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 aid) plus recombinant interferon alfa-2a have demonstrated this combination's major activity against advanced squamous cell carcinoma 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 patients with measurable metastatic colon carcinoma who had received no previous chemotherapy were entered on the trial. Patients received recombinant interferon alfa-2a, 6 million units a day subcutaneously, and isotretinoin, 1 mg/kg per day orally in two divided doses. Patients were evaluated 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 responses in measurable pulmonary metastases lasting 12 and 8 weeks. Grade 3-4 toxic reactions included fatigue (5 patients), granulocytopenia (6 patients), neurotoxicity (2 patients), and elevated serum triglyceride levels (2 patients). Although this combination has demonstrated significant activity in squamous cell carcinomas of the skin and cervix, our results suggest that it has little therapeutic activity against advanced colorectal adenocarcinomas.