Yamaguchi Kensei, Shimamura Tomotaka, Komatsu Yoshito, Takagane Akinori, Yoshioka Takashi, Saitoh Soh, Munakata Masaki, Sakata Yu, Sato Tsukasa, Arai Tatsuhiro, Saitoh Hiroshi
Department of Gastroenterology, Saitama Cancer Center Hospital, Komuro 818, Ina-machi, Saitama, 362-0806, Japan.
Gastric Cancer. 2006;9(1):36-43. doi: 10.1007/s10120-005-0355-2.
Both paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents.
Nineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m2 dose of CDDP.
In the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18 mg/m2, with CDDP 3 mg/m2, to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16 mg/m2 with CDDP, 3 mg/m2. In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%).
The RD was determined to be TXL 14 mg/m2, with CDDP 3 mg/m2.
紫杉醇（TXL）和顺铂（CDDP）对胃癌均显示出疗效。本I-II期研究的目的是确定最大耐受剂量（MTD），并评估这两种药物联合化疗的毒性和疗效。
19例患者进入研究的I期部分，21例患者进入II期部分。在第1天和第15天给予TXL输注，顺铂剂量固定为3mg/m²。
在研究的I期部分，我们确定5级剂量水平为MTD，即TXL剂量为18mg/m²，顺铂为3mg/m²。推荐剂量（RD）为4级，TXL剂量为16mg/m²，顺铂为3mg/m²。在研究的II期部分，缓解率为25.0%；5例患者部分缓解，7例病情稳定，6例病情进展，2例不可评估。3级或4级中性粒细胞减少是最常见的不良事件，65%的患者发生。治疗期间，25%的患者接受了粒细胞集落刺激因子，但所有患者均未出现发热性中性粒细胞减少。主要的非血液学毒性为恶心/呕吐、厌食、疲劳、脱发和感觉神经病变。2例患者出现3级或4级不良反应，1例为厌食（5%），另1例为感觉神经病变（5%）。
确定的推荐剂量为TXL 14mg/m²，顺铂3mg/m²。
