title: Phase II evaluation of 5-fluourouracil plus folinic acid and alpha 2b-interferon in metastatic colorectal cancer.
abstract: Biochemical modulation of 5-fluorouracil (5-FU) by folinic acid (FA) increases the response rate in patients with metastatic colorectal cancer compared to 5-FU alone. Phase II trials also demonstrated increased efficacy when interferon was added to 5-FU. In two consecutive trials, 76 patients were treated on days 1-5 with FA 200 mg/m2 plus interferon 5 x 10(6) U/m2 and 5-FU 350 mg/m2 as intravenous bolus injection (n = 33, regimen A) or 5-FU 500 mg/m2 as 2-hour infusion (n = 43, regimen B), repeated every 3 weeks with individual 5-FU dose escalation in steps of 50 (regimen A) or 100 mg/m2 (regimen B). In regimen A 5-FU dose reduction to 300 mg/m2 due to toxicity was necessary in 49% of the patients; in regimen B a 5-FU dose of 600 mg/m2 or above was tolerated by 70% of the patients. Dose-limiting toxicity was severe mucositis and/or diarrhea. Objective responses were observed in 5 of 33 patients (15%) in regimen A (3-28%, 95% confidence interval) and 7 of 41 patients (17%) in regimen B (5-29%, 95% confidence interval). Median time to progression was 4.7 and 4.8 months, and median survival 9.9 and 11.4 months for regimens A and B, respectively. Prolonged 5-FU administration over 2 h allows the administration of a higher 5-FU dose compared to bolus injection with no apparent improvement in antineoplastic efficacy. The addition of interferon to the combination of 5-FU plus FA in this dose and schedule does not seem to improve the response rate but appears to increase treatment toxicity.
authors.affiliation: Department of Hematology/Oncology, Hannover Medical School, Germany.
authors.forename: C H
authors.initials: CH
authors.lastname: Köhne
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: C
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: H P
authors.initials: HP
authors.lastname: Lohrmann
authors.forename: H
authors.initials: H
authors.lastname: Bodenstein
authors.forename: J
authors.initials: J
authors.lastname: Preiss
authors.forename: H
authors.initials: H
authors.lastname: Rauschecker
authors.forename: H
authors.initials: H
authors.lastname: Hill
authors.forename: C
authors.initials: C
authors.lastname: Kaufer
authors.forename: J T
authors.initials: JT
authors.lastname: Fischer
authors.forename: U
authors.initials: U
authors.lastname: Ohl
authors.forename: D
authors.initials: D
authors.lastname: Urbanitz
authors.forename: L
authors.initials: L
authors.lastname: Balleisen
authors.forename: H J
authors.initials: HJ
authors.lastname: Schmoll
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D011994:Recombinant Proteins; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil