this analysis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Cisplatin; Female; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paclitaxel; Topotecan; Uterine Cervical Neoplasms
PubMed: 28448304
DOI: 10.1097/IGC.0000000000001000 -
Oncotarget Mar 2017The value of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in neoadjuvant systemic therapy for breast cancer remains uncertain. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The value of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in neoadjuvant systemic therapy for breast cancer remains uncertain.
METHODS
Both electronic databases and proceedings of oncologic meetings were included in systematic literature search. Pooled rates of pathological complete response (pCR), odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect model to determine the effect of neoadjuvant nab-paclitaxel.
RESULTS
Twenty-one studies with 2357 patients were included, 3 of which were randomized clinical trials. The aggregate pCR(ypT0/is ypN0) rate was 32% (95% CI 25-38%) in unselected breast cancer patients and variated in different subtypes. Within randomized clinical trials, the probability of achieving pCR was significantly higher in the nab-paclitaxel group than in the conventional taxanes group (OR = 1.383, 95%CI 1.141-1.676, p = 0.001). For non-hematological toxic effect, any grade and grade 3-4 peripheral sensory neuropathy occurred more frequently with nab-paclitaxel compared to paclitaxel (any grade, OR = 2.090, 95%CI 1.016-4.302, p = 0.045; grade3-4, OR = 3.766, 95%CI 2.324-6.100, p < 0.001). Hypersensitivity was more common with paclitaxel than nab-paclitaxel at any grade and grade 3-4.
CONCLUSION
nab-paclitaxel is an effective cytotoxic drug in neoadjuvant treatment of breast cancer, especially for aggressive tumors in terms of pCR. Exchange of nab-paclitaxel for conventional taxanes could significantly improve pCR rate with reasonable toxicities.
Topics: Albumin-Bound Paclitaxel; Albumins; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Fatigue; Female; Humans; Leukopenia; Nanoparticles; Nausea; Neoadjuvant Therapy; Neutropenia; Paclitaxel; Treatment Outcome
PubMed: 28061451
DOI: 10.18632/oncotarget.14477 -
Frontiers in Veterinary Science 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a common consequence of cancer treatment and pain is a frequent complaint of the patients. Paclitaxel, a cytostatic...
INTRODUCTION
Chemotherapy-induced peripheral neuropathy (CIPN) is a common consequence of cancer treatment and pain is a frequent complaint of the patients. Paclitaxel, a cytostatic drug, generates a well-described peripheral nerve injury and neuroinflammation, which may be experimentally mimicked in animal models. We conducted a systematic review analyzing the experimental design, reporting and mechanisms underlying paclitaxel-induced neuropathy in the included studies to establish the perspectives of translation of the current literature in models of CIPN.
METHODS
We elected studies published in Pubmed and Scopus between 1 January 2018 and 3 December 2022.
RESULTS
According to a defined mesh of keywords searched, and after applying exclusion and inclusion criteria, 70 original studies were included and analyzed in detail. Most studies used male Sprague-Dawley rats to induce paclitaxel-induced neuropathy, used low doses of paclitaxel, and the analyzed studies mainly focused at 14-28 days of CIPN. Mechanical nociceptive tests were preferred in the behavioral evaluation. The mechanisms under study were mainly neuroinflammation of peripheral nerves. The overall methodological quality was considered moderate, and the risk of bias was unclear.
DISCUSSION
Despite the ample preclinical research in paclitaxel-induced neuropathy, this systematic review alerts to some flaws in the experimental design along with limitations in reporting, e.g., lack of representation of both sexes in experimental work and the lack of reporting of the ARRIVE guidelines. This may limit the reproducibility of preclinical studies in CIPN. In addition, the clinical features of CIPN should be considered when designing animal experiments, such as sex and age of the CIPN patients. In this way the experimental studies aiming to establish the mechanisms of CIPN may allow the development of new drugs to treat CIPN and translation in the research of CIPN could be improved.
