Safra Tamar, Rogowski Ori, Muggia Franco M
*Department of Oncology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel; †New York University Cancer Institute, New York University School of Medicine, New York, NY; and ‡Department of Internal Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel.
Int J Gynecol Cancer. 2014 Mar;24(3):488-95. doi: 10.1097/IGC.0000000000000086.
The treatment of recurrent epithelial ovarian cancer (rEOC) remains a major challenge because of the development of platinum resistance. To identify treatment regimens associated with better outcomes in BRCA mutation carriers compared with patients with nonhereditary (NH) disease, we summarized the experience after chemotherapy treatment of rEOC in 1 institution and compared the outcome in BRCA mutation carriers versus NH subsets.
We retrospectively analyzed 256 patient records with rEOC who were treated with second-, third-, and fourth-line treatment with the usual sequential regimens consisting of either pegylated liposomal doxorubicin (PLD), taxanes, gemcitabine, or topotecan (alone or in combination with platinum) between 2002 and 2012 at our institution. The analysis of founder mutations in 8 hotspots was performed. The outcome in BRCA mutation carriers was compared with that of patients with NH disease.
BRCA mutation carriers treated with PLD (with or without platinum) or with gemcitabine + platinum had improved progression-free survival (PFS) and a lower risk for disease progression (adjusted for age, line of treatment, and platinum sensitivity) compared with patients with NH disease. By contrast, treatment with taxanes (with or without platinum) or topotecan led to similar PFS in BRCA mutation carriers and in patients with NH disease. Under all treatment regimens, BRCA mutation carriers showed improved overall survival after adjusting for age, line of treatment, and platinum sensitivity.
This single-institution experience provides indications of an enhanced benefit in PFS for BRCA mutation carriers compared with patients with NH disease across a number of drug regimens (PLD, platinum, or gemcitabine + platinum) regardless of platinum sensitivity and line of therapy.
由于铂耐药性的出现，复发性上皮性卵巢癌（rEOC）的治疗仍然是一项重大挑战。为了确定与非遗传性（NH）疾病患者相比，BRCA突变携带者中具有更好预后的治疗方案，我们总结了一家机构中rEOC化疗治疗后的经验，并比较了BRCA突变携带者与NH亚组的预后。
我们回顾性分析了2002年至2012年期间在本机构接受二线、三线和四线治疗的256例rEOC患者记录，这些患者采用了聚乙二醇化脂质体阿霉素（PLD）、紫杉烷类、吉西他滨或拓扑替康（单独或与铂联合）组成的常规序贯方案。对8个热点区域的始祖突变进行了分析。将BRCA突变携带者的预后与NH疾病患者的预后进行了比较。
与NH疾病患者相比，接受PLD（含或不含铂）或吉西他滨+铂治疗的BRCA突变携带者无进展生存期（PFS）改善，疾病进展风险较低（根据年龄、治疗线数和铂敏感性进行调整）。相比之下，紫杉烷类（含或不含铂）或拓扑替康治疗在BRCA突变携带者和NH疾病患者中导致相似的PFS。在所有治疗方案下，在根据年龄、治疗线数和铂敏感性进行调整后，BRCA突变携带者的总生存期有所改善。
这一单一机构的经验表明，与NH疾病患者相比，BRCA突变携带者在多种药物方案（PLD、铂或吉西他滨+铂）中PFS获益增加，无论铂敏感性和治疗线数如何。
