A phase I trial of combination therapy using gemcitabine and S-1 concurrent with full-dose radiation for resectable pancreatic cancer

作者：Eguchi Hidetoshi^*; Nagano Hiroaki; Kobayashi Shogo; Kawamoto Koichi; Wada Hiroshi; Hama Naoki; Tomimaru Yoshito; Akita Hirofumi; Sakai Daisuke; Satoh Taroh; Kudo Toshihiro; Isohashi Fumiaki; Mori Masaki; Doki Yuichiro

来源：Cancer Chemotherapy and Pharmacology, 2014, 73(2): 309-315.

DOI：10.1007/s00280-013-2357-9

• Pancreatic ductal adenocarcinoma
• Neoadjuvant chemotherapy
• Gemcitabine
• S-1
• Chemoradiotherapy

Use of the fourth-generation oral fluoropyrimidine S-1 together with gemcitabine has shown striking anticancer effects. In this single-arm phase I trial of preoperative combination therapy using gemcitabine and S-1 concurrently with radiotherapy, we verified the safety and feasibility and determined the maximum-tolerated dose of each drug in patients with resectable pancreatic cancer.
A standard 3+3 dose escalation scheme was used. Patients with cytologically or histologically proven resectable pancreatic ductal adenocarcinoma were administered 30-min intravenous gemcitabine infusions on days 1, 8, 22, and 29 and S-1 orally on days 1-5, 8-12, 22-26, and 29-33. A total radiation dose of 50.4 Gy (1.8 Gy/day, 5 times per week, 28 fractions) was concurrently delivered. Surgical exploration was scheduled 4-7 weeks after the final radiation fraction.
Twenty-one patients were enrolled. No treatment-related deaths occurred during this study. Recommended doses were determined to be 80 mg/m(2) of S-1 daily and 1,000 mg/m(2) of gemcitabine. CA19-9 was reduced to < 50 % of baseline values in 12 (75 %) of 16 measurable patients. Nineteen of 21 enrolled patients successfully underwent surgical resection.
Preoperative chemoradiotherapy consisting of gemcitabine and S-1 concurrent with full-dose radiation is feasible and well tolerated.

• 出版日期2014-2