Phase I/II study of the pharmacokinetics, safety and efficacy of S-1 in patients with advanced hepatocellular carcinoma
Phase I/II study of the pharmacokinetics, safety and efficacy of S-1 in patients with advanced hepatocellular carcinoma
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DOI：
10.1111/j.1349-7006.2010.01730.x
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发表时间：
2010-12-01
期刊：
影响因子：
5.7
通讯作者：
Ueshima, Kazuomi
中科院分区：
文献类型：
--
作者：
Furuse, Junji;Okusaka, Takuji;Ueshima, Kazuomi
S-1是一种口服氟嘧啶衍生物，已被证明在临床上对各种实体瘤有效，临床前研究已证明对肝细胞癌有活性。我们在晚期肝癌患者中进行了一项I/II期研究，以检查S-1的药代动力学、推荐剂量、安全性和有效性。在I期试验中，3名患者的S-1给药剂量约为每天64mg /m2（一级），6名患者的S-1给药剂量约为每天80mg /m2（二级）。1级没有剂量限制性毒性，但2例患者出现剂量限制性毒性（3级厌食症和2级皮疹，需要连续休息8天或更长时间）。最终估计推荐剂量为每天80 mg/m2。Child-Pugh A和b患者的S-1药代动力学无显著差异。在II期，23例患者中有5例（21.7%）部分缓解。中位无进展生存期和总生存期分别为3.7和16.6个月。3级或4级最常见的毒性是血清天冬氨酸转氨酶水平升高、低色素血症和血小板减少症。总之，S-1显示出可接受的毒性特征和有希望的抗肝癌活性，值得在随机临床试验中进一步评估。[j] .癌症科学，2010;01:2606-2611。
S-1, an oral fluoropyrimidine derivative, has been shown to be clinically effective against various solid tumors, and preclinical studies have demonstrated activity against hepatocellular carcinoma. We conducted a phase I/II study in patients with advanced hepatocellular carcinoma to examine the pharmacokinetics, recommended dose, safety and efficacy of S-1. In phase I, the administered dose of S-1 was approximately 64 mg/m2 per day in three patients (level 1) and approximately 80 mg/m2 per day in six patients (level 2). There was no dose-limiting toxicity at level 1, but two patients had dose-limiting toxicity at level 2 (grade 3 anorexia and grade 2 rash requiring eight or more consecutive days of rest). The recommended dose was finally estimated to be 80 mg/m2 per day. There were no significant differences in the pharmacokinetics of S-1 between patients with Child-Pugh A and those with B. In phase II, five of 23 patients (21.7%) had partial responses. The median progression-free survival and overall survival were 3.7 and 16.6 months, respectively. The most common toxicities of grade 3 or 4 were elevated serum aspartate aminotransferase levels, hypochromia and thrombocytopenia. In conclusion, S-1 showed an acceptable toxicity profile and promising antitumor activity for hepatocellular carcinoma, warranting further evaluation in randomized clinical trials. (Cancer Sci 2010; 101: 2606-2611).