A systematic review of taxane-containing regimens for metastatic breast cancer

Abstract

We compared the results of randomised trials comparing taxane-containing chemotherapy regimens with regimens not containing a taxane in women with metastatic breast cancer. The specialised register of the Cochrane Breast Cancer Group was searched in March 2004. Eligibility was assessed and data extracted from eligible studies by two reviewers. Hazard ratios (HR) were derived for time-to-event outcomes, and a fixed-effect model was used for meta-analysis. Tumour response rates were analysed as dichotomous variables. Of 21 eligible trials, 16 had published some results and 12 data on overall survival. An estimated 2621 deaths among 3643 women suggest a significant difference in overall survival in favour of taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.86 -1.00, P ¼ 0.05). The treatment effect on survival was similar if only trials of first-line chemotherapy were included, although not statistically significant. There appeared to be an advantage for taxanes in time to progression (HR 0.92, 95% CI 0.85 -0.99, P ¼ 0.02) and overall response (odds ratio (OR) 1.34, 95% CI 1.18 -1.52, Po0.001). There was significant heterogeneity across the trials (Po0.001), partly because of the varying efficacy of the comparator regimens. Taxane-containing regimens improved overall survival in women with metastatic breast cancer. Taxane-containing regimens are more effective than some, but not all, nontaxanecontaining regimens. British Journal of Cancer (2005) Taxanes are among the most active chemotherapy agents used in the management of metastatic breast cancer. Paclitaxel was identified in 1971 as part of a National Cancer Institute (NCI) programme that screened medicinal plants for potential anticancer activity, and was first used in clinical trials in 1983 (Breast cancer: taxane clinical perspectives, 1996). Docetaxel was synthesised in 1986 and is similar to paclitaxel in its mechanism of action.Initially, the use of taxanes was limited by hypersensitivity reactions, but once these were better managed (largely by premedication with steroids), taxane use became more frequent. Taxanes have become part of standard management in most western countries and are used as single agents or in combination with other chemotherapeutic drugs or the monoclonal antibody trastuzumab (Bernard-Marty et al, 2003).The effect of taxanes on survival compared with other drugs or drug combinations is unclear. We therefore conducted a systematic review and meta-analysis to identify and synthesise the results of randomised clinical trials comparing taxanecontaining chemotherapy regimens with regimens that did not contain a taxane. Prospectively, we asked the following questions:(Q1) Regimen A plus taxane vs Regimen A (e.g. doxorubicin plus docetaxel vs doxorubicin alone) (Q2) Regimen A plus taxane vs Regimen B (e.g. doxorubicin plus docetaxel vs doxorubicin plus cyclophosphamide) (Q3) Single agent taxane vs Regimen C (e.g. docetaxel vs doxorubicin plus cyclophosphamide).The planned outcome measures were survival (date randomised to...

Caveolin-1 Tyrosine Phosphorylation Enhances Paclitaxel-mediated Cytotoxicity

“…Clinical studies have shown that taxane-containing regimens are associated with a statistically significant improvement in overall survival compared with nontaxane-containing regimens; however, these regimens are associated with leukopenia and neurotoxicity (46). Considering the heterogeneity among individuals, it is essential to discover molecular biomarkers in breast cancer cells that could help improve the benefits of taxanes by increasing the efficacy-to-toxicity ratio.…”

Phase III trial of doxorubicin plus cyclophosphamide (AC), docetaxel, and alternating AC and docetaxel as front-line chemotherapy for metastatic breast cancer: Japan Clinical Oncology Group trial (JCOG9802)

“…Our results are consistent with the findings of a meta-analysis of taxanes based on all relevant clinical trials of first-line treatment in MBC, which showed that single-agent taxanes were worse than single-agent anthracyclines in terms of TTP, but not in terms of response rates or survival [12]. A systematic review of the Cochrane Database showed that taxane-based regimens were significantly better than non-taxane-based regimens for MBC in terms of OS, TTP, and overall response [13]. On subgroup analysis, D was associated with significantly improved OS, TTP, and overall response, whereas paclitaxel was not.…”

Symptoms: Chemotherapy-Induced Peripheral Neuropathy

“…Breast cancer-related drugs that often cause neuropathy include those used in the metastatic setting such as: platinating agents, vinca alkaloids, eribulin, and ixabepilone. Perhaps the most important class, however, are the taxanes which are commonly employed in both the curative setting and the metastatic setting (Ghersi et al 2005 ;Nowak et al 2004 ); a class of drugs with potential for serious and, at times, long-lasting neuropathy .…”