title: Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer.
abstract: Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1 was feasible in gastric cancer and the MTD of S-1 concurrent with radiotherapy was 70 mg/m(2)/day. This S-1-based postoperative CRT will be investigated in a multicenter phase III study in West China.
authors.affiliation: Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy West China Hospital, West China Medical School, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, 610041, Sichuan Province, China, qiumeng33@hotmail.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Qiu
authors.forename: Xing-chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Feng
authors.initials: F
authors.lastname: Bi
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Qiu
authors.initials: Q
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Li
authors.forename: Ya-li
authors.initials: YL
authors.lastname: Shen
authors.forename: Ji-yan
authors.initials: JY
authors.lastname: Liu
authors.forename: Ya-qing
authors.initials: YQ
authors.lastname: Zhao
authors.forename: Dan
authors.initials: D
authors.lastname: Cao
authors.forename: Hong-feng
authors.initials: HF
authors.lastname: Gou
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Yi
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods; D003131:Combined Modality Therapy / Q000379:methods; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin; D010094:Oxonic Acid / Q000627:therapeutic use*; D011182:Postoperative Care / Q000379:methods; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D005641:Tegafur / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005472:Fluorouracil