levoleucovorin and Diverticulitis

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 therefore initiated a phase II trial of dual modulation of 5-fluorouracil with leucovorin and alpha interferon to evaluate outcomes in patients with metastatic carcinoma of the colon.. Patients with metastatic colon carcinoma with expected survival > 4 months and performance status of ECOG < or = 2 were treated weekly with Leucovorin 400 mg i.v. followed by 5-FU 600 mg/m2 i.v. bolus. Alpha interferon 3-9 million units was administered subcutaneously every Monday, Wednesday and Friday. Patients were analyzed for toxicity, tumor response and survival.. Sixteen patients with a median age of 66 years were treated. Three patients were not evaluable for response but were evaluable for toxicity. Grades 3 and 4 toxicities were neutropenia, diarrhea, mucositis, nausea and vomiting, fatigue, fever, asthenia and elevated hepatic enzymes. One patient died from complications associated with diverticulitis and neutropenia. Objective response rate was 23% (95% confidence interval 4-46%) and median survival was 11.5 months (95% confidence interval 6.3-19 months). Thirty-eight percent of the patients were alive at one year and 19% at two years.. The combination of 5-fluorouracil, leucovorin and alpha interferon as administered in this phase II study did not result in enhanced response rate or survival. However this regimen was associated with considerable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Colonic Neoplasms; Combined Modality Therapy; Diverticulitis; Drug Administration Schedule; Fatigue; Female; Fluorouracil; Gastrointestinal Diseases; Humans; Immunologic Factors; Interferon-alpha; Leucovorin; Life Tables; Male; Middle Aged; Neutropenia; Survival Analysis; Treatment Failure