吉西他滨、顺铂和S-1联合化疗用于晚期胆管癌患者的I期试验。
Phase I trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer.
作者信息
Watanabe Akinori, Kida Mitsuhiro, Miyazawa Shiro, Iwai Tomohisa, Okuwaki Kosuke, Kaneko Toru, Yamauchi Hiroshi, Takezawa Miyoko, Imaizumi Hiroshi, Koizumi Wasaburo
机构信息
Akinori Watanabe, Mitsuhiro Kida, Shiro Miyazawa, Tomohisa Iwai, Kosuke Okuwaki, Toru Kaneko, Hiroshi Yamauchi, Miyoko Takezawa, Hiroshi Imaizumi, Wasaburo Koizumi, Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara City, Kanagawa 252-0374, Japan.
出版信息
World J Gastroenterol. 2015 May 21;21(19):5979-84. doi: 10.3748/wjg.v21.i19.5979.
AIM
To evaluate the dose-limiting toxicities (DLTs) and determine the maximum-tolerated dose (MTD) and recommended dose (RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.
METHODS
Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine (mg/m(2)), cisplatin (mg/m(2)), and S-1 (mg/m(2) per day) were as follows: level -1, 800/20/60; level 0, 800/25/60; level 1, 1000/25/60; and level 2, 1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15, and S-1 was administered orally twice daily on days 1 to 7 and days 15 to 21, every 4 wk.
RESULTS
Twelve patients were enrolled, and level 0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs (grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1. We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase II study.
CONCLUSION
The RD was defined as gemcitabine 1000 mg/m(2) (days 1, 15), cisplatin 25 mg/m(2) (days 1, 15), and S-1 80 mg/m(2) per day (days 1-7, 15-21), every 4 weeks. A phase II study is planned to evaluate the effectiveness of combination chemotherapy with gemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.
目的
评估吉西他滨、顺铂与口服氟嘧啶前体药物S-1联合化疗在晚期胆管癌患者中的剂量限制性毒性（DLT），确定最大耐受剂量（MTD）和推荐剂量（RD）。
方法
纳入经组织学或细胞学确诊为不可切除或复发性胆管癌的患者。吉西他滨（mg/m²）、顺铂（mg/m²）和S-1（mg/m²/天）的计划剂量水平如下：-1级，800/20/60；0级，800/25/60；1级，1000/25/60；2级，1000/25/80。在每个周期中，吉西他滨和顺铂于第1天和第15天静脉给药，S-1于第1至7天和第15至21天每天口服两次，每4周重复一次。
结果
共纳入12例患者，选择0级作为起始剂量。前三例患者在0级剂量时均未出现DLT，剂量升至1级。6例患者中有1例在1级剂量时出现DLT（4级发热性中性粒细胞减少、白细胞减少和中性粒细胞减少；3级血小板减少）。然后进入2级剂量。3例患者在第一个周期中均未出现DLT。虽然未确定MTD，但2级被指定为后续II期研究的RD。
结论
RD定义为吉西他滨1000 mg/m²（第1、15天）、顺铂25 mg/m²（第1、15天）和S-1 80 mg/m²/天（第1至7天、15至21天），每4周一次。计划进行一项II期研究，以评估吉西他滨、顺铂和S-1联合化疗在晚期胆管癌中的疗效。
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