title: Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin.
abstract: OBJECTIVE
  On initial publication of GI Intergroup Radiation Therapy Oncology Group (RTOG) 98-11 [A Phase III Randomized Study of 5-Fluorouracil (5-FU), Mitomycin, and Radiotherapy Versus 5-Fluorouracil, Cisplatin and Radiotherapy in Carcinoma of the Anal Canal], concurrent chemoradiation (CCR) with fluorouracil (FU) plus mitomycin (MMC) decreased colostomy failure (CF) when compared with induction plus concurrent FU plus cisplatin (CDDP), but did not significantly impact disease-free survival (DFS) or overall survival (OS) for anal canal carcinoma. The intent of the updated analysis was to determine the long-term impact of treatment on survival (DFS, OS, colostomy-free survival [CFS]), CF, and relapse (locoregional failure [LRF], distant metastasis) in this patient group.
  
  
  METHODS
  Stratification factors included sex, clinical node status, and primary size. DFS and OS were estimated univariately by the Kaplan-Meier method, and treatment arms were compared by log-rank test. Time to relapse and CF were estimated by the cumulative incidence method and treatment arms were compared by using Gray's test. Multivariate analyses used Cox proportional hazard models to test for treatment differences after adjusting for stratification factors.
  
  
  RESULTS
  Of 682 patients accrued, 649 were analyzable for outcomes. DFS and OS were statistically better for RT + FU/MMC versus RT + FU/CDDP (5-year DFS, 67.8% v 57.8%; P = .006; 5-year OS, 78.3% v 70.7%; P = .026). There was a trend toward statistical significance for CFS (P = .05), LRF (P = .087), and CF (P = .074). Multivariate analysis was statistically significant for treatment and clinical node status for both DFS and OS, for tumor diameter for DFS, and for sex for OS.
  
  
  CONCLUSIONS
  CCR with FU/MMC has a statistically significant, clinically meaningful impact on DFS and OS versus induction plus concurrent FU/CDDP, and it has borderline significance for CFS, CF, and LRF. Therefore, RT + FU/MMC remains the preferred standard of care.
authors.affiliation: Mayo Clinic Arizona, Scottsdale, AZ 85259, USA. llg.scottsdale@cox.net
authors.forename: Leonard L
authors.initials: LL
authors.lastname: Gunderson
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Winter
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: John E
authors.initials: JE
authors.lastname: Pedersen
authors.forename: Jennifer
authors.initials: J
authors.lastname: Moughan
authors.forename: Al B
authors.initials: AB
authors.lastname: Benson
authors.forename: Charles R
authors.initials: CR
authors.lastname: Thomas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mayer
authors.forename: Michael G
authors.initials: MG
authors.lastname: Haddock
authors.forename: Tyvin A
authors.initials: TA
authors.lastname: Rich
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Willett
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001005:Anus Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003125:Colostomy; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009362:Neoplasm Metastasis; D012008:Recurrence; D016019:Survival Analysis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil