Hosokawa Ayumu, Ando Takayuki, Ogawa Kohei, Ueda Akira, Yoshita Hiroki, Mihara Hiroshi, Fujinami Haruka, Kajiura Shinya, Yabushita Kazuhisa, Horikawa Naoki, Kobayashi Yuka, Yoshioka Akira, Origasa Hideki, Sugiyama Toshiro
Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama.
Department of Surgery, Takaoka City Hospital, Takaoka.
Am J Clin Oncol. 2018 Oct;41(10):977-981. doi: 10.1097/COC.0000000000000405.
To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with advanced gastric cancer, we conducted a phase I/II study to determine the maximum tolerated dose and recommended dose, and evaluate efficacy and toxicity.
Patients with histologically confirmed unresectable and recurrent gastric cancer were enrolled in this study. Cisplatin was administered on day 1 and the dose escalated by 10 mg/m from a starting dose of 40 mg/m in the phase I part. S-1 was given orally at 80 mg/m on days 1 to 14 and docetaxel at 40 mg/m on day 22 in combination with S-1 80 mg/m on days 22 to 35. The treatment was repeated every 6 weeks. The primary endpoint of the phase II analysis was the response rate.
Nine patients entered the phase I and 24 the phase II part. Because 50% of patients (3/6) developed dose-limiting toxicities in the phase I part, the maximum tolerated dose of cisplatin was presumed to be 50 mg/m. Therefore, the estimated recommended dose of cisplatin was 40 mg/m; 27 patients received that dose. The response rate was 59.3% (95% confidence interval, 40.8-77.8) and the median follow-up 26.2 months. The median progression-free survival was 7.9 months and the median overall survival 18.6 months. The most common grade 3/4 toxicities were neutropenia (59.3%), leucopenia (37.0%), and anemia (29.6%). These toxicities were tolerable and manageable.
This alternating treatment seems to have promising activity with tolerable toxicities in the first-line treatment of patients with advanced gastric cancer.
为了研究S-1联合顺铂与S-1联合多西他赛交替作为晚期胃癌患者一线治疗方案的有效性，我们开展了一项I/II期研究，以确定最大耐受剂量和推荐剂量，并评估疗效和毒性。
组织学确诊为不可切除及复发性胃癌的患者纳入本研究。在I期部分，顺铂于第1天给药，起始剂量为40mg/m²，每次剂量递增10mg/m²。S-1于第1至14天口服，剂量为80mg/m²，多西他赛于第22天给药，剂量为40mg/m²，并联合第22至35天口服的S-1，剂量为80mg/m²。每6周重复一次治疗。II期分析的主要终点为缓解率。
9例患者进入I期，24例进入II期。由于I期部分50%的患者（3/6）出现了剂量限制性毒性，因此顺铂的最大耐受剂量推测为50mg/m²。因此，顺铂的估计推荐剂量为40mg/m²；27例患者接受了该剂量。缓解率为59.3%（95%置信区间，40.8 - 77.8），中位随访时间为26.2个月。中位无进展生存期为7.9个月，中位总生存期为18.6个月。最常见的3/4级毒性为中性粒细胞减少（59.3%）、白细胞减少（37.0%）和贫血（29.6%）。这些毒性是可耐受且可管理的。
这种交替治疗方案在晚期胃癌患者的一线治疗中似乎具有良好的活性且毒性可耐受。
