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Eur J Cancer. 2013 Apr;49(6):1246-53. doi: 10.1016/j.ejca.2012.11.016. Epub 2012 Dec 19.

Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer.

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1
Royal Marsden NHS Foundation Trust, Sutton, Surrey SM2 5PT, United Kingdom.

Abstract

INTRODUCTION:

Preclinical data suggest that BRCA1 and BRCA2 (BRCA1/2)-mutated ovarian cancers (BMOC) are exquisitely sensitive to platinum-salts, but resistant to microtubule-stabilizing anticancer agents. The clinical relevance of these preclinical data is unclear, since there are currently no published data on the efficacy of single-agent taxane chemotherapy in patients with BMOC. A retrospective study was undertaken to investigate the clinical effects of paclitaxel monotherapy in patients with BMOC.

METHODS:

Clinical data on responses and progression-free-survival (PFS) following paclitaxel (3-weekly/weekly) monotherapy in BMOC patients were collected from four cancer centres. Antitumour response was defined as RECIST partial or complete response (PR/CR), and clinical benefit was defined as PR/CR and stable disease (SD) lasting at least 18 weeks. Comparisons of the rate and duration of response and clinical benefit between categorical variables (e.g. platinum-sensitive versus platinum-resistant patients) were undertaken.

RESULTS:

We identified 26 BMOC patients who received paclitaxel monotherapy for relapsed disease, of which 15/26 (58%) were platinum-sensitive and 11/26 (42%) were platinum-resistant. The response rate to paclitaxel monotherapy was 46% (12/26). Clinical benefit rate was significantly higher in platinum-sensitive than platinum-resistant patients (80% versus 36%, p=0.04). BMOC patients with platinum-sensitive disease had significantly longer median PFS compared with platinum-resistant patients (42 versus 21 weeks, p=0.003).

CONCLUSIONS:

These data provide the first clinical evidence that paclitaxel monotherapy is active in BMOC and may be more effective in platinum-sensitive BMOC.

PMID:
23265709
DOI:
10.1016/j.ejca.2012.11.016
[Indexed for MEDLINE]
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