-
Cancers Aug 2021Therapy with gemcitabine and nab-paclitaxel (GNP) is the most commonly used palliative chemotherapy, but its advantage in the neoadjuvant setting remains unclear.... (Review)
Review
Therapy with gemcitabine and nab-paclitaxel (GNP) is the most commonly used palliative chemotherapy, but its advantage in the neoadjuvant setting remains unclear. Accordingly, our aim is to evaluate the impact of first-line neoadjuvant therapy with GNP in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). A systematic search for published studies until August 2020 was performed. The primary endpoint included resection and R0 resection rates in the intention-to-treat population. Secondary endpoints were response rate, survival and toxicity. Among 21 studies, 950 patients who received neoadjuvant GNP were evaluated. Treatment with GNP resulted in surgical resection and R0 resection rates as follows: 49% (95% CI 30-68%) and 36% (95% CI 17-58%) for BRPC and 16% (95% CI 7-26%) and 11% (95% CI 5-19%) for LAPC, respectively. The objective response rates and the median overall survival (mOS) ranged from 0 to 67% and 12 to 30 months, respectively. Neutropenia (range 5-77%) and neuropathy (range 0-22%) were the most commonly reported grade 3 to 4 adverse events. Neoadjuvant chemotherapy with GNP can be performed safely and with valuable effects in patients with BRPC and LAPC. The utility of GNP in comparison to FOLFIRINOX in the neoadjuvant setting requires further investigation in prospective randomized trials.
PubMed: 34503138
DOI: 10.3390/cancers13174326 -
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 -
European Urology Sep 2014The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although some studies suggest a benefit.
OBJECTIVE
To update the current evidence on the role of NC and AC for UTUC patients.
EVIDENCE ACQUISITION
We searched for all studies investigating NC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings prior to February 2014. A systematic review and meta-analysis were performed.
EVIDENCE SYNTHESIS
No randomized trials investigated the role of AC for UTUC. There was one prospective study (n=36) investigating adjuvant carboplatin-paclitaxel and nine retrospective studies, with a total of 482 patients receiving cisplatin-based or non-cisplatin-based AC after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS) was 0.43 (95% confidence interval [CI], 0.21-0.89; p=0.023) compared with those who received surgery alone. For disease-free survival (DFS), the pooled HR across two studies was 0.49 (95% CI, 0.24-0.99; p=0.048). Benefit was not seen for non-cisplatin-based regimens. For NC, two phase 2 trials demonstrated favorable pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) ≤ 93%. Across two retrospective studies investigating NC, there was a DSS benefit, with a pooled HR of 0.41 (95% CI, 0.22-0.76; p=0.005).
CONCLUSIONS
There appears to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is limited by the retrospective nature of studies and their relatively small sample size. NC appears to be promising, but more trials are needed to confirm its utility.
PATIENT SUMMARY
After a comprehensive search of studies examining the role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows that cisplatin-based adjuvant chemotherapy was beneficial for prolonging survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Humans; Kidney Neoplasms; Neoadjuvant Therapy; Paclitaxel; Survival Rate; Ureteral Neoplasms; Urothelium
PubMed: 24680361
DOI: 10.1016/j.eururo.2014.03.003 -
Thorax Jan 2002Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the... (Review)
Review
BACKGROUND
Lung cancer remains a devastating disease with few effective treatment options. Recent developments in chemotherapy have led to cautious optimism. This paper reviews the evidence on the clinical and cost effectiveness of four of the new generation drugs for patients with lung cancer.
METHODS
A systematic review of randomised controlled trials (RCTs) identified from 11 electronic databases (including Medline, Cochrane library and Embase), reference lists and contact with experts and industry was performed to assess clinical effectiveness of paclitaxel, docetaxel, gemcitabine and vinorelbine. Clinical effectiveness was assessed using the outcomes of patient survival, quality of life, and adverse effects. Cost effectiveness was assessed by development of a costing model and presented as incremental cost per life year saved (LYS) compared with best supportive care (BSC).
RESULTS
Of the 33 RCTs included, five were judged to be of good quality, 10 of adequate quality, and 18 of poor quality. Gemcitabine, paclitaxel, and vinorelbine as first line treatment and docetaxel as second line treatment appear to be more beneficial for non-small cell lung cancer than BSC and older chemotherapy agents, increasing patient survival by 2-4 months against BSC and some comparator regimes. These gains in survival do not appear to be at the expense of quality of life. Survival gains were delivered at reasonable levels of incremental cost effectiveness for vinorelbine, vinorelbine with cisplatin, gemcitabine, gemcitabine with cisplatin, and paclitaxel with cisplatin regimens compared with BSC.
CONCLUSION
Although the clinical benefits of the new drugs appear relatively small, their benefit to patients with lung cancer appears to be worthwhile and cost effective.
Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost of Illness; Cost-Benefit Analysis; Deoxycytidine; Docetaxel; Humans; Lung Neoplasms; Paclitaxel; Quality of Life; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Taxoids; Treatment Outcome; Vinblastine; Vinorelbine; Gemcitabine
PubMed: 11809985
DOI: 10.1136/thorax.57.1.20 -
Health Technology Assessment... Jan 2015Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line... (Comparative Study)
Comparative Study Meta-Analysis Review
Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for advanced recurrent or refractory ovarian cancer: a systematic review and economic evaluation.
BACKGROUND
Ovarian cancer is the fifth most common cancer in the UK, and the fourth most common cause of cancer death. Of those people successfully treated with first-line chemotherapy, 55-75% will relapse within 2 years. At this time, it is uncertain which chemotherapy regimen is more clinically effective and cost-effective for the treatment of recurrent, advanced ovarian cancer.
OBJECTIVES
To determine the comparative clinical effectiveness and cost-effectiveness of topotecan (Hycamtin(®), GlaxoSmithKline), pegylated liposomal doxorubicin hydrochloride (PLDH; Caelyx(®), Schering-Plough), paclitaxel (Taxol(®), Bristol-Myers Squibb), trabectedin (Yondelis(®), PharmaMar) and gemcitabine (Gemzar(®), Eli Lilly and Company) for the treatment of advanced, recurrent ovarian cancer.
DATA SOURCES
Electronic databases (MEDLINE(®), EMBASE, Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluations Database) and trial registries were searched, and company submissions were reviewed. Databases were searched from inception to May 2013.
METHODS
A systematic review of the clinical and economic literature was carried out following standard methodological principles. Double-blind, randomised, placebo-controlled trials, evaluating topotecan, PLDH, paclitaxel, trabectedin and gemcitabine, and economic evaluations were included. A network meta-analysis (NMA) was carried out. A de novo economic model was developed.
RESULTS
For most outcomes measuring clinical response, two networks were constructed: one evaluating platinum-based regimens and one evaluating non-platinum-based regimens. In people with platinum-sensitive disease, NMA found statistically significant benefits for PLDH plus platinum, and paclitaxel plus platinum for overall survival (OS) compared with platinum monotherapy. PLDH plus platinum significantly prolonged progression-free survival (PFS) compared with paclitaxel plus platinum. Of the non-platinum-based treatments, PLDH monotherapy and trabectedin plus PLDH were found to significantly increase OS, but not PFS, compared with topotecan monotherapy. In people with platinum-resistant/-refractory (PRR) disease, NMA found no statistically significant differences for any treatment compared with alternative regimens in OS and PFS. Economic modelling indicated that, for people with platinum-sensitive disease and receiving platinum-based therapy, the estimated probabilistic incremental cost-effectiveness ratio [ICER; incremental cost per additional quality-adjusted life-year (QALY)] for paclitaxel plus platinum compared with platinum was £24,539. Gemcitabine plus carboplatin was extendedly dominated, and PLDH plus platinum was strictly dominated. For people with platinum-sensitive disease and receiving non-platinum-based therapy, the probabilistic ICERs associated with PLDH compared with paclitaxel, and trabectedin plus PLDH compared with PLDH, were estimated to be £25,931 and £81,353, respectively. Topotecan was strictly dominated. For people with PRR disease, the probabilistic ICER associated with topotecan compared with PLDH was estimated to be £324,188. Paclitaxel was strictly dominated.
LIMITATIONS
As platinum- and non-platinum-based treatments were evaluated separately, the comparative clinical effectiveness and cost-effectiveness of these regimens is uncertain in patients with platinum-sensitive disease.
CONCLUSIONS
For platinum-sensitive disease, it was not possible to compare the clinical effectiveness and cost-effectiveness of platinum-based therapies with non-platinum-based therapies. For people with platinum-sensitive disease and treated with platinum-based therapies, paclitaxel plus platinum could be considered cost-effective compared with platinum at a threshold of £30,000 per additional QALY. For people with platinum-sensitive disease and treated with non-platinum-based therapies, it is unclear whether PLDH would be considered cost-effective compared with paclitaxel at a threshold of £30,000 per additional QALY; trabectedin plus PLDH is unlikely to be considered cost-effective compared with PLDH. For patients with PRR disease, it is unlikely that topotecan would be considered cost-effective compared with PLDH. Randomised controlled trials comparing platinum with non-platinum-based treatments might help to verify the comparative effectiveness of these regimens.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013003555.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cost-Benefit Analysis; Deoxycytidine; Dioxoles; Disease-Free Survival; Double-Blind Method; Doxorubicin; Female; Health Care Costs; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Ovarian Neoplasms; Paclitaxel; Polyethylene Glycols; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Risk Assessment; Survival Analysis; Tetrahydroisoquinolines; Topotecan; Trabectedin; Treatment Outcome; United Kingdom; Gemcitabine
PubMed: 25626481
DOI: 10.3310/hta19070 -
Journal of Vascular Surgery Dec 2020The comparison between paclitaxel-coated balloon (PCB) angioplasty and plain balloon angioplasty (PBA) for hemodialysis (HD) access stenosis or occlusion has not been... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The comparison between paclitaxel-coated balloon (PCB) angioplasty and plain balloon angioplasty (PBA) for hemodialysis (HD) access stenosis or occlusion has not been well investigated. The objectives of this systematic review and meta-analysis were to compare all-cause mortality, HD access primary patency, and circuit primary patency after endovascular maintenance procedures using PCB angioplasty vs PBA.
METHODS
MEDLINE, Embase, and Cochrane Databases were systematically searched to identify all the relevant studies on paclitaxel-coated devices for stenosis or thrombosis of HD access. A random effects model was applied to pool the effect measures. Dichotomous data were presented using an odds ratio (OR). Effect data were presented using pooled hazard ratio (HR) with 95% confidence interval (CI).
RESULTS
A total of 16 studies were included in this meta-analysis, 12 randomized controlled trials and 4 cohort studies involving 1086 patients who underwent endovascular treatment for HD access stenosis or occlusion. All-cause mortality rates at 6, 12, and 24 months after intervention were similar between the PCB and PBA groups (6 months: OR, 1.06 [95% CI, 0.38-2.96; P = .907; I = 19.2%]; 12 months: OR, 1.20 [95% CI, 0.66-2.16; P = .554; I = 0%]; 24 months: OR, 1.43 [95% CI, 0.83-2.45; P = .195; I = 0%]). There was a significant improvement of primary patency in the PCB group compared with the PBA group (HR, 0.47; 95% CI, 0.33-0.69; P < .001; I = 67.3%). This benefit was consistent with the analysis of randomized controlled trials, whereas cohort studies were excluded. Further subgroup analysis of target lesions demonstrated that primary patency was significantly higher in the PCB group than in the PBA group, not only for arteriovenous fistula (HR, 0.54; 95% CI, 0.30-0.98; P = .041; I = 76.8%) but also for central venous stenosis (HR, 0.39; 95% CI, 0.22-0.71; P = .002; I = 0%). The PCB group was associated with higher 6-month (OR, 0.40; 95% CI, 0.27-0.59; P < .001) and 24-month lesion primary patency (OR, 0.28; 95% CI, 0.11-0.72; P = .009) than PBA and was marginally associated with 12-month lesion primary patency (OR, 0.52; 95% CI, 0.26-1.03; P = .06). Circuit primary patency analysis showed a marginal trend toward better outcome in the PCB group (HR, 0.63; 95% CI, 0.40-1.00) but no statistical significance (P = .052).
CONCLUSIONS
This systematic review and meta-analysis demonstrated that PCB angioplasty is associated with significantly improved primary patency of arteriovenous fistula and central venous stenosis for HD access maintenance, with no evidence of increasing all-cause mortality based on short-term and midterm follow-up. Further large cohort study is needed to investigate long-term mortality.
Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Arteriovenous Shunt, Surgical; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coated Materials, Biocompatible; Equipment Design; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Paclitaxel; Recurrence; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency
PubMed: 32540324
DOI: 10.1016/j.jvs.2020.04.525 -
A systematic review of platinum and taxane resistance from bench to clinic: an inverse relationship.Cancer Treatment Reviews Dec 2007We undertook a systematic review of the pre-clinical and clinical literature for studies investigating the relationship between platinum and taxane resistance. Medline... (Review)
Review
We undertook a systematic review of the pre-clinical and clinical literature for studies investigating the relationship between platinum and taxane resistance. Medline was searched for (1) cell models of acquired drug resistance reporting platinum and taxane sensitivities and (2) clinical trials of platinum or taxane salvage therapy in ovarian cancer. One hundred and thirty-seven models of acquired drug resistance were identified. 68.1% of cisplatin-resistant cells were sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells were sensitive to cisplatin. A similar inverse pattern was observed for cisplatin vs. docetaxel, carboplatin vs. paclitaxel and carboplatin vs. docetaxel. These associations were independent of cancer type, agents used to develop resistance and reported mechanisms of resistance. Sixty-five eligible clinical trials of paclitaxel-based salvage after platinum therapy were identified. Studies of single agent paclitaxel in platinum-resistant ovarian cancer where patients had previously recieved paclitaxel had a pooled response rate of 35.3%, n=232, compared to 22% in paclitaxel naïve patients n=1918 (p<0.01, Chi-squared). Suggesting that pre-treatment with paclitaxel may improve the response of salvage paclitaxel therapy. The response rate to paclitaxel/platinum combination regimens in platinum-sensitive ovarian cancer was 79.5%, n=88 compared to 49.4%, n=85 for paclitaxel combined with other agents (p<0.001, Chi-squared), suggesting a positive interaction between taxanes and platinum. Therefore, the inverse relationship between platinum and taxanes resistance seen in cell models is mirrored in the clinical response to these agents in ovarian cancer. An understanding of the cellular and molecular mechanisms responsible would be valuable in predicting response to salvage chemotherapy and may identify new therapeutic targets.
Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Drug Resistance, Neoplasm; Female; Humans; Ovarian Neoplasms; Platinum Compounds; Taxoids
PubMed: 17881133
DOI: 10.1016/j.ctrv.2007.07.013 -
Journal of Endovascular Therapy : An... Apr 2016To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Meta-analysis of Randomized Controlled Trials of Paclitaxel-Coated Balloon Angioplasty in the Femoropopliteal Arteries: Role of Paclitaxel Dose and Bioavailability.
PURPOSE
To provide a qualitative analysis and quantitative synthesis of randomized controlled trials (RCTs) investigating paclitaxel-coated balloons (PCBs) in the femoropopliteal artery.
METHODS
PubMed, EMBASE, AMED, Scopus, CENTRAL, online content, and abstracts from international meetings were last screened in April 2015 for eligible RCTs using the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration's tool, and quality of evidence was evaluated with the GRADE system. Outcome measures included late lumen loss (LLL) at 6 months and event rates of major limb amputations, binary lesion restenosis, and target lesion revascularization (TLR). Pooled treatment effects were analyzed in a random effects model to account for clinical heterogeneity; the outcomes are presented as the rate ratios (RRs) and their 95% confidence intervals (CIs). Extensive meta-regression was performed to analyze potential confounders. The review was registered in the PROSPERO database (CRD42015023938; www.crd.york.ac.uk/PROSPERO).
RESULTS
Eleven RCTs with 1609 subjects (1403 claudicants and 206 patients with critical limb ischemia) with medium-length femoropopliteal lesions (mean range 5.1-11.9 cm) were included. There was consistently high-quality evidence supporting the clear superiority of PCBs in terms of reduced LLL (mean difference -0.89 mm, 95% CI -1.14 to -0.64, p<0.001), less binary restenosis (RR 0.47, 95% CI 0.37 to 0.61, p<0.001), and fewer TLR events (RR 0.33, 95% CI 0.22 to 0.49, p<0.001). Major amputations were rare in both active and control arms (pooled event rate: 0.7%, 95% CI 0.3% to 1.2%). Results were stable across all potential risk modifiers and in the presence of stents as well. There was high-quality evidence that the dose of paclitaxel was related to the magnitude of the treatment effect; standard dose (3.0-μg and 3.5-μg) PCBs were significantly more effective compared with low-dose 2-μg PCB in reducing both restenosis (RR 2.1, 95% CI 1.2 to 3.4, p<0.001) and TLR (RR 2.5, 95% CI 1.9 to 3.8, p<0.001).
CONCLUSION
PCBs reduce by more than half the rates of restenosis and TLR in the femoropopliteal artery regardless of stent placement. Biologic effect size may vary according to paclitaxel bioavailability.
