title: A phase I study of escalating interferon alpha-2a combined with 5-fluorouracil and leucovorin in patients with gastrointestinal malignancies.
abstract: On the basis of preclinical data showing synergy between 5-fluorouracil (5-FU), leucovorin (LV) and IFN-alpha-2a, a phase I study was carried out to determine the maximum tolerable dose (MTD) of IFN-alpha-2a with this combination in patients with gastrointestinal malignancies. The treatment consisted of 370 mg/m2 5-FU and 200 mg/m2, LV on days 1 to 5, and IFN-alpha-2a on days 1 to 5 of the first week of chemotherapy and on days 1, 3, 5 of each subsequent week, on a 28-day cycle. Six patients with colorectal, 3 with pancreas, 2 with oesophagus, 2 with hepatocellular and one with gastric cancer were treated. At level III (5 x 10(6) U/m2) all patients experienced grade 3 or 4 toxicity during the first 56 days of treatment and the MTD was declared level II. Grade 3 toxicity comprised of anorexia, mucositis, diarrhoea, and fatigue; in one instance, grade 4 neutropenia occurred. Ten patients were evaluable for response, one patient with an oesophageal cancer had a minor response and one patient with rectal cancer and liver metastases had a radiological complete response lasting 3 months. The recommended dose for this schedule in phase II studies is 5-FU 370 mg/m2, LV 200 mg/m2, and IFN-alpha-2a 4 x 10(6) U/m2.
authors.affiliation: Department of Oncology, McGill University, Montreal, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Trudeau
authors.forename: A
authors.initials: A
authors.lastname: Zukiwski
authors.forename: A
authors.initials: A
authors.lastname: Langleben
authors.forename: G
authors.initials: G
authors.lastname: Boos
authors.forename: K
authors.initials: K
authors.lastname: Hayden
authors.forename: G
authors.initials: G
authors.lastname: Batist
mesh_terms: D000328:Adult; D000368:Aged; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil