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

Tan, D.S.P., Yap, T.A., Hutka, M., Roxburgh, P. , Ang, J., Banerjee, S., Grzybowska, E., Gourley, C., Gore, M.E. and Kaye, S.B. (2013) Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer. European Journal of Cancer, 49(6), pp. 1246-1253. (doi: 10.1016/j.ejca.2012.11.016)

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Abstract

<p>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.</p> <p>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.</p> <p>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).</p> <p>Conclusions: These data provide the first clinical evidence that paclitaxel monotherapy is active in BMOC and may be more effective in platinum-sensitive BMOC.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Roxburgh, Dr Patricia
Authors: Tan, D.S.P., Yap, T.A., Hutka, M., Roxburgh, P., Ang, J., Banerjee, S., Grzybowska, E., Gourley, C., Gore, M.E., and Kaye, S.B.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:European Journal of Cancer
ISSN:0959-8049

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