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Frontiers in Oncology 2021Paclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of...
BACKGROUND
Paclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of pharmacological and non-pharmacological neuroprotective interventions in preventing PIPN incidence.
METHODS
Biomedical literature databases were searched from years 2000 to 2021 for trials comparing neuroprotective interventions and control. Meta-analysis was performed using the random-effects model. The primary outcome was the incidence of PIPN.
RESULTS
Of 24 relevant controlled trials, 14 were eligible for meta-analysis. Pooled results from seven non-pharmacological trials were associated with a statistically significant 48% relative reduction of PIPN risk with low heterogeneity. Conversely, pooled results from six pharmacological trials were associated with a significant 20% relative reduction of PIPN risk with moderate heterogeneity. Both pharmacological and non-pharmacological approaches appear effective in reducing PIPN incidence in the treatment arm compared to control (pooled RR < 1).
CONCLUSION
Current evidence suggests that both interventions may reduce PIPN risk. Non-pharmacological interventions appear more effective than pharmacological interventions.
PubMed: 35070969
DOI: 10.3389/fonc.2021.763229 -
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 -
World Journal of Oncology Oct 2023The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established.... (Review)
Review
BACKGROUND
The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established. We conducted an analysis of retrospective studies to assess the efficacy and safety of these two regimens by comparing their survival and safety outcomes in patients with PC.
METHODS
We conducted an extensive review of two electronic databases from inception till February 2023 to include all the relevant studies that compared FFX with GnP published and unpublished work. Retrospective studies were only included. Overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs), while objective response rate (ORR) and safety outcomes were pooled using odds ratios (ORs) with 95% confidence interval (CI) using the random effects model.
RESULTS
A total of 7,030 patients were identified in a total of 21 articles that were shortlisted. Pooled results concluded that neither FFX nor GnP was associated to increase the OS time (HR: 0.93, 95% CI: 0.83 - 1.04; P = 0.0001); however, FFX was more likely associated with increased PFS when compared to GnP (HR: 0.88, 95% CI: 0.81 - 0.97; P < 0.0001). ORR proved to be non-significant between the two regimens (OR: 0.90, 95% CI: 0.64 - 1.27; P = 0.15). Safety outcomes included neutropenia, anemia, thrombocytopenia and diarrhea. GnP was more associated with diarrhea (OR: 1.96, 95% CI: 1.22 - 3.15; P = 0.001), while FFX was seen to cause anemia (OR: 0.70, 95% CI: 0.51 - 0.98; P = 0.10) in PC patients. Neutropenia and thrombocytopenia were in-significant in the two drug regimens (OR: 1.10, 95% CI: 0.92 - 1.31; P = 0.33 and OR: 0.83, 95% CI: 0.60 - 1.13; P = 0.23, respectively).
CONCLUSION
FFX and GnP showed a significant difference in increasing the PFS, while no difference was observed while measuring OS. Safety outcomes showed that FFX and GnP shared similar safety profiles as FFX was associated with hematological outcomes, while GnP was more associated with non-hematological outcomes.
PubMed: 37869244
DOI: 10.14740/wjon1604 -
Gynecologic Oncology Apr 2014The prognosis of advanced/recurrent cervical cancer patients is generally poor with 1-year survival ranging between 15 and 20%. Cisplatin (CDDP) based treatments are... (Review)
Review
INTRODUCTION
The prognosis of advanced/recurrent cervical cancer patients is generally poor with 1-year survival ranging between 15 and 20%. Cisplatin (CDDP) based treatments are considered the most effective regimens; unfortunately toxicity is an issue in a population in which the treatment remains palliative in the finality. Carboplatin (CBDCA), with its more favorable non toxicity profile and the convenience of outpatient administration, may be a suitable alternative to CDDP in combination regimens.
MATERIALS AND METHODS
We performed a systematic review of the literature comparing CDDP and CBDCA based chemotherapy for advanced cervical cancer (recurrent, persistent or metastatic disease). Only studies that met the following criteria were considered for the present review: 1) patients treated with CDDP/paclitaxel or CBDCA/paclitaxel combinations as first line chemotherapy for metastatic disease; 2) one or more of the following data available: overall response rate (RR), progression free survival (PFS) or time to progression (TTP), overall survival (OS); 3) single-arm retrospective or prospective study; and 4) at least 20 patients enrolled.
RESULTS
17 eligible studies comprehensive of 1181 patients were included in the final analysis. The objective RR was 48.5% for CBDCA and 49.3% for CDDP-based chemotherapy. Median PFS for CDDP and CBDCA-based treatments was 6.9months and 5months respectively (p=0.03); the corresponding figures for median OS were 12.87 and 10months respectively (p=0.17).
DISCUSSION
Our study indicates that CBDCA may represent an attractive and valid alternative to the more toxic and equally effective CDDP in the treatment of advanced or recurrent cervical cancer.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Cisplatin; Disease-Free Survival; Female; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Paclitaxel; Treatment Outcome; Uterine Cervical Neoplasms
PubMed: 24486604
DOI: 10.1016/j.ygyno.2014.01.042 -
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 -
Current Medical Research and Opinion Feb 2013Docetaxel and paclitaxel show significant clinical activity in metastatic breast cancer (MBC) and have been approved for MBC by the U.S. Food and Drug Administration,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Docetaxel and paclitaxel show significant clinical activity in metastatic breast cancer (MBC) and have been approved for MBC by the U.S. Food and Drug Administration, but it is still unclear whether a paclitaxel-based regimen improves outcomes over a docetaxel-based regimen in patients with MBC. We therefore performed a meta-analysis of randomized controlled trials to compare the safety and efficacy of these two regimens in MBC.
METHODS
We systematically searched for randomized controlled trials that comparing paclitaxel-based with docetaxel-based regimens in patients with MBC in PubMed (up to January 2012), Embase (1980 to January 2012), and the Cochrane databases (up to January 2012). Abstracts presented at conferences (up to January 2011) were also searched. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by Stata version 12.0 software (Stata Corporation, College Station, TX, USA).
RESULTS
Seven eligible trials involving 1694 patients with MBC were selected. Our results showed that a paclitaxel-based regimen was comparable to a docetaxel-based regimen for MBC patients in terms of OS (HR: 0.87, 95% CI: 0.60-1.27, p = 0.48), PFS (HR: 0.76, 95% CI: 0.58-1.00, p = 0.052), TTP (HR: 1.13, 95% CI: 0.81-1.58, p = 0.46), and ORR (RR: 1.01, 95% CI: 0.88-1.15, p = 0.92), but fewer grade 3 or 4 adverse events including anemia (RR: 0.64, 95% CI: 0.44-0.94, p = 0.023), neutropenia (RR: 0.74, 95% CI: 0.58-0.93, p = 0.011), febrile neutropenia (RR: 0.38, 95% CI: 0.15-0.96, p = 0.041), thrombopenia (RR: 0.62, 95% CI: 0.41-0.96, p = 0.033), mucositis (RR: 0.082, 95% CI: 0.025-0.27, p < 0.001), diarrhea (RR: 0.19, 95% CI: 0.081-0.47, p < 0.001) and fatigue (RR: 0.43, 95% CI: 0.20-0.96, p = 0.039) were observed in the paclitaxel-based regimen. However, limitations of our study needed to be considered when interpreting these results: our study was a meta-analysis of published data, and there was significant heterogeneity among included trials. Potential publication bias might also exist.
CONCLUSION
The present systematic review and meta-analysis demonstrates that both taxane-based regimens have comparable efficacy for patients with MBC, and the paclitaxel-based regimen is associated with less toxicity and better tolerability, especially in older patients and when used in weekly regimens.
Topics: Antineoplastic Agents; Breast Neoplasms; Docetaxel; Female; Humans; Paclitaxel; Randomized Controlled Trials as Topic; Taxoids; Treatment Outcome
PubMed: 23216340
DOI: 10.1185/03007995.2012.756393 -
Frontiers in Endocrinology 2023Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative... (Meta-Analysis)
Meta-Analysis
Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.
BACKGROUND
Male testicular dysfunction is a considerable complication of anti-cancer therapies, including chemotherapy and radiotherapy, partly due to the increased oxidative stress caused by these treatments. Melatonin is an effective antioxidant agent that protects testicles against physical and toxic chemical stressors in animal models. This study aims to systematically review the melatonin's protective effects against anti-cancer stressors on rodential testicular tissue.
MATERIALS AND METHOD
An extensive search was conducted in Web of Science, Scopus, and PubMed for animal studies investigating exogenous melatonin's protective effects on rodent testicles exposed to anti-cancer chemicals and radiotherapeutic agents. Using the DerSimonian and Laird random-effect model, standardized mean differences and 95% confidence intervals were estimated from the pooled data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022355293).
RESULTS
The meta-analysis included 38 studies from 43 studies that were eligible for the review. Rats and mice were exposed to radiotherapy (ionizing radiations such as gamma- and roentgen radiation and radioactive iodine) or chemotherapy (methotrexate, paclitaxel, busulfan, cisplatin, doxorubicin, vinblastine, bleomycin, cyclophosphamide, etoposide, Taxol, procarbazine, docetaxel, and chlorambucil). According to our meta-analysis, all outcomes were significantly improved by melatonin therapy, including sperm quantity and quality (count, motility, viability, normal morphology, number of spermatogonia, Johnsen's testicular biopsy score, seminiferous tubular diameter, and seminiferous epithelial height), serum level of reproductive hormones (Follicle-Stimulating Hormone and testosterone), tissue markers of oxidative stress (testicular tissue malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, glutathione, caspase-3, and total antioxidant capacity), and weight-related characteristics (absolute body, epididymis, testis, and relative testis to body weights). Most SYRCLE domains exhibited a high risk of bias in the included studies. Also, significant heterogeneity and small-study effects were detected.
CONCLUSION
In male rodents, melatonin therapy was related to improved testicular histopathology, reproductive hormones, testis and body weights, and reduced levels of oxidative markers in testicular tissues of male rodents. Future meticulous studies are recommended to provide a robust scientific backbone for human applications.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022355293, identifier CRD42022355293.
Topics: Humans; Male; Animals; Rats; Mice; Melatonin; Antioxidants; Iodine Radioisotopes; Semen; Thyroid Neoplasms; Oxidative Stress; Body Weight
PubMed: 37701901
DOI: 10.3389/fendo.2023.1184745 -
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 -
Aging Feb 2022Paclitaxel remains the first-line chemotherapy regimen for many malignant tumors. However, prognosis and adverse events under different dosing regimens (one-week versus... (Meta-Analysis)
Meta-Analysis
Paclitaxel remains the first-line chemotherapy regimen for many malignant tumors. However, prognosis and adverse events under different dosing regimens (one-week versus three-week treatment) remain contradictory in many randomized controlled trials (RCTs). Here, we performed a comprehensive meta-analysis to measure the efficacy and toxicities of these two dosing regimens. Four databases were systematically retrieved. RCTs comparing two paclitaxel dosing regimens for advanced malignant tumors with assessable outcomes (e.g., overall survival (OS), progression-free survival (PFS), toxicities, response rates) were included. In total, 19 eligible RCTs involving 9 674 patients were included. Meta-analysis of pan-cancers revealed that weekly paclitaxel treatment was more beneficial regarding PFS compared to three-week paclitaxel treatment (hazard ratio (HR) = 0.90, 95% confidence interval (CI) = 0.82-0.99, = 0.02). Nevertheless, there was no significant difference in terms of OS between the two dosing regimens (HR = 0.98, 95%CI = 0.91-1.06, = 0.62) or other tested subgroups. In terms of serious adverse events, grade 3 or 4 (G3/4) neutropenia, G3/4 febrile neutropenia, G3/4 arthritis, and G3/4 alopecia occurred less often under weekly paclitaxel treatment. In summary, Weekly paclitaxel treatment demonstrates better PFS and fewer chemotherapy-induced hematological and non-hematological toxicities compared to the three-week paclitaxel regimen.
Topics: Carcinoma; Humans; Paclitaxel; Progression-Free Survival
PubMed: 35218640
DOI: 10.18632/aging.203919 -
Supportive Care in Cancer : Official... Jul 2022Prophylaxis against infusion-related reactions (IRR) from paclitaxel with steroids and antihistamines is a standard of care due to high rates of IRR. This systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prophylaxis against infusion-related reactions (IRR) from paclitaxel with steroids and antihistamines is a standard of care due to high rates of IRR. This systematic review and meta-analysis aimed to comprehensively summarize the evidence behind various prophylaxis strategies.
METHODS
EMBASE, MEDLINE, PubMed, and the Cochrane Register of Controlled Trials were searched (1946 to May 14, 2021). The primary outcomes were Grade 3/4 IRR and any-grade IRR. Secondary outcomes included treatment delay or discontinuation and adverse events secondary to pre-medications.
RESULTS
Of the 1285 unique citations, 26 studies were selected: 11 studies for quantitative analysis and 15 studies for qualitative analysis. Studies included randomized controlled trials and observational studies (n = 25-281). There was a non-significant benefit in favour of oral steroids starting 12 h prior to paclitaxel administration versus intravenous steroids immediately prior to paclitaxel administration for grade 3/4 IRRs, with a risk difference (RD) of 2% [95%CI 0 to 5%], any-grade IRR with a RD of 4% [95%CI: -1% to 9%] and treatment discontinuation with a RD of 1% [95%CI -1% to 2%]. For de-escalation strategies, a point-estimate for any-grade IRR was 0.44% [95% CI, 0 to 0.02, p = 0.98] and for grade 3/4 IRR was 3.1% (95% CI, 0.02 to 0.07, p = 0.11).
CONCLUSION
Although studies have high risk of bias and risk, differences between steroid routes of administration were small, there was a non-significant trend in favour of oral steroids. De-escalation strategies after two previous successful paclitaxel infusions have an overall low incidence rate of severe IRR and warrant further prospective clinical trials. Insufficient evidence remains to recommend for or against other interventions for the prevention of paclitaxel IRR.
Topics: Clinical Protocols; Humans; Paclitaxel; Steroids
PubMed: 35150312
DOI: 10.1007/s00520-022-06891-0