Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota, 420 Delaware Street SE, MMC 395, Minneapolis, MN 55455, USA.
Int J Clin Oncol. 2011 Dec;16(6):666-70. doi: 10.1007/s10147-011-0243-1. Epub 2011 May 10.
Lenalidomide is an anti-angiogenic IMiD(®) immunomodulatory drug. The objective of this study was to determine the maximum tolerated dose (MTD), overall safety profile, and activity of oral lenalidomide in combination with topotecan in women with advanced epithelial ovarian or primary peritoneal carcinoma.
In this Phase I/II open-label, dose-escalation study, patients with histologically or cytologically confirmed advanced ovarian or primary peritoneal carcinoma with disease progression or recurrence following first-line therapy with a platinum agent and paclitaxel were eligible. The Phase I trial utilized a standard dose-escalation design to define the MTD and evaluate the safety profile of lenalidomide and topotecan. The starting doses were lenalidomide 5 mg, days 1-14, and intravenous topotecan 1.25 mg/m(2), days 1-5 of a 21-day cycle. Only the lenalidomide dose was escalated, in 5-mg increments up to 25 mg. Toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The Phase II portion was designed to evaluate the antitumor activity based on objective response rate of lenalidomide and topotecan.
Five women with advanced epithelial ovarian carcinoma were enrolled, each receiving 5 mg oral lenalidomide and 1.25 mg/m(2) topotecan. Four patients discontinued because of dose-limiting toxicity, most commonly grade 4 neutropenia (n = 3). One patient discontinued because of lack of therapeutic effect. The study was terminated early for reasons of toxicity.
The addition of lenalidomide to topotecan is not a feasible drug combination in women with advanced epithelial ovarian carcinoma because of dose-limiting toxicity.
来那度胺是一种抗血管生成的 IMiD（®）免疫调节药物。本研究的目的是确定最大耐受剂量（MTD）、总体安全性概况以及来那度胺联合拓扑替康在晚期上皮性卵巢癌或原发性腹膜癌女性中的疗效。
这是一项开放标签、剂量递增的 I/II 期研究，纳入的患者为组织学或细胞学证实的晚期卵巢癌或原发性腹膜癌，在接受一线含铂和紫杉醇治疗后疾病进展或复发。I 期试验采用标准剂量递增设计，以确定来那度胺和拓扑替康的 MTD 并评估安全性概况。起始剂量为来那度胺 5mg，每日 1-14 天，静脉注射拓扑替康 1.25mg/m²，每日 1-5 天，每 21 天为一个周期。仅递增来那度胺剂量，每次递增 5mg，最高达 25mg。毒性根据国家癌症研究所不良事件通用术语标准进行分级。II 期部分旨在根据来那度胺和拓扑替康的客观缓解率评估抗肿瘤活性。
共纳入 5 例晚期上皮性卵巢癌患者，每位患者均接受 5mg 口服来那度胺和 1.25mg/m²拓扑替康治疗。4 例患者因剂量限制性毒性（最常见的是 4 级中性粒细胞减少症[n = 3]）而停药。1 例患者因缺乏治疗效果而停药。由于毒性原因，该研究提前终止。
来那度胺联合拓扑替康在晚期上皮性卵巢癌患者中不是一种可行的药物联合方案，因为存在剂量限制性毒性。
