title: A phase I trial of 5-fluorouracil, leucovorin and interferon-alpha 2b administered by 24 h infusion in metastatic colorectal carcinoma.
abstract: A phase I trial of 5-fluorouracil (5-FU), leucovorin (LV) and interferon (IFN) was conducted in 15 advanced colorectal cancer patients refractory to a bolus regimen of 5-FU/LV. Therapy consisted of a weekly i.v. infusion of 5-FU at 2600 mg/m2 administered concomitantly with LV at 500 mg/m2 over a 24 h period. IFN-alpha 2b was administered by 24 h infusion from the second cycle at escalating dose (4.5, 9, 18 and 27 MU/m2). The maximum tolerated dose of IFN was 18 MU/m2. At 27 MU/m2 two patients complained of diarrhea grade 3, so that the escalation of IFN dose was stopped. Two patients achieved a partial response (IFN level dose 9-18 MU/m2). Eight patients had stable disease. Pharmacokinetics of 5-FU were not influenced by IFN at any level dose. Our results show that doses of IFN of 18 MU/m2 given by a 24 h infusion can be administered safely to an established and active schedule of weekly 24 h infusion of 5-FU and LV. A phase II study has been planned to define the level of activity of this regimen.
authors.affiliation: Servizio di Oncologia Medica, Azienda Ospedaliera S Salvatore, Pesaro, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
authors.forename: E
authors.initials: E
authors.lastname: Del Ferro
authors.forename: M
authors.initials: M
authors.lastname: Ligi
authors.forename: G
authors.initials: G
authors.lastname: Catalano
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019540:Area Under Curve; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D002955:Leucovorin / Q000008:administration & dosage; D007970:Leukopenia / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013280:Stomatitis / Q000139:chemically induced
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil