Combined-modality treatment for anal cancer. Current strategies and future directions

Background: concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and mitomycin C (MMC) is the treatment of choice for anal carcinoma. The most appropriate radiation (RT) dose, fractionation, techniques, and the most effective chemotherapy regimen (agents, number of neoadjuvant, concomitant, adjuvant cycles) remain to be established. Material and methods: this review article focuses on recent randomized trials designed to improve standard 5-FU/MMC-based CRT through the inclusion of (induction, concurrent, maintenance) cisplatin, and describes developments in combining RT with other chemotherapeutic drugs and targeted therapies. Computerized bibliographic searches of PubMed were supplemented with hand searches of reference lists and abstracts of ASCO/ASTRO/ESTRO meetings. Results: based on results of three recent randomized phase III trials, neither induction chemotherapy (RTOG 98-11, ACCORD 03) or maintenance chemotherapy with 5-FU/cisplatin (ACT II) nor RT dose escalation (ACCORD 03) improved the outcome of concurrent 5-FU/MMC-CRT. A randomized phase II trial (EORTC 22011-40014) compared concurrent 5-FU/MMC-CRT with cisplatin/MMC-CRT. The response rate of cisplatin/MMC-CRT was promising, but compliance to this regimen was limited. Current phase I/II studies are evaluating the use of capecitabine, oxalipatin, and the EGFR (epidermal growth factor receptor) inhibitor cetuximab. Conclusion: concurrent 5-FU/MMC-CRT without induction or maintenance chemotherapy remains the standard of care for anal cancer patients. (orig.)