Division of Gynecologic Oncology, The University of Pennsylvania Hospitals, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Gynecol Oncol. 2011 Dec;123(3):486-91. doi: 10.1016/j.ygyno.2011.08.032. Epub 2011 Sep 25.
Ten percent of ovarian cancer is attributed to hereditary syndromes, most commonly to mutations in the BRCA1 or BRCA2 genes. These cancers are characterized by a prolonged sensitivity to platinum agents in spite of presentation at advanced stages. We hypothesized that women with BRCA-associated ovarian cancer would also show a high response rate to pegylated liposomal doxorubicin (Doxil).
A retrospective cohort study was conducted to compare the response rate, progression-free, and overall survival among women with BRCA-associated or sporadic ovarian cancer who were treated with Doxil.
A response to Doxil was seen in 13 of 23 patients with BRCA mutations (56.5%; 3 by RECIST criteria and 10 by CA125 levels) compared with only 8 of 41 women with non-hereditary cancers (19.5%; 2 by RECIST criteria and 6 by CA125 levels; p=0.004). This was associated with an improved progression-free and overall survival as measured from the time of Doxil administration. Notably, platinum sensitivity did not directly correlate with a response to Doxil.
Women with BRCA-associated ovarian tumors demonstrate a greater sensitivity to cytotoxic therapy with Doxil than has previously been reported in unselected cases.
10%的卵巢癌归因于遗传性综合征,最常见的是 BRCA1 或 BRCA2 基因突变。这些癌症的特点是对铂类药物的敏感性延长,尽管表现为晚期。我们假设 BRCA 相关卵巢癌患者对聚乙二醇脂质体阿霉素(多柔比星脂质体)也会有很高的反应率。
进行了一项回顾性队列研究,比较了接受多柔比星脂质体治疗的 BRCA 相关和散发性卵巢癌患者的反应率、无进展生存期和总生存期。
在 23 名携带 BRCA 突变的患者中,有 13 名(56.5%;3 名根据 RECIST 标准,10 名根据 CA125 水平)对多柔比星脂质体有反应,而在 41 名非遗传性癌症患者中,只有 8 名(2 名根据 RECIST 标准,6 名根据 CA125 水平;p=0.004)。这与从多柔比星脂质体给药开始的无进展生存期和总生存期的改善有关。值得注意的是,铂类药物敏感性与多柔比星脂质体的反应并不直接相关。
与未选择的病例相比,携带 BRCA 相关卵巢肿瘤的女性对多柔比星脂质体的细胞毒性治疗更敏感。