Porfiromycin less effective than mitomycin C as chemoradiotherapy

Porfiromycin is not as effective as mitomycin C as chemoradiotherapy in patients with squamous cell cancer of the head and neck, in spite of promising preclinical results, a randomised trial suggests. Concurrent chemotherapy and radiation improves local or regional control and disease-free survival in squamous cell cancer of the head and neck (SCCHN) but there is no specific chemotherapy standard of care. Failure of radiation to control local disease may be due to the presence of relatively radioresistant hypoxic cells. Mitomycin C is a hypoxic cell cytotoxic and the methylated derivative porfiromycin (POR) has been shown to have greater differential hypoxic cell cytotoxicity. This randomised controlled trial of 128 patients with SCCHN referred for radiation therapy at a multidisciplinary centre, were treated with external beam radiation and 60 patients were randomised to radiation and porfiromycin and 61 to radiation and mitomycin C. Results showed no significant differences between groups in toxicity. Five-year actuarial local relapse free survival was 91.6% in the mitomycin C group and 72.7% in the POR group (p = 0.01), local or regional relapse free survival was 82% and 65% (p = 0.05) and disease-free survival was 72.8% and 52.9% (p=0.026). There was no difference between groups in distant metastasis free survival, cause specific survival or overall survival. Subgroup analysis of patients with primary radiation therapy or post operative radiation showed consistent outcomes between groups. The authors concluded that the results did not confirm the promising preclinical findings and suggested that the study demonstrates the importance of confirming preclinical and clinical data with randomised trials. The reason for the lack of effectiveness was unclear but they note that they are no longer evaluating POR in head and neck Cancer.Reference...