PHASE-II TRIAL OF ISOTRETINOIN AND RECOMBINANT INTERFERON ALFA-2A IN METASTATIC COLORECTAL-CARCINOMA

Phase II trials of the novel biologic combination isotretinoin (13-cis -retinoic acid) plus recombinant interferon alfa-2a have demonstrated this combination's major activity against advanced squamous cell carci nomas of the skin and cervix. Because this combination has had limited study in other tumors, we initiated a phase II trial of this regimen in patients with metastatic colorectal adenocarcinoma. Sixteen patient s with measurable metastatic colon carcinoma who had received no previ ous chemotherapy were entered on the trial. Patients received recombin ant interferon alfa-2a, 6 million units a day subcutaneously, and isot retinoin, 1 mg/kg per day orally in two divided doses. Patients were e valuated for response after 8 weeks of treatment and then continued on therapy until progressive disease was documented. We did not observe complete or partial responses. Two patients experienced minor response s in measurable pulmonary metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5 patients), granulocytopenia (6 pa tients), neurotoxicity (2 patients), and elevated serum triglyceride l evels (2 patients). Although this combination has demonstrated signifi cant activity in squamous cell carcinomas of the skin and cervix, our results suggest that it has little therapeutic activity against advanc ed colorectal adenocarcinomas.