From Guidelines to Practice: Clinical Perspectives on Mitomycin-Based Chemoradiation for Anal Cancer

Evolution of Treatment Protocols

The treatment evolution for anal cancer began in the 1970s with the Nigro regimen, combining 5-fluorouracil and mitomycin with radiation therapy, which demonstrated the potential to spare surgery through chemoradiation alone. This landmark study showed 79% complete clinical response rates in locally advanced disease, with pathological complete responses in patients who underwent subsequent surgery. The regimen established chemoradiation as the definitive treatment approach for locally advanced anal cancer.

Recent advances include the 2019 InterAACT study, a phase 2 trial comparing carboplatin/paclitaxel vs 5-FU/cisplatin in metastatic disease, showing improved progression-free survival and tolerability with the carboplatin regimen. The most significant development is the 2025 PODIUM-303 study, the first large phase 3 global trial incorporating checkpoint inhibitors with chemotherapy in metastatic anal cancer, representing a paradigm shift toward immunotherapy integration.

Current NCCN guidelines recommend the Nigro regimen (5-FU and mitomycin with radiation) as the preferred approach for locally advanced disease, with capecitabine as an alternative to 5-FU based on smaller studies and retrospective analyses. The evolution from 3-week radiation protocols to modern intensity-modulated radiation therapy techniques delivering 70 Gy over 6 weeks has improved treatment precision and outcomes while maintaining the core chemotherapy backbone established decades earlier.