Shoji Tadahiro, Takatori Eriko, Omi Hideo, Kagabu Masahiro, Honda Tatsuya, Futagami Masayuki, Yokoyama Yoshihito, Kaiho Michiko, Tokunaga Hideki, Otsuki Takeo, Takano Tadao, Yaegashi Nobuo, Kojimahara Takanobu, Ohta Tsuyoshi, Nagase Satoru, Soeda Shu, Watanebe Takafumi, Nishiyama Hiroshi, Sugiyama Toru
Department of Obstetrics and Gynecology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan.
Department of Obstetrics and Gynecology, Morioka Japanese Red Cross Hospital, 6-1-1 Sanbonyanagi, Morioka, 020-8560, Japan.
Cancer Chemother Pharmacol. 2017 Aug;80(2):355-361. doi: 10.1007/s00280-017-3363-0. Epub 2017 Jun 27.
We report a phase II clinical study of the combination of irinotecan (CPT-11) and pegylated liposomal doxorubicin (PLD) in platinum- and taxane-resistant recurrent ovarian cancer, based on the recommended doses determined in a phase I trial.
PLD was administered intravenously at a dose of 30 mg/m on day 3. CPT-11 was administered intravenously at a dose of 80 mg/m on days 1 and 15, according to the recommendations of the phase I study. A single course of chemotherapy lasted 28 days, and patients underwent at least 2 courses until disease progression. The primary endpoint was antitumor efficacy, and the secondary endpoints were adverse events, progression-free survival (PFS), and overall survival (OS).
The response rate was 32.3% and the disease control rate was 64.5%. Grade 3 and 4 neutropenia, anemia, and a decrease in platelet count were observed in 17 (54.9%), 3 (9.7%), and 1 patient (3.2%), respectively. In terms of grade 3 or higher non-hematologic toxicities, grade 3 nausea occurred in 1 patient (3.2%), vomiting in 3 patients (9.7%), and grade 3 diarrhea and fatigue in 1 patient (3.2%). The median PFS and OS rates were 2 months and not reached, respectively. Of the 11 patients with a treatment-free interval (TFI) of ≥3 months, the response rate was 63.3%, and the median PFS was 7 months.
The treatment outcomes for the 31 patients enrolled in this study were unsatisfactory. However, sub-analysis suggested that patients with a TFI of ≥3 months had a good response rate and PFS. This suggests that CPT-11/PLD combination therapy may be a chemotherapy option for platinum-resistant recurrent ovarian cancer.
基于在I期试验中确定的推荐剂量，我们报告了伊立替康（CPT-11）与聚乙二醇化脂质体阿霉素（PLD）联合用于铂类和紫杉烷耐药的复发性卵巢癌的II期临床研究。
第3天静脉注射PLD，剂量为30mg/m²。根据I期研究的建议，第1天和第15天静脉注射CPT-11，剂量为80mg/m²。一个化疗疗程持续28天，患者接受至少2个疗程直至疾病进展。主要终点是抗肿瘤疗效，次要终点是不良事件、无进展生存期（PFS）和总生存期（OS）。
缓解率为32.3%，疾病控制率为64.5%。分别有17例（54.9%）、3例（9.7%）和1例（3.2%）患者出现3级和4级中性粒细胞减少、贫血以及血小板计数下降。在3级或更高等级的非血液学毒性方面，1例患者（3.2%）出现3级恶心，3例患者（9.7%）出现呕吐，1例患者（3.2%）出现3级腹泻和疲劳。中位PFS和OS率分别为2个月和未达到。在11例无治疗间隔（TFI）≥3个月的患者中，缓解率为63.3%，中位PFS为7个月。
本研究纳入的31例患者的治疗结果并不理想。然而，亚组分析表明，TFI≥3个月的患者缓解率和PFS良好。这表明CPT-11/PLD联合治疗可能是铂耐药复发性卵巢癌的一种化疗选择。
