title: Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma.
abstract: BACKGROUND
  Based on the observation of topoisomerase-1, upregulation by mitomycin C (MMC), and the phase I antitumor activity of sequential MMC/irinotecan in esophageal cancer, we conducted a phase II evaluation of two schedules of this combination in previously untreated stage III/IV esophageal/gastroesophageal junction adenocarcinomas.
  
  
  METHODS
  Patients (n = 76) were randomized to either 6 mg/m MMC on day 1 and 125 mg/m irinotecan on days 2 and 9 (arm A) or 3 mg/m MMC on days 1 and 8 and 125 mg/m irinotecan on days 2 and 9 (arm B). Each cycle was repeated every 28 days. Restaging was planned after two cycles, and resections were performed whenever possible. A two-stage Simon minimax design was used for each arm, with a "pick-the-winner" approach based on efficacy.
  
  
  RESULTS
  The response rate (complete response + partial response) in 73 evaluable patients was 52% (21 of 40 patients) for arm A and 33% (11/33) for arm B. Moderate or severe toxicity was similar. Twenty-seven patients were resected (20:7, arm A:B). There was one complete pathologic response; five others were node negative.
  
  
  CONCLUSIONS
  Irinotecan/MMC is feasible in esophageal/gastroesophageal junction adenocarcinoma. MMC (6 mg/m) every 28 days for up to six cycles is the recommended modulatory dose for irinotecan in future trials.
authors.affiliation: Department of Internal Medicine, Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210-1240, USA.
authors.forename: Maryam B
authors.initials: MB
authors.lastname: Lustberg
authors.forename: Tanios
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: Donn
authors.initials: D
authors.lastname: Young
authors.forename: Gregory
authors.initials: G
authors.lastname: Otterson
authors.forename: William
authors.initials: W
authors.lastname: Burak
authors.forename: Abbas
authors.initials: A
authors.lastname: Abbas
authors.forename: Barbara
authors.initials: B
authors.lastname: McCracken-Bussa
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lustberg
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Villalona-Calero
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004943:Esophagogastric Junction / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016685:Mitomycin; D000077146:Irinotecan; D002166:Camptothecin