Ovarian Cancer in BRCA Mutation Carriers: Improved Outcome After Intraperitoneal (IP) Cisplatin
- 482 Downloads
Ovarian cancer arising in women with BRCA mutations is known to have a more favorable outcome and to be more responsive to platinum-based regimens than in those without a hereditary background. We analyze our previously published intraperitoneal (IP) studies in relation to BRCA mutation status and update their outcomes.
Among 62 patients with ovarian cancer enrolled in IP platinum doublet studies in clinical trials (with etoposide (n = 18), with floxuridine (n = 30), and with topotecan (n = 14)), a deleterious BRCA mutation was eventually identified in 10 patients. The outcomes in these BRCA mutation carriers are described and compared with survival of others in respective trials.
Ten patients that were confirmed to have BRCA mutations—all with high-grade and stages IIC to IV disease—survived a median of 10 years (range: 4–18+) after receiving IP cisplatin-based regimens. Two continue with no evidence of disease since their IP treatment, while four others remain alive with recurrences after 8, 9, 10, and 11 years, respectively.
This experience suggests that IP cisplatin leads to favorable long term outcomes in advanced ovarian cancer in women with defective homologous recombination (i.e., with deleterious BRCA mutations). Whether such cisplatin dose-intensification from IP relative to (intravenous) IV drug administration leads to superior results in these mutation carriers requires further study.
KeywordsOvarian Cancer Cancer Stem Cell BRCA Mutation Topotecan BRCA Mutation Carrier
- 6.Rubin SC, Blackwood MA, Bandera C, Behbakht K, Benjamin I, Rebbeck TR, Boyd J. BRCA1, BRCA2, and hereditary nonpolyposis colorectal cancer gene mutations in an unselected ovarian cancer population: relationship to family history and implications for genetic testing. Am J Obstet Gynecol. 1998;178(4):670–7.PubMedCrossRefGoogle Scholar
- 14.Lesnock J, Darcy K, Tian C, et al. Association between reduced BRCA1 expression and survival in patients with sporadic epithelial ovarian cancer treated with intraperitoneal versus intravenous cisplatin and paclitaxel: a Gynecologic Oncology Group Study. Gynecol Oncol. 2010;116(3):S3 (abstract 4).CrossRefGoogle Scholar
- 22.Safra T, Wei-Chu VL, Berman T, et al. BRCA mutations and outcome in epithelial ovarian cancer: experience in ethnically diverse groups. Ann Oncol. 2013(supplement) (in press).Google Scholar
- 24.National Cancer Institute (2006). NCI issues clinical announcement for preferred method of treatment for advanced ovarian cancer. http://www.cancer.gov/newscenter/pressreleases/2006/ipchemotherapyrelease. Accessed 2 April 2012.
- 33.ClinicalTrials.gov (2012) Bevacizumab and intravenous or intraperitoneal chemotherapy in treating patients with stage II, stage III, or stage IV ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer. http://www.clinicaltrials.gov/ct2/show/NCT00951496?term=GOG&rank=11. Accessed 22 July 2012.