Chemo-biotherapy with 5-fluorouracil, leucovorin, and alpha interferon in metastatic carcinoma of the colon - A cancer biotherapy research group [CBRG] phase II study

Biochemical modulation of 5-Fluorouracil activity with Leucovorin has been well documented in colorectal cancer. Several studies have shown increased efficacy of 5-fluorouracil in combination with alpha interferon. We therefo re initiated a phase II trial of dual modulation of 5-fluorouracil with leu covorin and alpha interferon to evaluate outcomes inpatients with metastati c carcinoma of the colon. Methods: Patients with metastatic colon carcinoma with expected survival > 4 months and performance status of ECOG less than or equal to 2 were treated weekly with Leucovorin 400 mg IV followed by 5- FU 600 mg/m(2) IV bolus. Alpha interferon 3-9 million units was administere d subcutaneously every Monday, Wednesday and Friday. Patients were analyzed for toxicity, tumor response and survival. Results: Sixteen patients with a median age of 66 years were treated. Three patients were not evaluable fo r response but were evaluable for toxicity. Grades 3 and 4 toxicities were neutropenia, diarrhea, mucositis, nausea and vomiting,fatigue,fever, asthen ia and elevated hepatic enzymes. One patient died from complications associ ated with diverticulitis and neutropenia. Objective response rate was 23% ( 95% confidence interval 4-46% and median survival was 11.5 months (95% conf idence interval 6.3-19 months). Thirty-eight percent of the patients were a live at one year and 19% at two years. Conclusion: The combination of 5-flu orouracil, leucovorin and alpha interferon as administered in this phase II study did not result in enhanced response rate or survival. However this r egimen was associated with considerable toxicity.