Sato Yasuhiro, Kondo Hitoshi, Honda Kana, Takahari Daisuke, Sumiyoshi Tetsuya, Tsuji Yasushi, Yoshizaki Naohito, Niitsu Yoshiro
Gastroenterology Center, Tonan Hospital, Sapporo, Japan.
Int J Clin Oncol. 2005 Feb;10(1):40-4. doi: 10.1007/s10147-004-0451-z.
The combination of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active chemotherapy regimens for gastric cancer. However, the optimum schedule for this combination has not yet been determined. This study was conducted to establish the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined with 2-week S-1 administration, and to observe the safety and efficacy of the regimen as treatment for patients with advanced gastric cancer.
S-1 was administered orally at a dose of 80 mg/m2 per day for 2 weeks, followed by a 2-week rest. CDDP was administered intravenously on day 8 of each course; the initial dose of CDDP was 60 mg/m2 and it was increased in 10-mg/m2 increments. Treatment was repeated every 4 weeks unless disease progression was observed.
Eleven patients were enrolled. The main toxicities were leucopenia, neutropenia, nausea, and anorexia. These toxicities were not severe, and were reversible and manageable. The MTD for CDDP was established as 80 mg/m2, as 2 of 5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore, the recommended dose of CDDP was determined to be 70 mg/m2. All 11 patients were evaluable for a response: 8 achieved a partial response and 1 had stable disease. The overall response rate was 73%.
This regimen is considered to be generally well-tolerated and has substantial antitumor activity.
新型口服二氢嘧啶脱氢酶抑制性氟嘧啶（S-1）与顺铂（CDDP）联合使用是治疗胃癌最有效的化疗方案之一。然而，这种联合用药的最佳方案尚未确定。本研究旨在确定与2周S-1给药联合使用时CDDP的最大耐受剂量（MTD）和推荐剂量，并观察该方案作为晚期胃癌患者治疗方法的安全性和有效性。
S-1以每日80mg/m²的剂量口服给药2周，随后休息2周。CDDP在每个疗程的第8天静脉给药；CDDP的初始剂量为60mg/m²，并以10mg/m²的增量增加。除非观察到疾病进展，否则每4周重复治疗一次。
共纳入11例患者。主要毒性反应为白细胞减少、中性粒细胞减少、恶心和厌食。这些毒性反应并不严重，且是可逆的和可控制的。CDDP的MTD确定为80mg/m²，因为5例患者中有2例（40%）在此剂量水平出现剂量限制性毒性（DLT）。因此，CDDP的推荐剂量确定为70mg/m²。所有11例患者均可评估疗效：8例达到部分缓解，1例病情稳定。总缓解率为73%。
该方案被认为总体耐受性良好，具有显著的抗肿瘤活性。
