title: A phase II trial of interferon alpha-2b with folinic acid and 5-fluorouracil administered by 4-hour infusion in metastatic colorectal carcinoma.
abstract: Preclinical data suggest that folinic acid as well as interferon alpha-2b may enhance the antitumor activity of 5-fluorouracil (5-FU). In a phase I trial, we recently showed that interferon alpha-2b (IFN), folinic acid and 5-FU can be safely administered with a 4-hour infusion of 5-FU. We therefore initiated a phase II trial evaluating the efficacy and safety of these three drugs. Forty-five evaluable patients with advanced metastatic colorectal cancer, documented progressive disease, and previously unexposed to chemotherapy were treated with sequential IFN 5 MU/d subcutaneously and folinic acid 200 mg/m2/d as bolus on days 1 to 7 followed by 5-FU in a 4-hour infusion at a dose of 500 mg/m2/d, resulting in a total dose of 3,500 mg/m2/course. This schedule was repeated on day 21. A total of 204 courses of therapy were completed. One of 45 patients (2%) achieved a complete response, and 13 of 45 patients (29%) achieved a partial response. An additional 16 patients (36%) had stable disease. The median time to disease progression was seven months (2 to 24 months). Despite the relatively high-dose intensity of 5-FU, toxicity was very mild. Grade 3 or 4 myelosuppression, stomatitis, and nausea/vomiting occurred in only three of 45 patients (7%). Four of 45 patients (9%) suffered from severe (grade 3/4) diarrhea. Neurotoxicity and infections of grade 2 to 4 did not occur. From these data we conclude that modulation of 5-FU with both folinic acid and IFN induces an overall response rate of 31% in disseminated colorectal cancer. Using a 4-hour application schedule of 5-FU, the therapeutic index can be improved even for high-dose intensity and requires further evaluation in combination with other modulators.
authors.affiliation: Department of Hematology and Oncology, Free University of Berlin, Germany.
authors.forename: E D
authors.initials: ED
authors.lastname: Kreuser
authors.forename: R U
authors.initials: RU
authors.lastname: Hilgenfeld
authors.forename: M
authors.initials: M
authors.lastname: Matthias
authors.forename: B
authors.initials: B
authors.lastname: Hoksch
authors.forename: C
authors.initials: C
authors.lastname: Boewer
authors.forename: B
authors.initials: B
authors.lastname: Oldenkott
authors.forename: H
authors.initials: H
authors.lastname: Lenk
authors.forename: N
authors.initials: N
authors.lastname: Wiener
authors.forename: J
authors.initials: J
authors.lastname: Boese-Landgraf
authors.forename: A
authors.initials: A
authors.lastname: Schalhorn
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil