口服S-1联合吉西他滨肝动脉灌注治疗不可切除胆管癌的I期试验
Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer.
作者信息
Ishiwatari Hirotoshi, Hayashi Tsuyoshi, Yoshida Makoto, Ono Michihiro, Sato Tsutomu, Miyanishi Koji, Sato Yasushi, Takimoto Rishu, Kobune Masayoshi, Kato Junji
机构信息
Department of Medical Oncology and Hematology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, 060-8543, Japan,
出版信息
Cancer Chemother Pharmacol. 2015 Apr;75(4):805-12. doi: 10.1007/s00280-015-2704-0. Epub 2015 Feb 17.
PURPOSE
S-1 and gemcitabine (GS) combination therapy is a promising treatment for advanced biliary tract cancer (BTC). However, systemic administration of GS is associated with a high rate of grade 3 and 4 neutropenia. Hepatic arterial infusion (HAI) of gemcitabine may overcome this problem. We conducted a prospective phase 1 trial to determine the maximum tolerated dose (MTD) of S-1 and rates of dose-limiting toxicities (DLTs) associated with HAI of gemcitabine in patients with unresectable BTC.
METHODS
BTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m(2) on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m(2) on days 1-14) until disease progression occurred.
RESULTS
Fifteen patients were enrolled in the study. Grade 3 and 4 neutropenia occurred in five of 15 (33%) patients. Among six patients who were treated with 60 mg/m(2) S-1, one developed grade 4 neutropenia. DLTs (grade 4 neutropenia and bladder infection) occurred in two of six patients who were treated with 70 mg/m(2) S-1. Two of the three patients who were treated with 80 mg/m(2) S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m(2) was defined as the MTD of S-1.
CONCLUSION
The MTD of oral S-1 in GS therapy is 80 mg/m(2). Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.
目的
S-1与吉西他滨（GS）联合疗法是晚期胆管癌（BTC）一种有前景的治疗方法。然而，全身性给予GS与3级和4级中性粒细胞减少的高发生率相关。吉西他滨肝动脉灌注（HAI）可能克服这一问题。我们开展了一项前瞻性1期试验，以确定不可切除BTC患者中S-1的最大耐受剂量（MTD）以及与吉西他滨HAI相关的剂量限制性毒性（DLT）发生率。
方法
BTC患者接受吉西他滨HAI（第1天和第8天为1000mg/m²）和口服S-1（第1 - 14天为60、70或80mg/m²）的21天周期治疗，直至疾病进展。
结果
15例患者入组本研究。15例患者中有5例（33%）发生3级和4级中性粒细胞减少。在接受60mg/m² S-1治疗的6例患者中，1例发生4级中性粒细胞减少。在接受70mg/m² S-1治疗的6例患者中，2例发生DLT（4级中性粒细胞减少和膀胱感染）。在接受80mg/m² S-1治疗的3例患者中，2例出现DLT（4级白细胞减少和中性粒细胞减少以及3级发热性中性粒细胞减少）。因此，80mg/m²被定义为S-1的MTD。
结论
GS治疗中口服S-1的MTD为80mg/m²。此外，吉西他滨HAI可能降低接受GS治疗的BTC患者中3级和4级中性粒细胞减少的发生率。
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