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The Cochrane Database of Systematic... Jun 2013Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy results in complete... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum-based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer.
OBJECTIVES
To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL).
SEARCH METHODS
In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, The Cochrane Central Register of Controlled Trails (CENTRAL, The Cochrane Library 2009, Issue 1), MEDLINE, EMBASE, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For this update, the searches were extended to October 2012.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression-free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention-to-treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs.
MAIN RESULTS
We included eight trials (1644 women). When all chemotherapy regimens were combined, meta-analysis indicated no significant difference in three-, five- and 10-year OS or PFS. For five-year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10) and for the five-year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10-year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three- and five-year OS rates have no significant difference between the two groups.
AUTHORS' CONCLUSIONS
There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required.
Topics: Antineoplastic Agents; Disease-Free Survival; Female; Humans; Maintenance Chemotherapy; Ovarian Neoplasms; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 23813336
DOI: 10.1002/14651858.CD007414.pub3 -
Arab Journal of Urology Mar 2021: To systematically review the use of drug-eluting stents (DES) and drug-coated balloons (DCB) in urology. (Review)
Review
OBJECTIVE
: To systematically review the use of drug-eluting stents (DES) and drug-coated balloons (DCB) in urology.
MATERIALS AND METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. PubMed, Scopus, Web of science and Cochrane Library online databases were searched in February 2019. Experimental and clinical studies, which included the placement of a DES or dilatation with DCB for investigating their potential use in the urinary tract for the management of ureteric or urethral pathologies, were included. The primary endpoint was to evaluate the current use of DES and DCB in urology.
RESULTS
A total of 29 articles were included in the systematic review. A total of 10 studies tested DES or DCB containing anti-proliferative agents (paclitaxel, zotarolimus, sirolimus, halofugione). Antibiotic agent-containing DES were tested in nine studies (triclosan, quinolones, teicoplanin, nitrofurantoin, silver sulfadiazine). A total of eight studies investigated the release of anti-inflammatory agents by DES (ketorolac, indomethacin, EW-7197). Another group studied heparin-eluting stents.
CONCLUSION
Despite the inconclusive outcomes of the three randomised controlled trials, drug-coated/eluting devices constitute a promising field in urology for the prevention of complications associated with conventional stents including pain and encrustation. Pre-clinical and studies have shown their ability to mitigate inflammation, inhibit re-stenosis and improve pain as indicated by declined use of anti-inflammatory drugs.: DES: drug-eluting stents; DCB: drug-coated balloons; DCS: drug-coated stents; HF: halofungione; MCP-1: monocyte chemoattractant protein 1; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PTCA: percutaneous transluminal coronary angioplasty; RANTES: regulated on activation, normal T-cell expressed and secreted; RCT: randomised controlled trial; USSQ, Ureteric Stent Symptoms Questionaire.
PubMed: 34104496
DOI: 10.1080/2090598X.2021.1885948 -
Current Cancer Drug Targets May 2009A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship... (Review)
Review
A systematic review of cell models of acquired drug resistance not involving genetic manipulation showed that 80% of cell models had an inverse resistance relationship between cisplatin and paclitaxel. Here we systematically review genetically modified cell lines in which the inverse cisplatin/paclitaxel resistance phenotype has resulted. This will form a short list of genes which may play a role in the mechanism of the inverse resistance relationship as well as act as potential markers for monitoring the development of resistance in the clinical treatment of cancer. The literature search revealed 91 genetically modified cell lines which report toxicity or viability/apoptosis data for cisplatin and paclitaxel relative to their parental cell lines. This resulted in 26 genes being associated with the inverse cisplatin/paclitaxel phenotype. The gene with the highest number of genetically modified cell lines associated with the inverse resistance relationship was BRCA1 and this gene is discussed in detail with reference to chemotherapy response in cell lines and in the clinical treatment of breast, ovarian and lung cancer. Other genes associated with the inverse resistance phenotype included dihydrodiol dehydrogenase (DDH) and P-glycoprotein. Genes which caused cross resistance or cross sensitivity between cisplatin and paclitaxel were also examined, the majority of these genes were apoptosis associated genes which may be useful for predicting cross resistance. We propose that BRCA1 should be the first of a panel of cellular markers to predict the inverse cisplatin/paclitaxel resistance phenotype.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Antineoplastic Agents; BRCA1 Protein; Cell Line, Tumor; Cisplatin; Female; Genes, BRCA1; Humans; Neoplasms; Oxidoreductases; Paclitaxel; Phenotype; Treatment Outcome
PubMed: 19442054
DOI: 10.2174/156800909788166592 -
Journal of the Peripheral Nervous... Sep 2023Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be... (Review)
Review
BACKGROUND AND AIMS
Several widely used medications, with a relevant efficacy profile, are toxic to the peripheral nervous system and an even larger number of agents are suspected to be neurotoxic. There are concerns about the use of these drugs in patients with Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy. This review provides evidence-based updated recommendations on this clinically relevant topic.
