title: Cisplatin, fluorouracil, and leucovorin. Increased toxicity without improved response in squamous cell head and neck cancer.
abstract: OBJECTIVE
  To evaluate the activity and toxicity of the drug combination cisplatin, fluorouracil by continuous infusion, and high-dose oral leucovorin calcium (PFL) as induction chemotherapy in patients with advanced and untreated squamous cell head and neck (SCHN) cancer.
  
  
  METHODS
  Nonrandomized, prospective trial.
  
  
  METHODS
  Referral center (comprehensive cancer center).
  
  
  METHODS
  Twenty-two patients with stage III (n = 7) and IV (n = 15) M0 SCHN cancer of the larynx (n = 13), hypopharynx (n = 7), and oropharynx (n = 2) whose standard treatment would have required total laryngectomy.
  
  
  METHODS
  Three cycles of PFL were administered prior to local-regional therapy (concomitant cisplatin and radiation and/or neck dissection, with total laryngectomy reserved for nonresponse or relapse). Chemotherapy included cisplatin (100 mg/m2) on day 1 by short intravenous infusion; fluorouracil (800 mg/m2) on days 1 through 5 by continuous infusion; and leucovorin (100 mg) every 4 hours by mouth for 30 doses. The PFL combination was administered every 21 days.
  
  
  METHODS
  Clinical response to chemotherapy and observed toxic effects during chemotherapy.
  
  
  RESULTS
  Five patients were inevaluable for response, with three early deaths (infection in two and sudden death in one), one cerebrovascular accident, and one patient declining further chemotherapy. Of the remaining 17 patients, 10 had a major response to chemotherapy, but in only five patients (29%) was this complete (95% confidence interval, 8% to 51%). Other significant toxic effects included grade 3 to 4 mucositis in eight patients and grade 3 to 4 neutropenia in 10.
  
  
  CONCLUSIONS
  While PFL is active in patients with SCHN cancer, we were unable to reproduce the high complete response rates reported by other centers. Its use can be associated with significant toxic effects. We do not recommend the use of PFL for the treatment of patients with SCHN cancer outside the context of a clinical trial until there is further critical assessment of its activity and toxicity.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: D G
authors.initials: DG
authors.lastname: Pfister
authors.forename: D
authors.initials: D
authors.lastname: Bajorin
authors.forename: R
authors.initials: R
authors.lastname: Motzer
authors.forename: H
authors.initials: H
authors.lastname: Scher
authors.forename: C
authors.initials: C
authors.lastname: Louison
authors.forename: L
authors.initials: L
authors.lastname: Harrison
authors.forename: J
authors.initials: J
authors.lastname: Shah
authors.forename: E
authors.initials: E
authors.lastname: Strong
authors.forename: G
authors.initials: G
authors.lastname: Bosl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy*; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010610:Pharyngeal Neoplasms / Q000188:drug therapy*; D011446:Prospective Studies
chemical_list: D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil