Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer.
Phase I trial of oral S-1 combined with hepatic arterial infusion of gemcitabine in unresectable biliary tract cancer.
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口服 S-1 联合肝动脉灌注吉西他滨治疗不可切除胆道癌的 I 期试验。
DOI：
10.1007/s00280-015-2704-0
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
et al.
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文献类型：
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作者：
Ishiwatari H;Hayashi T;Kato J;et al.
目的S-1联合吉西他滨（GS）治疗晚期胆道癌（BTC）是一种有前途的治疗方法。然而，全身给予GS与3级和4级中性粒细胞减少症的高发生率相关。肝动脉灌注吉西他滨（HAI）可以克服这个问题。我们进行了一项前瞻性1期试验，以确定S-1的最大耐受剂量（MTD）和与吉西他滨HAI相关的剂量限制性毒性（DLT）在不可切除的BTC患者中的发生率。（1000 mg/m2，第1天和第8天）和口服S-1（60、70或80 mg/m2，第1-14天）直至疾病进展。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60 mg/m2 S-1治疗的6例患者中，1例发生4级中性粒细胞减少症。接受70 mg/m2 S-1治疗的6例患者中有2例发生DLT（4级中性粒细胞减少和膀胱感染）。接受80 mg/m2 S-1治疗的3例患者中有2例发生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，S-1的MTD为80 mg/m2。结论口服S-1在GS治疗中的MTD为80 mg/m2。此外，吉西他滨的HAI可降低接受GS治疗的BTC患者中3级和4级中性粒细胞减少的发生率。
PurposeS-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.MethodsBTC patients were treated with 21-day cycles of HAI of gemcitabine (1000 mg/m2on days 1 and 8) and oral S-1 (60, 70, or 80 mg/m2on days 1–14) until disease progression occurred.ResultsFifteen 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/m2S-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/m2S-1. Two of the three patients who were treated with 80 mg/m2S-1 experienced DLTs (grade 4 leukopenia and neutropenia and grade 3 febrile neutropenia). Thus, 80 mg/m2was defined as the MTD of S-1.ConclusionThe MTD of oral S-1 in GS therapy is 80 mg/m2. Furthermore, HAI of gemcitabine may reduce the rate of grade 3 and 4 neutropenia in BTC patients receiving GS therapy.