Should cisplatin be avoided in the treatment of locally advanced squamous cell carcinoma of the anal canal?

Anal canal carcinoma is highly sensitive to concurrent chemoradiotherapy. Disease-free survival at 5 years, however, declines steeply with the size of the primary tumor, as well as nodal involvement. This Practice Point commentary discusses the findings of a randomized trial by Ajani et al. that compared standard chemoradiotherapy with 5-fluorouracil, mitomycin C and radiotherapy versus induction 5-fluorouracil and cisplatin followed by 5-fluorouracil plus cisplatin plus radiation therapy in the treatment of locally advanced squamous cell carcinoma of the anal canal. Differences in survival at 3 years and 5 years between the two treatments were not significant, but colostomy-free survival was significantly reduced in the induction group. Although the described induction approach should not be implemented in clinical practice, the main limitation of Ajani and colleagues' study is its design, which does not allow the question of whether cisplatin is a viable alternative to mitomycin C to be answered.