Long-term follow-up of a Phase II trial of high-dose radiation with concurrent 5-fluorouracil and cisplatin in patients with anal cancer (ECOG E4292).

Purpose Although chemoradiation using 5-fluorouracil (5-FU) and mitomycin-C (MMC) is the standard of care in the treatment of anal cancer, many patients are unable to tolerate MMC. This Phase II clinical trial was performed to determine whether cisplatin could replace MMC in the treatment of anal cancer. Methods and Materials Thirty-three patients with localized anal cancer were enrolled. One patient registered but never received any assigned therapy and was excluded from all analyses. Between February 1, 1993, and July 21, 1993, 19 patients were accrued to Cohort 1. Radiation consisted of 45 Gy to the primary tumor and pelvic nodes, followed by a boost to the primary and involved nodes to 59.4 Gy. A planned 2-week treatment break was used after 36 Gy. Concurrent chemotherapy consisted of 5-FU 1,000 mg/m 2 /day on Days 1 to 4 and cisplatin 75 mg/m 2 on Day 1. A second course of 5-FU and cisplatin was given after 36 Gy, when the patient resumed radiation therapy. Between April 4, 1996, and September 23, 1996, an additional 13 patients (Cohort 2) were accrued to the study and received the same treatment except without the planned treatment break. Results Complete response was seen in 78% (90% CI, 63–89) of patients and was higher in patients who did not get a planned treatment break (92% vs. 68%). The overall Grade 4 toxicity rate was 31%. One treatment-related death (Grade 5) occurred in a patient who developed sepsis. The 5-year overall survival was 69%. Conclusions Radiation therapy, cisplatin, and 5-FU resulted in an overall objective response (complete response + partial response) of 97%. Although the 5-year progression-free survival was only 55%, the overall 5-year survival was 69%. Given the excellent salvage provided by surgery, this study affirms that cisplatin-based regimens may be an alternative for patients who cannot tolerate the severe hematologic toxicities associated with mitomycin-based chemoradiation regimens.