PubMed: 38188718
DOI: 10.3389/fvets.2023.1264668 -
Cancers Apr 2019Gemcitabine and nab-paclitaxel (GEM-NAB) and the combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) are valid first-line options for advanced or... (Review)
Review
Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis.
Gemcitabine and nab-paclitaxel (GEM-NAB) and the combination of 5-fluorouracil, oxaliplatin, and irinotecan (FOLFIRINOX) are valid first-line options for advanced or metastatic pancreatic cancer (mPC). However, no randomized trials comparing the two schemes have been performed. This meta-analysis aims to compare GEM-NAB and FOLFIRINOX in terms of safety and effectiveness, taking into account data from real-life studies on mPC. We systematically searched PubMed, EMBASE and Cochrane library up to November 2018 to identify retrospective or cohort studies on mPC comparing GEM-NAB and FOLFIRINOX. We included 16 retrospective studies, including 3813 patients (2123 treated with GEM-NAB and 1690 treated with FOLFIRINOX). Despite a median weighted overall survival (OS) difference in favor of FOLFIRINOX (mean difference: 1.15, 95% confidence interval CI 0.08⁻2.22, = 0.03), in whole population OS was similar (hazard ratio (HR = 0.99, 95% CI 0.84⁻1.16; = 0.9). PFS was also not different between the two arms (HR = 0.88, 95% CI 0.71⁻1.1; = 0.26). The overall response rate was similar (25 vs. 24% with GEM-NAB and FOLFIRINOX). Among grade 3⁻4 toxicities, neutropenia, febrile neutropenia, and nausea were lower with GEM-NAB, while neurotoxicity and anemia were lower with FOLFIRINOX. In conclusion, despite a numerically longer median OS with FOLFIRINOX as compared to GEM-NAB, the overall risk of death and progression were similar. Their toxicity was different with less nausea, neutropenia, and febrile neutropenia with GEM-NAB, as compared to less neurotoxicity and anemia with FOLFIRINOX. Therefore, analysis of non-randomized "real world" studies to date has not provided evidence of a major benefit of one regimen over the other.
PubMed: 30959763
DOI: 10.3390/cancers11040484 -
Chinese Medicine 2020Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to... (Review)
Review
BACKGROUND
Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to identify potential pharmacokinetic or pharmacodynamic interactions from the existing literature to ensure their effective and safe combination usage in cancer patients.
METHODS
A systematic search was conducted on nine major Chinese and English databases, including China Journal Net, Allied and Complementary Medicine Database, and Ovid MEDLINE, etc., to identify clinical, animal, and in-vitro studies that evaluate the effect of combined use of Lingzhi or Yunzhi with cytotoxic drugs. The Jadad scale was used to assess the quality of clinical studies.
RESULTS
This search identified 213 studies, including 77 clinical studies that reported on the combined use of cytotoxic drugs with Yunzhi (n = 56) or Lingzhi (n = 21). Majority of these clinical studies demonstrated modest methodological quality. In clinical practice, the most commonly used cytotoxic drugs with Lingzhi were cisplatin, 5-fluorouracil (5-FU) and paclitaxel, whereas Tegafur/uracil (UFT)/Tegafur, 5-FU, and mitomycin were the ones used more often with Yunzhi. Only two clinical pharmacokinetic studies were available showing no significant interactions between Polysaccharide K (PSK) and Tegafur. From the pharmacodynamic interactions perspective, combination uses of Yunzhi/Lingzhi with cytotoxic drugs in clinical practice could lead to improvement in survival (n = 31) and quality of life (n = 17), reduction in tumor lesions (n = 22), immune modulation (n = 38), and alleviation of chemotherapy-related side effects (n = 14) with no reported adverse effects.
CONCLUSION
Our findings suggest that the clinical combination use of Lingzhi or Yunzhi with cytotoxic drugs could enhance the efficacy and ameliorate the adverse effects of cytotoxic drugs, leading to improved quality of life in cancer patients. More high quality clinical studies including pharmacokinetic herb-drug interactions studies are warranted to verify these observations and mechanisms involved. Based on the high quality clinical data, pharmacoepidemiology methods and bioinformatics or data mining could be adopt for further identification of clinical meaningful herb-drug interactions in cancer therapies.
PubMed: 32724333
DOI: 10.1186/s13020-020-00356-4 -
The Cochrane Database of Systematic... Jan 2016Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will... (Review)
Review
BACKGROUND
Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.
OBJECTIVES
To determine which chemotherapy regimen/s for the treatment of resistant or relapsed GTN is/are the most effective and the least toxic.
SEARCH METHODS
We searched the Cochrane Gynaecological Cancer Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4), MEDLINE and EMBASE up to October 2011. In addition, we handsearched the relevant society conference proceedings and study reference lists. For the updated review, we searched Cochrane Group Specialised Register, CENTRAL, MEDLINE and EMBASE to 16 Novemeber 2015. In addition, we searched online clinical trial registries for ongoing trials.
SELECTION CRITERIA
Only randomised controlled trials (RCTs) were included.
DATA COLLECTION AND ANALYSIS
We designed a data extraction form and planned to use random-effects methods in Review Manager 5.1 for meta-analyses.
MAIN RESULTS
The search identified no RCTs; therefore we were unable to perform any meta-analyses.
AUTHORS' CONCLUSIONS
RCTs in GTN are scarce owing to the low prevalence of this disease and its highly chemosensitive nature. As chemotherapeutic agents may be associated with substantial side effects, the ideal treatment should achieve maximum efficacy with minimal side effects. For methotrexate-resistant or recurrent low-risk GTN, a common practice is to use sequential five-day dactinomycin, followed by MAC (methotrexate, dactinomycin, cyclophosphamide) or EMA/CO (etoposide, methotrexate, dactinomycin, cyclophosphamide, vinblastine) if further salvage therapy is required. However, five-day dactinomycin is associated with more side effects than pulsed dactinomycin, therefore an RCT comparing the relative efficacy and safety of these two regimens in the context of failed primary methotrexate treatment is desirable.For high-risk GTN, EMA/CO is the most commonly used first-line therapy, with platinum-etoposide combinations, particularly EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin), being favoured as salvage therapy. Alternatives, including TP/TE (paclitaxel, cisplatin/ paclitaxel, etoposide), BEP (bleomycin, etoposide, cisplatin), FAEV (floxuridine, dactinomycin, etoposide, vincristine) and FA (5-fluorouracil (5-FU), dactinomycin), may be as effective as EMA/EP and associated with fewer side effects; however, this is not clear from the available evidence and needs testing in well-designed RCTs. In the UK, an RCT comparing interventions for resistant/recurrent GTN will be very challenging owing to the small numbers of patients with this scenario. International multicentre collaboration is therefore needed to provide the high-quality evidence required to determine which salvage regimen/s have the best effectiveness-to-toxicity ratio in low- and high-risk disease. Future research should include economic evaluations and long-term surveillance for secondary neoplasms.
Topics: Drug Resistance, Neoplasm; Female; Gestational Trophoblastic Disease; Humans; Neoplasm Recurrence, Local; Pregnancy
PubMed: 26760424
DOI: 10.1002/14651858.CD008891.pub3 -
Frontiers in Pharmacology 2023In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have...
In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart's function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity. This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients' treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760.
PubMed: 37383708
DOI: 10.3389/fphar.2023.1137983 -
Oncotarget Dec 2016The current gold-standard for the first-line treatment in IIIb/IV stages of epithelial ovarian cancer (EOC) is the combination of carboplatin and paclitaxel plus... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The current gold-standard for the first-line treatment in IIIb/IV stages of epithelial ovarian cancer (EOC) is the combination of carboplatin and paclitaxel plus bevacizumab in some countries. In the era of personalized medicine, there is still uncertainty on the impact of several molecularly targeted agents, which have been investigated for the management of this disease. To shed light on the actual role of targeted therapy in EOC, a systematic review and meta-analysis was performed.
METHODS
Clinical trials were selected by searching "Pubmed" database and abstracts from major cancer meetings within the time-frame of January 2004-June 2015. The endpoints were survival outcome and response rate (RR). Hazard ratios (HRs) of survival outcomes, with confidence intervals and odds-ratios (ORs) of RR, were extracted from retrieved studies and used for current analysis. Meta-analysis was carried out by random effect model.
RESULTS
30 randomized trials for a total of 10,530 patients were selected and included in the final analysis. A benefit in terms of OS (pooled HR 0.915; 95%CI 0.840-0.997; p=0.043), particularly for anti-angiogenetic agents (HR 0.872; 95%CI 0.761-1.000; p=0.049), has been demonstrated for targeted therapy. Moreover, a significant advantage in platinum-resistant subgroup in term of PFS (HR 0.755; 95%CI 0.624-0.912; p=0.004) was found.
CONCLUSIONS
This systematic review and meta-analysis provide the first evidence that targeted therapy is potentially able to translate into improved survival of EOC patients, with a major role played by anti-angiogenetic drugs. The role of target therapy is underlined in the platinum-resistant setting that represents the "pain in the neck" in EOC management.
Topics: Angiogenesis Inhibitors; Biomarkers, Tumor; Disease Progression; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Humans; Molecular Targeted Therapy; Odds Ratio; Ovarian Neoplasms; Patient Selection; Precision Medicine; Risk Factors; Signal Transduction; Time Factors; Treatment Outcome
PubMed: 27764790
DOI: 10.18632/oncotarget.12633 -
Frontiers in Medicine 2023This meta-analysis was exerted in assessing the anticancer efficacy and safety of nab-paclitaxel (nab-P) when combined with platinum compound agents for therapy in...
PURPOSE
This meta-analysis was exerted in assessing the anticancer efficacy and safety of nab-paclitaxel (nab-P) when combined with platinum compound agents for therapy in patients with non-small cell lung cancer (NSCLC).
METHOD
We systematically searched the following seven electronic databases: PubMed, Cochrane Library, Web of Science, Embase, CNKI, Wan Fang, and China Science and Technology Journal Data. Randomized comparative clinical [randomized controlled clinical trial (RCT)] studies on nab-P plus platinum and carboplatin or cisplatin in combination with conventional chemotherapy agents or traditional paclitaxel were searched.
RESULTS
A total of 19 RCT studies involving 6,011 patients were analyzed. The primary outcome includes the overall response rate (ORR), overall survival (OS), and progression-free survival (PFS). The secondary outcome includes adverse events (AEs). Nab-P combined with platinum (carboplatin/cisplatin) had a better ORR [odds ratio (OR) = 1.66, 95% confidence interval (CI) (1.34, 2.05), < 0.001] and improved PFS [hazard ratio (HR) = 0.84, 95% CI: (0.74, 0.94), = 0.01] and OS [HR = 0.86, 95% CI: (0.78, 0.96), = 0.008] in NSCLC patients. ORR [OR = 2.18, 95% CI: (1.07, 4.43)], PFS [HR = 0.62, 95% CI: (0.40, 0.97)], and OS [HR = 0.63, 95% CI: (0.49, 0.81)] were significantly improved among patients aged >70 years, and ORR [OR = 1.80, 95% CI: (1.20, 2.70)] and PFS [HR = 0.74, 95% CI: (0.56, 0.97)] were significantly elevated with SCC rate ≥65% in NSCLC patients (all > 0.05). Among the adverse effects, the prevalence of neutropenia, neuralgia, and arthralgia/myalgia (≥ grade 3) compared to that of the control group. On the other hand, the prevalence of anemia and thrombocytopenia was higher in the nab-P plus platinum (carboplatin/cisplatin) compared to that of controls. It is worth noting that fatigue did not show statistical significance.
CONCLUSION
Nab-P in combination with carboplatin/cisplatin regimen improves efficacy and tolerability in patients with NSCLC.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022288499.
PubMed: 37554498
DOI: 10.3389/fmed.2023.1139248