METHODS
A systematic review of the available studies/reports written in English was performed from July to September 2022 including in the search string all reported putative neurotoxic drugs.
RESULTS
The results of our systematic review provide evidence-based support for the statement that use of vincristine, and possibly paclitaxel, can occasionally induce an atypical, and more severe, course of drug-related peripheral neurotoxicity in CMT patients. It is therefore reasonable to recommend caution in the use of these compounds in CMT patients. However, no convincing evidence for a similar recommendation could be found for all other drugs.
INTERPRETATION
It is important that patients with CMT are not denied effective treatments that may prolong life expectancy for cancer or improve their health status if affected by non-oncological diseases. Accurate monitoring of peripheral nerve function in CMT patients treated with any neurotoxic agent remains mandatory to detect the earliest signs of neuropathy worsening and atypical clinical courses. Neurologists monitoring CMT patients as part of their normal care package or for natural history studies should keep detailed records of exposures to neurotoxic medications and support reporting of accelerated neuropathy progression if observed.
Topics: Humans; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Neoplasms; Neurotoxicity Syndromes
PubMed: 37249082
DOI: 10.1111/jns.12566 -
The Annals of Pharmacotherapy Aug 2022Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an innovative form of taxane that has superior antitumor effects; however, the safety profile between... (Meta-Analysis)
Meta-Analysis
Adverse Event Profile for Nanoparticle Albumin-Bound Paclitaxel Compared With Solvent-Based Taxanes in Solid-Organ Tumors: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
BACKGROUND
Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is an innovative form of taxane that has superior antitumor effects; however, the safety profile between nab-paclitaxel and traditional taxanes remains controversial.
OBJECTIVE
To determine the burden of adverse events (AEs) in patients with multiple malignancies receiving nab-paclitaxel compared with that in patients receiving traditional taxanes.
METHODS
Randomized clinical trials comparing nab-paclitaxel with traditional taxanes (solvent-based paclitaxel [sb-paclitaxel] or docetaxel) in the treatment of primary solid-organ malignancies were included if AEs were reported as an outcome. Statistical analyses were conducted to calculate the summary odds ratio (OR) of the relevant adverse outcomes related to nab-paclitaxel and traditional taxanes. Prespecified subgroup analyses based on intervention and doses, primary tumor sites, and different ethnic groups were also performed.
RESULTS
Twelve clinical trials were included in the meta-analysis. Grade 3/4 anemia, thrombocytopenia, and neurotoxicity were more frequent with nab-paclitaxel than with traditional taxanes. Nab-paclitaxel at 100 or 125 mg/m/w dosage was associated with fewer or similar grade 3/4 specific AEs. Allergy was less common with nab-paclitaxel. The median recovery times of neurotoxicity were 25, 64, and 37 days in patients receiving nab-paclitaxel, sb-paclitaxel, and docetaxel, respectively. Elevated incidences of specific AEs were more common in breast cancer and non-Asian patients than in other malignancies and ethnic groups, respectively.
CONCLUSION AND RELEVANCE
Nab-paclitaxel increased the risk of hematologic and non-hematologic AEs in general, but anaphylaxis was less common, and the recovery duration of neurotoxicity was shorter. Weekly administration of nab-paclitaxel at a lower dosage provided better tolerance.
Topics: Albumin-Bound Paclitaxel; Albumins; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Docetaxel; Female; Humans; Nanoparticles; Paclitaxel; Randomized Controlled Trials as Topic; Solvents; Taxoids
PubMed: 34963337
DOI: 10.1177/10600280211058385 -
Health Technology Assessment... Oct 2008To identify the expected delay between publication of conference abstracts and full publication of results from trials of new anti-cancer agents for breast cancer and to... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To identify the expected delay between publication of conference abstracts and full publication of results from trials of new anti-cancer agents for breast cancer and to identify whether there are any apparent biases in publication and reporting.
DATA SOURCES
Major electronic databases were searched to identify randomised controlled trials (RCTs) of the selected interventions for the treatment of breast cancer.
REVIEW METHODS
A systematic review was conducted according to standard methods. Data were extracted from the included studies using a predesigned and piloted data extraction template.
RESULTS
Six anti-cancer treatments for breast cancer were included in the review: docetaxel, paclitaxel, trastuzumab, gemcitabine, lapatinib and bevacizumab. The literature searches generated 1556 references, from which 71 publications were retrieved and screened for inclusion. Screening identified 41 publications of 18 RCTs with at least one arm of treatment meeting the inclusion criteria for the review. Of the 18 included RCTs, only four publications (from three RCTs) reported the same outcomes in both an abstract and a full publication. Time between the abstract and full publication was 5 months in two cases, 7 months in one case and 19 months in one case (overall mean delay = 9 months). Eleven trials were identified that have not currently published in a full publication the data presented in an abstract or conference proceeding. The duration between publication of the abstracts and the end of August 2007 varied from 3 months to 38 months (mean delay 16.5 months). The longest delays in publication were for trials investigating gemcitabine (38 months) or bevacizumab (33 months). Observational analysis of the published and unpublished trials did not indicate any particular biases in terms of whether positive results were more likely to be fully published than non-significant ones.
CONCLUSIONS
It was surprising that only three of the 18 relevant RCTs had one or more full papers that reported the same outcome measures (and stage of analysis) as an earlier conference abstract. However, a limitation of this review is the small number of studies included. With a larger sample size than that in the present report, investigation into the effect of publication delay on decision-making might be feasible. Future research should include extension of this work to other anti-cancer drugs and investigation into the reasons for lengthy delays to full publication noted for some trials.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Breast Neoplasms; Consensus Development Conferences as Topic; Databases, Bibliographic; Deoxycytidine; Docetaxel; Female; Humans; Lapatinib; Paclitaxel; Publication Bias; Publishing; Quinazolines; Randomized Controlled Trials as Topic; Taxoids; Technology Assessment, Biomedical; Time; Trastuzumab; Gemcitabine
PubMed: 18831948
DOI: 10.3310/hta12320 -
European Review For Medical and... Sep 2022Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis.
OBJECTIVE
Multi-agent regimens such as Folfirinox and gemcitabine plus nab-paclitaxel have shown significant improvements compared with single-agent gemcitabine as neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic cancer. However, the efficacy and safety of Folfirinox and GNP as NAC for BRPC and LAPC is still controversial.
MATERIALS AND METHODS
The eligible studies including prospective, retrospective, and randomized controlled trial related to Folfirinox and GNP as NAC for patients with BRPC or LAPC up to March 2022 were searched and assessed. Pooled analysis for chemotherapy response rate, resection rate, R0 resection rate, progress free survival, overall survival, and grade 3/4 events of toxicity were performed in the study.
RESULTS
Eight studies were included in this meta-analysis. Compared with GNP, Folfirinox had higher resection rate (HR=0.82; 95% CI 0.59-1.14) and R0 resection rate (HR=0.77; 95% CI 0.60-0.97), better PFS (HR=0.78; 95% CI 0.55-1.12) and OS (HR=0.68; 95% CI 0.46-0.99), and without increasing severe toxicity rate (HR=0.95; 95% CI 0.71-1.28). There are no differences in rate of stable disease (HR=1.06; 95% CI 0.92-1.22) and partial/complete regression (HR=0.85; 95% CI 0.59-1.23) between two groups.
CONCLUSIONS
Higher resection and R0 resection rate and better PFS and OS results were obtained in Folfirinox group compared with GNP group for patients with BRPC and LAPC. There was no increased severe toxicity rate for Folfirinox compared with GNP.
Topics: Albumins; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Oxaliplatin; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Retrospective Studies; Gemcitabine
PubMed: 36111933
DOI: 10.26355/eurrev_202209_29656 -
Journal of Clinical Oncology : Official... Aug 2016To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer. (Review)
Review
PURPOSE
To provide evidence-based recommendations to oncologists and others for the treatment of patients with metastatic pancreatic cancer.
METHODS
American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts to conduct a systematic review of the literature from April 2004 to June 2015. Outcomes were overall survival, disease-free survival, progression-free survival, and adverse events.
RESULTS
Twenty-four randomized controlled trials met the systematic review criteria.
RECOMMENDATIONS
A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. Goals of care, patient preferences, treatment response, psychological status, support systems, and symptom burden should guide decisions for treatments. A palliative care referral should occur at first visit. FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin; favorable comorbidity profile) or gemcitabine plus nanoparticle albumin-bound (NAB) -paclitaxel (adequate comorbidity profile) should be offered to patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 1 based on patient preference and support system available. Gemcitabine alone is recommended for patients with ECOG PS 2 or with a comorbidity profile that precludes other regimens; the addition of capecitabine or erlotinib may be offered. Patients with an ECOG PS ≥ 3 and poorly controlled comorbid conditions should be offered cancer-directed therapy only on a case-by-case basis; supportive care should be emphasized. For second-line therapy, gemcitabine plus NAB-paclitaxel should be offered to patients with first-line treatment with FOLFIRINOX, an ECOG PS 0 to 1, and a favorable comorbidity profile; fluorouracil plus oxaliplatin, irinotecan, or nanoliposomal irinotecan should be offered to patients with first-line treatment with gemcitabine plus NAB-paclitaxel, ECOG PS 0 to 1, and favorable comorbidity profile, and gemcitabine or fluorouracil should be offered to patients with either an ECOG PS 2 or a comorbidity profile that precludes other regimens. Additional information is available at www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Communication; Evidence-Based Medicine; Humans; Pain Management; Palliative Care; Pancreatic Neoplasms; Patient Care Planning; Patient Care Team; Symptom Assessment
PubMed: 27247222
DOI: 10.1200/JCO.2016.67.1412 -
Health Technology Assessment... 2001Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the... (Comparative Study)
Comparative Study Review
BACKGROUND
Ovarian cancer is the most common gynaecological cancer with an annual incidence of 21.6 per 100,000 in England and Wales. Due to the often asymptomatic nature of the early stages of the disease, most cases are not detected until the advanced stages. Consequently, the prognosis after diagnosis is poor and the 5-year survival rate in the UK is only about 30%. Current recommendations suggest that first-line chemotherapy for ovarian cancer should involve paclitaxel and platinum (Pt)-based therapy (cisplatin/ carboplatin), however, most patients develop resistant or refractory disease and require second-line therapy. Patients may respond to re-challenge with Pt-agents if the treatment-free interval is > 6 months, but an alternative is often required. Topotecan is one of six drugs currently licensed in the UK for second-line therapy, and recent reviews suggest that it has modest efficacy in the treatment of advanced disease and performs favourably against paclitaxel. However, these reviews are based on a limited number of reports mainly consisting of non-randomised Phase I and II studies.
OBJECTIVES OF THE REVIEW
To examine the clinical effectiveness and cost-effectiveness of oral and intravenous topotecan (Hycamtin, SmithKline Beecham, UK) for the treatment of all stages of ovarian cancer.
SEARCH STRATEGY
Sixteen electronic databases from inception to September 2000 and Internet resources were searched, in addition to the bibliographies of retrieved articles and submissions from pharmaceutical companies.
INCLUSION AND EXCLUSION CRITERIA
Two reviewers independently screened all titles/abstracts and included/excluded studies based on full copies of manuscripts. Any disagreements were resolved through discussion. Only randomised controlled trials (RCTs) and full economic evaluations comparing topotecan to non-topotecan regimens were included. All stages of therapy and disease were considered, and the outcomes included were survival, response, symptom relief, quality of life, adverse effects and costs.
METHODS
DATA EXTRACTION STRATEGY: Data were extracted into an Access database by one reviewer and checked by a second. Any disagreements were resolved through discussion.
