A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study).
A phase I study of irinotecan and pegylated liposomal doxorubicin in recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 104 study).
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DOI：
10.1007/s00280-014-2418-8
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发表时间：
2014-05
影响因子：
3
通讯作者：
Sugiyama, Toru
中科院分区：
文献类型：
--
作者：
Shoji, Tadahiro;Takatori, Eriko;Kaido, Yoshitaka;Omi, Hideo;Yokoyama, Yoshihito;Mizunuma, Hideki;Kaiho, Michiko;Otsuki, Takeo;Takano, Tadao;Yaegashi, Nobuo;Nishiyama, Hiroshi;Fujimori, Keiya;Sugiyama, Toru
进行了一项I期临床研究，以确定盐酸伊立替康（CPT-11）在CPT-11/聚乙二醇化脂质体多柔比星（PLD）联合治疗中的最大耐受剂量（MTD）和推荐剂量（RD），这是一种铂类和紫杉烷类耐药复发性卵巢癌的新型治疗方案。在第3天以30 mg/m2的固定剂量静脉内施用聚乙二醇化脂质体阿霉素。CPT-11在第1天和第15天以50 mg/m2的剂量静脉给药。一个化疗疗程为28天，患者最多接受6个疗程，CPT-11剂量以10 mg/m2的增量增加（水平1，50 mg/m2;水平2，60 mg/m2;水平3，70 mg/m2;水平4，80 mg/m2），以确定MTD和RD。2010年4月至2013年3月期间，每个节段入组3例患者。在第一个疗程中，任何患者均未发生剂量限制性毒性。在4级的3例患者中，有2例观察到4级中性粒细胞减少。在4级，3例患者中有2例的抗肿瘤效应为部分缓解（PR），1例为疾病稳定（SD）。在3级，3例患者中有1例显示PR，2例显示SD。在第4级，三名患者中有两名推迟了下一个疗程的开始。此外，1例4级患者发生血液毒性，符合下一疗程剂量降低标准。上述结果表明，CPT-11以剂量水平5（90 mg/m2）给药将导致更多患者出现重度中性粒细胞减少，更多患者需要推迟下一疗程或降低剂量。基于上述情况，确定CPT-11的RD为80 mg/m2。结果表明，CPT-11/PLD联合治疗复发性卵巢癌是一种有效的治疗方法，有效率高，不良反应可控。在未来的II期研究中，将评估CPT-11 80 mg/m2和PLD 30 mg/m2的安全性和有效性。
A phase I clinical study was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan hydrochloride (CPT-11) in CPT-11/pegylated liposomal doxorubicin (PLD) combination therapy, a novel treatment regimen for platinum- and taxane-resistant recurrent ovarian cancer. Pegylated liposomal doxorubicin was administered intravenously on day 3 at a fixed dose of 30 mg/m2. CPT-11 was administered intravenously on days 1 and 15, at a dose of 50 mg/m2 on both days. One course of chemotherapy was 28 days, and patients were given a maximum of six courses, with the CPT-11 dose being increased in increments of 10 mg/m2 (level 1, 50 mg/m2; level 2, 60 mg/m2; level 3, 70 mg/m2; level 4, 80 mg/m2) to determine MTD and RD. During the period from April 2010 to March 2013, three patients were enrolled for each level. In the first course, no dose-limiting toxicity occurred in any of the patients. Grade 4 neutropenia was observed in two of three patients at level 4. At level 4, the antitumor effect was a partial response (PR) in two of the three patients and stable disease (SD) in one. At level 3, one of the three patients showed PR and two had SD. At level 4, the start of the next course was postponed in two of three patients. In addition, one patient at level 4 experienced hemotoxicity that met the criteria for dose reduction in the next course. The above results suggested that administration of CPT-11 at dose level 5 (90 mg/m2) would result in more patients with severe neutropenia and in more patients requiring postponement of the next course or a dose reduction. Based on the above, the RD of CPT-11 was determined to be 80 mg/m2. The results suggest that CPT-11/PLD combination therapy for recurrent ovarian cancer is a useful treatment method with a high response rate and manageable adverse reactions. In the future phase II study, the safety and efficacy of this therapy will be assessed at 80 mg/m2 of CPT-11 and 30 mg/m2 of PLD.
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影响因子：
45.3
作者：
Ferrandina, Gabriella;Ludovisi, Manuela;Scambia, Giovanni
通讯作者：
Scambia, Giovanni
影响因子：
10.3
作者：
du Bois, A;Lück, HJ;Pfisterer, J
通讯作者：
Pfisterer, J
影响因子：
2.4
作者：
Aoki, Daisuke;Katsumata, Noriyuki;Noda, Kiichiro
通讯作者：
Noda, Kiichiro
影响因子：
4.7
作者：
Nishio, Shin;Sugiyama, Toru;Kamura, Toshiharu
通讯作者：
Kamura, Toshiharu
影响因子：
4.7
作者：
Matsumoto, K;Katsumata, N;Fujiwara, Y
通讯作者：
Fujiwara, Y