Intergroup 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

Reviewer: John P. Plastaras, MD, PhD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 7, 2006

Presenter: J.A. Ajani
Presenter's Affiliation: M.D. Anderson Cancer Center, Houston, TX
Type of Session: Scientific


  • The current standard treatment of squamous cell carcinoma of the anus is concurrent chemoradiation (CRT) with 5-FU and mitomycin-C
  • The 5-yr disease free survival (DFS) is ~65%
  • Mitomycin-C has an undesirable side-effect profile, including prolonged thrombocytopenia, renal failure, and hemolytic uremic syndrome
  • The rationale for this study was to use cisplatin (CDDP)-based induction chemotherapy to shrink tumors prior to CRT in hopes of improving locoregional control

Materials and Methods

  • Phase III, multi-center randomized to:
  • Arm A: Standard 5-FU/mito-C concurrent CRT
  • 5-FU (1,000mg/m2 days 1-4 and 29-32) plus mitomycin (10mg/m2 days 1 and 29) and radiation (45 to 59 Gy)
  • Arm B: Induction chemotherapy 5-FU/CDDP
  • 5-FU (1,000mg/m2 days 1-4, 29-32, 57-60 and 85-88) plus cisplatin (75mg/m2 on days 1, 29, 57 and 85) and radiation (45 to 59 Gy; start day=57)
  • Patients:
    • Squamous cell carcinoma of the anus
    • 682 accrued, 598 analyzable
  • Stratification:
    • Gender, clinical nodal status, tumor diameter
  • Endpoints:
    • Primary: Disease-free survival.
    • Powered (80%) to detect a 10% DFS difference


  • Patient characteristics were balanced between the two arms:
    • median age was 55 yrs, 69% women
    • 28% had >5 cm tumor, 26% were clinical node positive
  • Disease free survival was not significantly different
    • 5-year estimated DFS was 56% for Arm A and 48% for Arm B (p=0.28)
  • Overall survival (5-year estimated) was 69% for both arms (p=0.24)
  • Colostomy rates were higher in the CDDP/5-FU induction arm:
    • 5-year colostomy rate was 10% for Arm A and 20% for arm B(p=0.12).
  • There was no significant difference in local control (33% vs. 26%)
  • Grade 3/4 toxicity rates favored CDDP/5-FU induction arm:
    • non-hematologic toxicity was 76% for Arm A and 75% for Arm B
    • hematologic toxicity was 67% for Arm A and 47% for Arm B (p=0.0004)

Author's Conclusions

  • Induction 5-FU/cisplatin followed by 5-FU/cisplatin/radiation failed to improve DFS compared to the standard treatment, 5-FU/mitomycin/radiation
  • The colostomy rate was higher in the 5-FU/cisplatin/radiation
  • The standard treatment arm should remain the standard

Clinical/Scientific Implications

  • The DFS not only was not improved by CDDP-based induction chemotherapy, but it actually trended toward the standard arm
  • The colostomy rate difference hints at a difference in local control/late RT effects that favored the standard arm, although there was no statistically significant difference in local control