Mitomycin based chemoradiotherapy for treatment of anal canal carcinoma

Results of US Gastrointestinal Intergroup trial RTOG 98-11 do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma. Chemoradiation is the preferred primary therapy for patients with anal canal carcinoma, and it is more effective for smaller rather than larger tumours. The 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is approximately 65%. The aim of this study was to see if induction chemotherapy to downsize the tumour would be effective prior to concurrent chemoradiation, in local control and colostomy free survival. This multicentre, phase III, randomised controlled trial compared treatment with fluorouracil (1000 mg/m2) plus mitomycin and (10 mg/m2) and radiotherapy (45-59 Gy), with the experimental group of treatment with fluorouracil (1000 mg/m2) plus cisplatin (75 mg/m2) induction chemotherapy followed by the same chemotherapy and concurrent radiotherapy (45-59 Gy7) in 682 patients with anal canal carcinoma. Primary end point was 5-year disease-free survival. At the time of second interim analysis, even with the extra specified events, data could not show a statistically significant survival difference between groups, and the data monitoring committee recommended reporting the study results. The median follow-up for all patients was 2.51 years, and 644 patients were assessable. Median age was 55 years, 69% were women, 27% had a tumour diameter greater than 5 cm, and 26% had clinically positive nodes. The 5-year disease-free survival rate was 60% in the mitomycin-based group and 54% in the cisplatin-based group (p = 0.17).Three year overall survival was 84% and 75% and 5-year overall survival was 75% and 70% respectively (p = 0.10). Independent risk factors for disease free and overall survival were male sex, clinically positive nodes and size greater than 5 cms, but not treatment or tumour location. The 5-year local-regional recurrence was 25% and 33%, and distant metastasis rates were 15% and 19% in the mitomycin an dcisplatin based groups respectively. The 3 and 5 year cumulative rate of colostomy was 16% and 19% in the mitomycin-based group and 10% for both in the cisplatin-based group (p = 0.02). Severe haematologic toxicity was worse in the mitomycin-based treatment (p < 0.001). The authors concluded that cisplatin-based therapy did not improve disease-free-survival compared with mitomycin-based therapy, and resulted in a significantly worse colostomy rate. They noted that the trial was not set up to quantify the actual downsizing produced, but had assumed that it would translate into improved survival. They noted that the results reinforce the need for randomised controlled trials to test hypotheses, as assumptions from uncontrolled experiences may turn out to be incorrect. Reference...