Phase I study of neoadjuvant chemoradiotherapy with S-1 plus biweekly cisplatin for advanced gastric cancer patients with lymph node metastasis:-KOGC04-

被引:13
作者
Matsuda, Satoru [1 ]
Takahashi, Tsunehiro [1 ]
Fukada, Junichi [2 ]
Fukuda, Kazumasa [1 ]
Kawakubo, Hirofumi [1 ]
Saikawa, Yoshiro [1 ]
Kawaguchi, Osamu [2 ]
Takeuchi, Hiroya [1 ]
Shigematsu, Naoyuki [2 ]
Kitagawa, Yuko [1 ]
机构
[1] Keio Univ, Sch Med, Dept Surg, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Radiol, Shinjuku Ku, Tokyo 1608582, Japan
关键词
Gastric cancer; Neoadjuvant; Chemoradiotherapy; S-1; Cisplatin; Phase I; III TRIAL; ADJUVANT CHEMOTHERAPY; SURGERY; FEASIBILITY; DISSECTION; RECURRENCE;
D O I
10.1186/1748-717X-9-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin. Methods: Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1-15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m(2), the second dose (level 2) was 20 mg/m(2), and the third dose (level 3) was 25 mg/m(2). Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1-29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned. Results: Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m(2)) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m(2)) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response. Conclusions: In this phase I trial, RD of cisplatin was identified as 20 mg/m(2). Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach.
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