title: Phase I study of postoperative radiotherapy combined with capecitabine for gastric cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of capecitabine combined with postoperative radiotherapy for gastric cancer.
  
  
  METHODS
  We enrolled patients with any T stage and node-positive gastroesophageal or gastric adenocarcinoma after complete resection with negative margins (R0) or microscopic (R1) or macroscopic (R2) resection. Intensity modulated radiotherapy (IMRT) using a five-to-seven-field, coplanar, sliding window technique was delivered to the tumor bed (T4b), anastomosis site, duodenal stump and regional lymph nodes (LNs) to a total dose of 45 Gy (1.8 Gy/fraction, 5 d/wk). Patients with R1 or R2 resection received 10.8 Gy as a boost. Capecitabine was administered twice daily on every radiotherapy treatment day in a dose-escalation schedule (mg/m²) of 625 (level I, n = 6), 700 (level II, n = 6), 800 (level III, n = 6), 900 (level IV, n = 0) and 1000 (level V, n = 0). DLT was defined as grade 4 leukopenia or neutropenia, grade 3-4 thrombocytopenia or anemia and grade 3-4 non-hematological toxicity.
  
  
  RESULTS
  Between October 2007 and August 2009, 18 patients (12 men, 6 women; median age, 54 years) were enrolled in the study. The median number of positive LNs was 6, and total number of resected LNs was 19. Twelve patients underwent R0 resection (66.7%). Fifteen patients received adjuvant chemotherapy under the leucovorin, fluorouracil and oxaliplatin (FOLFOX4) regimen. Six patients each were enrolled at dose levels I, II and III. Grade 1-3 leukopenia (16 patients, 88.9%), anorexia (15, 83.3%) and nausea (15, 83.3%) were the most common toxicities. Grade 3 anorexia/nausea and grade 4 vomiting occurred in one level-I patient. Grade 3 anorexia and nausea occurred in one level-II patient. One level-III patient developed grade 4 neutropenia, while another developed grade 3 radiation esophagitis. No abnormal liver or renal function examinations were observed. Three patients did not finish chemoradiotherapy because of DLTs and two without DLTs received sequential boosts (total dose, 55.8 Gy).
  
  
  CONCLUSIONS
  The MTD of capecitabine was 800 mg/m² twice daily concurrent with IMRT for gastric cancer after surgery. The DLTs were anorexia/nausea, vomiting, neutropenia and radiation esophagitis.
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Ye-Xiong
authors.initials: YX
authors.lastname: Li
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Ren
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Shu-Lian
authors.initials: SL
authors.lastname: Wang
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Wei-Hu
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Zi-Hao
authors.initials: ZH
authors.lastname: Yu
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Yong-Wen
authors.initials: YW
authors.lastname: Song
authors.affiliation: Xin Wang, Jing Jin, Ye-Xiong Li, Hua Ren, Hui Fang, Shu-Lian Wang, Yue-Ping Liu, Wei-Hu Wang, Zi-Hao Yu, Yong-Wen Song, Xin-Fan Liu, Department of Radiation Oncology, Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Xin-Fan
authors.initials: XF
authors.lastname: Liu
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000401:mortality; D002681:China; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005743:Gastrectomy / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil
keywords: Capecitabine; Dose-limiting toxicity; Gastric cancer; Maximum tolerated dose; Radiotherapy