Background
Phase III RCT (n=682) of squamous, basaloid, or cloacogenic carcinoma of the anal canal, T2–T4 any N. Compared mitomycin-based vs cisplatin-based concurrent chemoradiotherapy. Excluded T1 or M1 disease, severe comorbidity, AIDS, or major untreated malignancy.
Interventions and follow up
Arm A: fluorouracil 1000 mg/m2 D1–4 and 29–32 + mitomycin 10 mg/m2 D1 and 29, with concurrent radiotherapy (45–59 Gy)
Arm B: fluorouracil 1000 mg/m2 D1–4, 29–32, 57–60, 85–88 + cisplatin 75 mg/m2 D1, 29, 57, 85; radiotherapy (45–59 Gy) starting day 57 (induction then concurrent)
Primary endpoint: 5-year disease-free survival (DFS)
Median follow up: 2.5 years
Arm B: fluorouracil 1000 mg/m2 D1–4, 29–32, 57–60, 85–88 + cisplatin 75 mg/m2 D1, 29, 57, 85; radiotherapy (45–59 Gy) starting day 57 (induction then concurrent)
Primary endpoint: 5-year disease-free survival (DFS)
Median follow up: 2.5 years
Results
5-yr DFS: 60% vs 54%, arm A vs B; P=.17
5-yr OS: 75% vs 70%, arm A vs B; P=.10
5-yr colostomy rate: 10% vs 19%, arm A vs B; P<.001
3-yr OS: 84% vs 76%, not significant
5-yr OS: 75% vs 70%, arm A vs B; P=.10
5-yr colostomy rate: 10% vs 19%, arm A vs B; P<.001
3-yr OS: 84% vs 76%, not significant
Adverse events
Grade ≥3 hematologic: 61% vs 42% (arm A vs B), higher with mitomycin
Grade ≥3 non-hematologic: 74% in both groups, predominantly gastrointestinal and skin toxicity
Grade ≥3 non-hematologic: 74% in both groups, predominantly gastrointestinal and skin toxicity
Conclusions
In anal canal carcinoma excluding T1/M1 disease, mitomycin-based chemoradiotherapy yielded better disease-free survival and lower colostomy rate than cisplatin-based therapy, despite greater hematologic toxicity.
Key Limitations
The two arms differed in both drug and radiotherapy schedule (induction cisplatin delayed RT start to day 57), confounding the cisplatin vs mitomycin comparison. DFS and OS differences were not statistically significant.
Clinical Context
Reaffirmed 5-FU/mitomycin plus radiotherapy as the standard definitive treatment for localized anal squamous cell carcinoma, consistent with the UK ACT II trial. Endorsed across ASCO/ESMO guidance for anal cancer.