Topics: Amputation, Surgical; Angioplasty, Balloon; Biological Availability; Cardiovascular Agents; Chi-Square Distribution; Coated Materials, Biocompatible; Constriction, Pathologic; Equipment Design; Femoral Artery; Humans; Limb Salvage; Odds Ratio; Paclitaxel; Peripheral Arterial Disease; Popliteal Artery; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Time Factors; Treatment Outcome; Vascular Access Devices; Vascular Patency
PubMed: 26823485
DOI: 10.1177/1526602815626557 -
Health Technology Assessment... 2001The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about... (Review)
Review
BACKGROUND
The incidence of lung cancer is declining following a drop in smoking rates, but it is still the leading cause of death from cancer in England and Wales, with about 30,000 deaths a year. Survival rates for lung cancer are poor everywhere, but they appear to be better in the rest of the European Community and the USA than in the UK. Only about 5 per cent of people with lung cancer survive for 5 years, and nearly all of these are cured by surgery after fortuitously early diagnosis. At present, only a small proportion of patients (probably about 5 per cent) with non-small-cell lung cancer are being given chemotherapy. Some centres treat a greater proportion.
OBJECTIVES
This review examines the clinical effectiveness and cost-effectiveness of four of the newer drugs - vinorelbine, gemcitabine, paclitaxel and docetaxel - used for treating the most common type of lung cancer (non-small-cell lung cancer). The first three drugs are used for first-line treatment, but at present docetaxel is used only after first-line chemotherapy has failed.
METHODS
This report was based on a systematic literature review and economic modelling, supplemented by cost data. RESULTS - NUMBER AND QUALITY OF STUDIES: A reasonable number of randomised trials were found - three for docetaxel, six for gemcitabine, five for paclitaxel and 13 for vinorelbine. The quality of the trials was variable but good overall. There was a wide range of comparators. Some trials compared chemotherapy with best supportive care (BSC), which involves care that aims to control symptoms, with palliative radiotherapy if needed, but not to prolong life. Others compared the newer drugs against previous drugs or combinations. RESULTS - SUMMARY OF BENEFITS: The gains in duration of survival with the new drugs are modest - a few months - but worthwhile in a condition for which the untreated survival is only about 5 months. There are also gains in quality of life compared with BSC, because on balance the side-effects of some forms of chemotherapy have less effect on quality of life than the effects of uncontrolled spread of cancer. RESULTS - COSTS: The total cost to the NHS of using these new drugs in England and Wales might be about GBP 10 million per annum, but is subject to a number of factors. There would be non-financial constraints on any increase in chemotherapy for the next few years, such as staffing; the number of patients choosing to have the newer forms of chemotherapy is not yet known; and the costs of the drugs may fall, for example, as generic forms appear. RESULTS - COST PER LIFE-YEAR GAINED: The available data did not provide an entirely satisfactory basis for cost-effectiveness calculations. The main problem was the lack of direct comparisons of the new drugs. In order to strengthen the analysis, three different modelling approaches were used: pairwise comparisons using trial data; cost-minimisation analysis, as if all the new regimens were of equal efficacy; and cost-effectiveness analysis pooling the results of several trials with different comparators, giving indirect comparisons of the new drugs by using BSC as the common comparator. A number of different scenarios were explored through extensive sensitivity analysis in each model. Outcomes were expressed in incremental cost per life-year saved or incremental cost, versus BSC. There was insufficient evidence from which to derive cost per quality-adjusted life-year. In first-line treatment, vinorelbine, gemcitabine, and the lower-dose paclitaxel plus cisplatin combinations generally performed well against BSC under a range of different scenarios and especially when given as a maximum of 3 cycles. Incremental cost per life-year gained (LYG) versus BSC varied depending on scenario, but baseline figures based on trial data and protocols were: single-agent vinorelbine, pound 2194 per LYG; vinorelbine plus cisplatin, pound 5206; single-agent gemcitabine, pound 5690; gemcitabine plus cisplatin, pound 10,041; and paclitaxel plus cisplatin, pound 8537. In second-line chemotherapy, docetaxel gave a cost per LYG of pound 17,546, again well within the range usually accepted as cost-effective. However, in routine care, the impact of therapy would be regularly reviewed, and continuation would depend on response, side-effects, patient choice and clinical judgement. Chemotherapy would be stopped in non-responders, making chemotherapy more cost-effective. A 'real-life' scenario in which 60 per cent of patients receive only 1 or 2 cycles of chemotherapy gives much lower costs per LYG, with single-agent gemcitabine, single-agent vinorelbine, and paclitaxel plus platinum appearing to be cost-saving compared with BSC; the incremental cost of gemcitabine plus cisplatin would be pound 2478 per LYG, and of vinorelbine plus cisplatin, pound 2808. At the very least, gains in duration of survival were achieved without diminution of quality of life (at best, they improved quality) and with relatively low incremental cost. Comparisons among the individual drugs should be viewed with caution because they have had to be based on indirect comparisons. RESULTS - LIMITATIONS OF THE ANALYSIS: Each of the three models had limitations. The cost-effectiveness estimates from the pairwise comparisons were based on single studies. The cost-minimisation analysis assumed that the regimens have equal efficacy in practice. The cost-effectiveness analysis had to be based on pooling data from individual trials. The costs of BSC, inpatient stay and outpatient visits were from Scottish data. Median rather than mean data on duration of survival have been used in the analysis, because most of the trials reported only median data. Median survival and number of drug cycles were calculated by averaging across a number of studies, rather than being reliant on one particular study. The costs of the less expensive antiemetics cited in the trials were omitted. The use of more modern and costly antiemetics would have a modest detrimental effect on cost-effectiveness. In the absence of published data, an estimate was made of the cost of side-effects of chemotherapy, in particular hospital admissions, and applied to all the new regimens. In practice, admissions related to side-effects and their respective costs are likely to vary by regimen.
CONCLUSIONS
The new drugs for non-small-cell lung cancer extend life by only a few months compared with BSC, but appear to do so without net loss in quality of life and at a cost per LYG that is much lower than for many other NHS activities. Depending on assumptions used, these new drugs range from being cost-effective, as conventionally accepted, to being cost-saving. CONCLUSIONS - IMPLICATIONS OF THE NEWER DRUGS: One of the present constraints on chemotherapy is availability of inpatient beds. The advent of newer and gentler forms of chemotherapy given on an outpatient basis would not only overcome this, but it would allow more patients to be treated. This might apply particularly to older patients. The treatment of more patients would increase workload for oncologists, cancer nurses and pharmacists. The Government has already announced increased expenditure on staff for cancer care. The previously pessimistic attitudes to chemotherapy in non-small-cell lung cancer are changing in the wake of the newer agents, and this shift is likely to increase referral. CONCLUSIONS - NEED FOR FURTHER RESEARCH: Recent advances in chemotherapy are welcome, but their effects remain small for patients with non-small-cell lung cancer. Much more research is needed into better drugs, better combinations, new ways of assessing the likelihood of response and especially direct comparisons between the new regimens. This research would be aided by having a greater proportion of patients involved in trials, but there will be infrastructure implications of increased participation.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cost-Benefit Analysis; Deoxycytidine; Docetaxel; England; Humans; Lung Neoplasms; Paclitaxel; Quality of Life; Survival Rate; Taxoids; Vinblastine; Vinorelbine; Wales; Gemcitabine
PubMed: 12065068
DOI: 10.3310/hta5320 -
Journal of Clinical Medicine Mar 2024: We conducted a systematic review and meta-analysis to examine the feasibility of paclitaxel-coated balloon (PCB) angioplasty for de novo lesions in patients with acute... (Review)
Review
Cardiovascular Outcomes after Paclitaxel-Coated Balloon Angioplasty versus Drug-Eluting Stent Placement for Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.
: We conducted a systematic review and meta-analysis to examine the feasibility of paclitaxel-coated balloon (PCB) angioplasty for de novo lesions in patients with acute coronary syndrome (ACS) by comparing with drug-eluting stent (DES) placement. : By a systematic literature search, nine (five randomized controlled, two retrospective propensity-score matched, and two retrospective baseline-balanced) studies comparing the midterm clinical and angiographic outcomes after PCB angioplasty and DES placement were included, yielding 974 and 1130 ACS cases in PCB and DES groups, respectively. Major adverse cardiac event (MACE) was defined as a composite of cardiac mortality (CM), all-cause mortality (ACM), myocardial infarction (MI), target vessel revascularization (TVR), and target lesion revascularization (TLR). Late luminal loss (LLL) and bleeding events (BLD) were also estimated. : The frequencies of MACE in PCB and DES groups were 8.42% and 10.62%, respectively. PCB angioplasty had no significant impacts on all of MACE (risk ratio: 0.90, 95%CI: 0.68-1.18, = 0.44), CM, ACM, MI, TVR, TLR, BLD, and LLL, compared to DES placement in random-effects model. : The present systematic review and meta-analysis showed the feasibility of PCB angioplasty for the de novo lesions in patients with ACS in comparison with DES placement by the emergent procedures.
PubMed: 38592314
DOI: 10.3390/jcm13051481