title: Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma.
abstract: OBJECTIVE
  To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study.
  
  
  METHODS
  Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity.
  
  
  RESULTS
  Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity.
  
  
  CONCLUSIONS
  This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.
authors.affiliation: Clinical Oncology Program, National Cancer Institute, Bethesda, MD.
authors.forename: J L
authors.initials: JL
authors.lastname: Grem
authors.forename: E
authors.initials: E
authors.lastname: Jordan
authors.forename: M E
authors.initials: ME
authors.lastname: Robson
authors.forename: R A
authors.initials: RA
authors.lastname: Binder
authors.forename: J M
authors.initials: JM
authors.lastname: Hamilton
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: S G
authors.initials: SG
authors.lastname: Arbuck
authors.forename: R A
authors.initials: RA
authors.lastname: Beveridge
authors.forename: A N
authors.initials: AN
authors.lastname: Kales
authors.forename: J A
authors.initials: JA
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; 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; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D016019:Survival Analysis
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002955:Leucovorin; D005472:Fluorouracil