Concurrent chemo-radiotherapy with mitomycin C compared with porfiromycin in squamous cell cancer of the head and neck: Final results of a randomized clinical trial

Purpose: Previous randomized trials have shown a benefit with concurrent use of the hypoxic cell cytotoxin mitomycin C (MC) and radiation (RT) in the management of squamous cell cancer of the head and neck (SCCHN). We conducted a randomized trial comparing MC with porfiromycin (POR) in combination with RT in the management of SCCHN. Methods and Materials: Between 1992 and 1999, 128 patients with SCCHN were enrolled in this prospective randomized trial. Patients were stratified by management intent, and balanced with respect to stage and site of disease. They were randomized to receive MC (15 mg/M-2) or POR (40 mg/M-2) on Days 5 and 47 (or last day) of RT. Of 121 evaluable patients, 61 were randomized to MC and 60 to POR. Patients were treated with standard daily RT to a total median dose of 64 Gy over 47 days. Patients were well balanced with respect to management intent, stage, site, age, sex, hemoglobin levels, tumor grade, radiation dose, and days on treatment. Results: There were no significant differences between the two arms with respect to acute hematologic or nonhematologic toxicities. As of January 2003 with a median follow-up of 6.3 years, there have been 19 local relapses (4 MC vs. 15 POR), 21 regional relapses (7 MC vs. 14 POR), 24 distant metastases (11 MC vs. 13 POR), and 66 deaths (33 MC vs. 33 POR). MC was superior to POR with respect to 5-year local relapse-free survival (91.6% vs. 72.7%, p = 0.01), local-regional relapse-free survival (82% vs. 65.3%, p = 0.05), and disease-free survival (72.8% vs. 52.9%, p = 0.026). There were no significant differences between the two arms with respect to overall survival (49.2% vs. 54.4%) or distant metastasis-free rate (79.9% vs. 75.9%). Conclusions: Despite promising preclinical data, and an acceptable toxicity profile, POR was inferior to MC as an adjunct to RT in the management of SCCHN. This randomized trial emphasizes the need for randomized studies to evaluate new agents in the management of SCCHN. (C) 2005 Elsevier Inc.