title: A phase I-II study of postoperative capecitabine-based chemoradiotherapy in gastric cancer.
abstract: BACKGROUND
  The Intergroup 0116 randomized study showed that postoperative 5-fluorouracil-based chemoradiotherapy improved locoregional control and overall survival in patients with gastric cancer. We hypothesized that these results could be improved further by using a more effective, intensified, and convenient chemotherapy schedule. Therefore, this Phase I-II dose-escalation study was performed to determine the maximal tolerated dose and toxicity profile of postoperative radiotherapy combined with concurrent capecitabine.
  
  
  METHODS
  After recovery from surgery for adenocarcinoma of the gastroesophageal junction or stomach, all patients were treated with capecitabine monotherapy, 1,000 mg/m2 twice daily for 2 weeks. After a 1-week treatment-free interval, patients received capecitabine (650-1,000 mg/m2 orally twice daily 5 days/week) in a dose-escalation schedule combined with radiotherapy on weekdays for 5 weeks. Radiotherapy was delivered to a total dose of 45 Gy in 25 fractions to the gastric bed, anastomoses, and regional lymph nodes.
  
  
  RESULTS
  Sixty-six patients were treated accordingly. Two patients went off study before or shortly after the start of chemoradiotherapy because of progressive disease. Therefore, 64 patients completed treatment as planned. During the chemoradiotherapy phase, 4 patients developed four items of Grade III dose-limiting toxicity (3 patients in Dose Level II and 1 patient in Dose Level IV). The predefined highest dose of capecitabine, 1,000 mg/m2 twice daily orally, was tolerated well and, therefore, considered safe for further clinical evaluation.
  
  
  CONCLUSIONS
  This Phase I-II study shows that intensified chemoradiotherapy with daily capecitabine is feasible in postoperative patients with gastroesophageal junction and gastric cancer.
authors: Department of Radiotherapy of The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. epm.jansen@nki.nl
authors: Edwin P M
authors: EP
authors: Jansen
authors: Henk
authors: H
authors: Boot
authors: Mark P
authors: MP
authors: Saunders
authors: Tom D L
authors: TD
authors: Crosby
authors: Ria
authors: R
authors: Dubbelman
authors: Harry
authors: H
authors: Bartelink
authors: Marcel
authors: M
authors: Verheij
authors: Annemieke
authors: A
authors: Cats
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000069287:Capecitabine; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004943:Esophagogastric Junction; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011879:Radiotherapy Dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil