RTOG 87-04/ECOG
Needs reviewRole of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation, in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: phase III randomized intergroup study (RTOG/ECOG)
Phase 3N = 310
- Population
- Patients with epidermoid carcinoma of the anal canal
- Design
- Phase III randomised intergroup trial of the Radiation Therapy Oncology Group (RTOG) and Eastern Cooperative Oncology Group (ECOG). Between August 1988 and December 1991, 310 patients were randomised to radiotherapy plus fluorouracil, or radiotherapy, fluorouracil and mitomycin. Of 291 assessable patients, 145 received 45 to 50.4 Gy of pelvic radiotherapy plus fluorouracil 1,000 mg/m2/day for 4 days and 146 received the same with mitomycin (10 mg/m2 per dose, two doses). Patients with residual tumour on post-treatment biopsy were treated with salvage chemoradiation: additional pelvic radiotherapy (9 Gy), fluorouracil and cisplatin (100 mg/m2).
- Arms
- Radiotherapy with fluorouracil (control, n = 145): 45 to 50.4 Gy pelvic radiotherapy plus fluorouracil 1,000 mg/m2/day for 4 days
- Radiotherapy with fluorouracil and mitomycin (experimental, n = 146): 45 to 50.4 Gy pelvic radiotherapy plus fluorouracil 1,000 mg/m2/day for 4 days and mitomycin 10 mg/m2 per dose for two doses
- People
- Flam M, senior author Murray K, Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group
Δ 48-month DFS+22 pointsΔ 48-month Colostomy-free survival+12 pointsΔ 48-month Colostomy rate−13 pointsΔ Grade 4 or 5 toxicity+16 points
Show the numbers
| Endpoint | Analysis | Radiotherapy with fluorouracil and mitomycin | Radiotherapy with fluorouracil | Effect |
|---|---|---|---|---|
| DFS291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised; the abstract does not state whether the analysis was by intention to treat | primaryFlam 1996 | 73% at 4 y | 51% at 4 y | P=.0003Disease-free survival at 4 years. Posttreatment biopsies were positive in 15% of patients in the fluorouracil arm and 7.7% in the mitomycin arm (P = .135). A significant difference in overall survival was not observed at 4 years (no overall survival figures are given in the abstract). Of 24 assessable patients who underwent salvage chemoradiation, 12 (50%) were rendered disease-free. |
| Colostomy-free survival291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised | primaryFlam 1996 | 71% at 4 y | 59% at 4 y | P=.014Colostomy-free survival at 4 years. |
| Colostomy rate291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised | primaryFlam 1996 | 9% at 4 y | 22% at 4 y | P=.002Colostomy rates at 4 years were lower in the mitomycin arm. |
| Grade 4 or 5 toxicity291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised | primaryFlam 1996 | 23% | 7% | P=≤ .001The abstract reports 23% vs 7% as grade 4 and 5 toxicity (combined) and the value is recorded as published. A 2026 review of the trial reports, for the mitomycin arm, 34 of 146 patients (23%) with grade 4 and 4 (3%) with grade 5 toxicity, which does not match the abstract's description of 23% as grade 4 and 5 combined; the full text could not be read to reconcile them. |
| Endpoint | Analysis | Radiotherapy with fluorouracil and mitomycin | Radiotherapy with fluorouracil | Effect |
|---|---|---|---|---|
| DFS291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised; the abstract does not state whether the analysis was by intention to treat | primaryFlam 1996 | 73% at 4 y | 51% at 4 y | P=.0003Disease-free survival at 4 years. Posttreatment biopsies were positive in 15% of patients in the fluorouracil arm and 7.7% in the mitomycin arm (P = .135). A significant difference in overall survival was not observed at 4 years (no overall survival figures are given in the abstract). Of 24 assessable patients who underwent salvage chemoradiation, 12 (50%) were rendered disease-free. |
| Colostomy-free survival291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised | primaryFlam 1996 | 71% at 4 y | 59% at 4 y | P=.014Colostomy-free survival at 4 years. |
| Colostomy rate291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised | primaryFlam 1996 | 9% at 4 y | 22% at 4 y | P=.002Colostomy rates at 4 years were lower in the mitomycin arm. |
| Grade 4 or 5 toxicity291 assessable patients (145 fluorouracil, 146 fluorouracil and mitomycin) of 310 randomised | primaryFlam 1996 | 23% | 7% | P=≤ .001The abstract reports 23% vs 7% as grade 4 and 5 toxicity (combined) and the value is recorded as published. A 2026 review of the trial reports, for the mitomycin arm, 34 of 146 patients (23%) with grade 4 and 4 (3%) with grade 5 toxicity, which does not match the abstract's description of 23% as grade 4 and 5 combined; the full text could not be read to reconcile them. |
Appears in
Sources
Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S, et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996;14(9):2527-39.