Phase II trial with S-1 in chemotherapy-naive patients with gastric cancer.: A trial performed by the EORTC Early Clinical Studies Group (ECSG)
Phase II trial with S-1 in chemotherapy-naive patients with gastric cancer.: A trial performed by the EORTC Early Clinical Studies Group (ECSG)
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DOI：
10.1016/s0959-8049(03)00237-5
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发表时间：
2003-06-01
影响因子：
8.4
通讯作者：
Fumoleau, P
中科院分区：
文献类型：
--
作者：
Chollet, P;Schöffski, P;Fumoleau, P
S-1是一种新的口服氟嘧啶衍生物，其中口服5-氟尿嘧啶（5-FU）前药替加氟与两种5-FU调节物质5-氯-2，4-二羟基吡啶（吉美拉西）和氧嗪酸钾（奥替拉西）以1：0.4：1的摩尔比组合。最终的作用机制是由5-FU发挥作用。本研究是欧洲第一个S-I治疗胃癌的11期临床试验。主要研究目的是S-I在未经预治疗的胃癌患者中的安全性、毒性和活性。次要目的是缓解持续时间。患者必须患有组织学或细胞学证实的转移性或局部晚期不可切除的胃癌; S-I口服给药，每天两次，剂量为40 mg/m2，然后是35 mg/m2，每5周给药28天。由于显著的非血液学毒性，发现40 mg/m2的起始剂量不可耐受，该剂量迅速降至35 mg/m2，每日两次。在40 mg/m2水平入组的7例患者中，仅3例可评价。在35 mg/m2剂量下，23例入组患者的缓解率为26.1%（95%置信区间（CI）12.0-45.1%），31.6%（CI 12.0-45.1%）。35 mg/m2（6例患者）的中位反应持续时间为223天（范围108-828天），稳定期为111天（范围68-411天）。在欧洲患者中，S-I的给药剂量为35 mg/m2，第1-28天，每5周一次，安全性和毒性均可接受，并且与其他氟嘧啶类药物获得的结果相似，具有中等缓解率。(C)2003爱思唯尔科技有限公司版权所有。
S-1 is a new oral fluorinated pyrimidine derivate, in which the oral 5-fluorouracil (5-FU) prodrug, tegafur, was combined with two 5-FU-modulating substances, 5-chloro-2,4-dihydroxypyridine (gimeracil), and potassium oxonate (oteracil), at a molar ratio of 1:0.4:1. The final mechanism of action is exerted by 5-FU. The present study is the first European phase 11 trial of S-I in gastric cancer. The primary study objectives were the safety, toxicity and activity of S-I in non-pretreated patients with gastric cancer. The secondary objective was the duration of response. Patients had to have histologically- or cytologically-verified metastatic or locally advanced, unresectable gastric cancer; S-I was administered orally twice daily at 40, then 35 mg/m(2) for 28 days every 5 weeks. The starting dose of,40 mg/m(2) was found to be intolerable due to significant non-haematological toxicity, and this dose was rapidly reduced to 35 mg/m(2) twice daily. Of the 7 patients enrolled at the 40 mg/m(2) level, only 3 were evaluable. At 35 mg/m(2), a response rate of 26.1% (95% Confidence Interval (CI) 12.0-45.1%) in 23 enrolled patients, and 31.6% (C.I. 14.7-53.0%) in 19 evaluable patients according to an independent radiology review, was found. The median duration of response at 35 mg/m(2) (6 patients) was 223 days (range, 108-828 days), and of stable disease was I I I days (range 68-411 days). S-I can be administered with an acceptable safety and toxicity in European patients at a dose of 35 mg/m(2) days 1-28 every 5 weeks and is associated with a moderate response rate similar to the results achieved with other fluoropyrimidines. (C) 2003 Elsevier Science Ltd. All rights reserved.