title: Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group.
abstract: OBJECTIVE
  In preclinical experiments, interferon alfa modulates the anticancer activity of fluorouracil (5-FU) and cisplatin (CDDP). To test this effect clinically in patients with recurrent or metastatic head and neck cancer (RMHNC), a multicenter randomized controlled trial with CDDP and 5-FU with or without interferon alfa-2b (IFNalpha) was performed.
  
  
  METHODS
  Eligible patients had histologically confirmed RMHNC; a good performance status; measurable disease; adequate bone marrow, hepatic, and renal function; no prior chemotherapy for recurrent or metastatic disease; only one chemotherapy regimen administered with previous local therapy; and a treatment-free interval of at least 3 months following previous local therapy. Patients were randomized and stratified according to treatment center, and prior radiotherapy and chemotherapy. The treatment regimen consisted of CDDP 100 mg/m2 on day 1 and 5-FU 1,000 mg/m2/d by continuous infusion for 96 hours (days 1 to 4), without (arm A) or with (arm B) IFNg alpha 3 x 10(6) U/d subcutaneously on days 1 to 5. Cycles were repeated every 21 days.
  
  
  RESULTS
  One hundred twenty-two patients were entered on each arm. The response rate (RR) was similar in both arms (arm A: complete response [CR] 10.7%, partial response [PR] 36.4%; arm B: CR 6.8%, PR 31.6%) (.70 < P < .50). There was no difference in median survival between the two arms (arm A 6.3 months v arm B 6.0 months; P = .49). Anorexia, fever, leukopenia, and thrombocytopenia grade III to IV were significantly more frequent in the IFNalpha arm.
  
  
  CONCLUSIONS
  Modulation of CDDP and 5-FU with IFNalpha as used in this study does not improve the RR or the median survival in patients with RMHNC. Patients on both study arms had a poor prognosis, which indicates the need for novel therapies.
authors.affiliation: Universitair Ziekenhuis Antwerpen, Antwerp, Belgium. dirk.schrijvers@uza.via.ac.be
authors.forename: D
authors.initials: D
authors.lastname: Schrijvers
authors.forename: J
authors.initials: J
authors.lastname: Johnson
authors.forename: U
authors.initials: U
authors.lastname: Jiminez
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.forename: P
authors.initials: P
authors.lastname: Kosmidis
authors.forename: H
authors.initials: H
authors.lastname: Szpirglas
authors.forename: K
authors.initials: K
authors.lastname: Robbins
authors.forename: J
authors.initials: J
authors.lastname: Oliveira
authors.forename: R
authors.initials: R
authors.lastname: Lewensohn
authors.forename: J
authors.initials: J
authors.lastname: Schüller
authors.forename: A
authors.initials: A
authors.lastname: Riviere
authors.forename: C
authors.initials: C
authors.lastname: Arvay
authors.forename: P
authors.initials: P
authors.lastname: Langecker
authors.forename: H
authors.initials: H
authors.lastname: Jacob
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
authors.forename: E
authors.initials: E
authors.lastname: Vokes
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011994:Recombinant Proteins; D012074:Remission Induction; D016019:Survival Analysis
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002945:Cisplatin; D005472:Fluorouracil