METHODS
QUALITY ASSESSMENT STRATEGY: Two reviewers, using specified criteria, independently assessed the quality of the clinical effectiveness studies and the economic evaluations. Any disagreements were resolved through discussion.
METHODS
ANALYSIS STRATEGY: Due to the limited number of studies included in the review and the fact that they compared topotecan with different comparators, the out-come data could not be pooled statistically. Clinical effectiveness data are discussed separately under the different outcome subheadings. For time-to-event data, hazard ratios with 95% confidence intervals are presented where available, and for the remaining outcomes, relative risks are reported or calculated where sufficient data were available. Relative risk data are also presented in the form of Forest plots without pooled estimates. Economic data are presented in the form of a summary and critique of the evidence, and a grading (A-I) assigned to each study indicating the direction and magnitude of the cost-effectiveness data.
INCLUDED STUDIES
A total of 568 titles/abstracts were identified and screened for relevance. Full copies of 72 papers were assessed and seven published manuscripts reporting details of two studies of clinical effectiveness and one economic evaluation were included. Further details of the two clinical effectiveness studies and two new economic evaluations were identified from confidential company submissions. Overall, two international multicentre RCTs of effectiveness comparing topotecan with paclitaxel (trial 039) and topotecan with caelyx (trial 30-49) were included in the review. The three economic evaluations included in the review comprised one cost-minimisation analysis (CMA) comparing topotecan with caelyx, one cost-consequences analysis (CCA) comparing topotecan with paclitaxel, etoposide and altretamine and one cost-effectiveness analysis (CEA) comparing topotecan with paclitaxel.
RESULTS
QUALITY OF CLINICAL EFFECTIVENESS DATA: Both clinical effectiveness studies (trial 30-49 and 039) were of reasonable quality, although it was unclear whether either performed valid intention-to-treat analyses. In addition, trial 30-49 failed to state whether the outcome assessors were blinded to treatment allocation. RESULTS --QUALITY OF ECONOMIC EVALUATIONS: The CCA (comparing topotecan with three comparators) was of poor quality and of little relevance to the UK NHS. The CMA and CEA were of reasonable quality overall and relevant to the UK NHS. However, both, in particular the CEA, suffered from methodological problems, and thus their findings should be interpreted with caution.
RESULTS
ASSESSMENT OF CLINICAL EFFECTIVENESS: The assessment of clinical effectiveness was based on limited data. Only two trials with a total of 709 participants were identified. In general, with a few minor exceptions, there were no statistically significant differences between topotecan and paclitaxel, or topotecan and caelyx in survival, response rate, median time to response, median duration of response and quality of life. Significant differences that were reported were mainly identified in subgroup analyses (Pt-sensitive disease and disease without ascites) of questionable validity and their relevance to a general advanced ovarian cancer patient population undergoing second-line chemotherapy is unclear. However, statistically significant differences were observed in the incidence of adverse effects. Topotecan was associated with increased incidences of haematological toxicities (including neutropenia, leukopenia, anaemia and thrombocytopenia), alopecia, nausea and vomiting. Caelyx-treated patients suffered from significantly increased incidences of Palmar-Plantar erythrodysesthesia, stomatitis, mucous membrane disorders and skin rashes. Paclitaxel was associated with significant increases in alopecia, arthralgia, myalgia, neuropathy, paraesthesiae, skeletal pain and flushing.
RESULTS
ASSESSMENT OF COST-EFFECTIVENESS: The assessment of cost-effectiveness was also based on limited data, with three evaluations identified, one of which was not relevant. The two remaining studies, comparing topotecan with paclitaxel (CEA) and topotecan with caelyx (CMA), both used effectiveness data from multicentre RCTs and based their costs on 1999/2000 UK sources. The evaluations were conducted from a UK NHS perspective and findings presented in GB pounds/Euros. Topotecan for the second-line treatment of advanced ovarian cancer was shown to be more cost-effective than paclitaxel (32,513 GB pounds versus 46,186 GB pounds per person in terms of any response (complete or partial), incremental cost-effectiveness = 3065 GB pounds) in all respects except cost per time without toxicity or symptoms, but less cost-effective than caelyx (14,023 GB pounds versus 9979 GB pounds per person regardless of whether the patient responded). However, direct comparisons of the cost findings between the two studies is difficult because they used different designs, different time horizons for the cost analyses and the findings were presented as costs per person for only patients who responded in one study (topotecan versus paclitaxel) and costs per person regardless of whether they responded in the other study (topotecan versus caelyx).
CONCLUSIONS
This review indicates that there is little evidence in the form of RCTs on which to base an assessment of the effectiveness of topotecan as second-line therapy for advanced ovarian cancer. The evidence suggests there were no statistically significant differences overall between topotecan and paclitaxel, or topotecan and caelyx in clinical outcomes. However, statistically significant differences were observed in the incidence of adverse effects. The clinical significance of the findings is not discussed. Overall, the effects of topotecan could at best be described as modest, but the alternative agents offer no real advantages except fewer side-effects and possibly improved cost-effectiveness. Both of the clinical effectiveness studies on which this evidence is based had methodological flaws, the most serious being the lack of a blinded assessor in the topotecan versus caelyx trial, which is important for unbiased assessment of response outcomes. The economic evaluations also suffered from a number of potential problems.
CONCLUSIONS
RECOMMENDATIONS FOR RESEARCH: Further good quality RCTs and CEAs are required comparing topotecan with other licensed and potentially useful (soon to be licensed) second-line treatments for ovarian cancer. At present, it is difficult to make any decisions about topotecan and other drugs for second-line therapy without good quality direct comparisons. In view of the ongoing studies identified, an update of the current review should be considered in approximately 18 months (Summer 2002) or possibly sooner if the recently commissioned National Institute for Clinical Excellence review of caelyx for ovarian cancer identifies additional data relevant to topotecan.
Topics: Antineoplastic Agents; Cost-Benefit Analysis; Female; Humans; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Technology Assessment, Biomedical; Topotecan
PubMed: 11701100
DOI: 10.3310/hta5280 -
Annals of Palliative Medicine Jul 2022Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic review of studies to identify the optimal taxanes for selection in clinical practice.
METHODS
We enrolled studies if they enrolled adults (age ≥18) with breast cancer, compared Nab-P (at any dose) to conventional paclitaxel or docetaxel, provided information on survival data, the response rate, or adverse events, were randomized controlled trials, case-control studies, or cohort studies, and were published in English (including those published online, ahead of the print publication). Cochrane Collaboration tool and Newcastle-Ottawa scale were used for bias-risk assessment. Grading of recommendations assessment, development, and evaluation approach were adopted for the quality of evidence evaluation. The outcomes included the overall response rate, pathological complete response rate, progression-free survival, overall survival, allergic reaction, leukopenia, neutropenia, and sensory neuropathy.
RESULTS
A total of 20 eligible clinical studies comprising 11,046 patients were included in the analysis. No significant publication bias was observed based on a visual inspection of the funnel plots for progressionfree survival (PFS), and overall survival (OS). Compared to the conventional taxanes group (n=2,743), the Nab-P group (n=1,680) had a significantly higher ORR (RR =1.21, 95% CI: 1.07-1.37; P=0.003) and pCR (RR =1.33, 95% CI: 1.17-1.51; P<0.001). The Nab-P group also had a lower risk of disease progression and death than the conventional taxanes group (HR =0.89, P=0.269). Additionally, the Nab-P group had fewer treatment-related allergic reactions (RR =0.74, 95% CI: 0.59-0.93; P=0.009) and less grade ≥4 neutropenia (RR =0.39, 95% CI: 0.20-0.77; P=0.007) than the conventional taxanes group. The incidence of any-grade of neutropenia and sensory neuropathy were significantly higher in the Nab-P group than the conventional taxanes group (P=0.009 and P<0.001, respectively).
DISCUSSION
The Nab-P in all stages of breast cancer patients had significantly better efficacy and tolerance than the conventional taxanes. Moreover, preventive strategies for reducing the incidence of Nab-P induced sensory neuropathy should be explored in future studies.
Topics: Adult; Albumin-Bound Paclitaxel; Breast Neoplasms; Female; Humans; Nanoparticles; Neutropenia; Paclitaxel; Randomized Controlled Trials as Topic; Taxoids
PubMed: 35927773
DOI: 10.21037/apm-22-690