title: alpha-Interferon and 5-fluorouracil: possible mechanisms of antitumor action.
abstract: We have treated 17 patients with 5-fluorouracil (5-FU, 300 mg/m2/d by continuous ambulatory infusion for 8 weeks) and interferon alfa-2b (escalating doses to cohorts of three to five patients, given subcutaneously on a daily schedule at 2.0, 3.5, 5.0, and 10.0 x 10(6) IU/m2). The two major toxicities observed were mucositis, which occurred in 10 patients at 2 weeks and required interruption of therapy and 5-FU dose reduction, and chronic fatigue syndrome, which required reduction of the dose of interferon alfa-2b. Other toxicities seen included elevation in BUN/creatinine, elevation in liver function tests, alopecia, diarrhea, confusion, and myelosuppression. No toxic deaths occurred. Five responses were observed: two complete responses, two partial responses, and one minor response, all in patients with gastrointestinal malignancy; three of the responding patients had previously failed 5-FU-containing regimens. When we measured 5-FU plasma levels in nine of our patients, they were at or below 1 ng/mL in most patients; however, within 1 hour of administration of interferon alfa-2b, plasma levels rose 16-fold. This elevation of 5-FU levels persisted for at least 24 hours, and could not be accounted for on the basis of altered interleukin-6 levels. When the regimen was tested in eight patients with metastatic renal cell carcinoma as part of a pilot study, three partial responses were observed, and no patient developed disease progression while on treatment. The combination of 5-FU, given by continuous infusion, and interferon alfa-2b, given daily, appears worthy of advancement to phase II trials.
authors.affiliation: Division of Medical Oncology, School of Medicine, University of North Carolina, Chapel Hill.
authors.forename: L M
authors.initials: LM
authors.lastname: Meadows
authors.forename: P
authors.initials: P
authors.lastname: Walther
authors.forename: H
authors.initials: H
authors.lastname: Ozer
mesh_terms: D002986:Clinical Trials as Topic; D004357:Drug Synergism; D005472:Fluorouracil / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil