title: Cisplatin, fluorouracil, and L-leucovorin induction chemotherapy for locally advanced head and neck cancer: the M.D. Anderson Cancer Center experience.
abstract: OBJECTIVE
  To determine the efficacy of the combination of cisplatin, fluorouracil, and high-dose l-leucovorin (PFL) as organ-preserving induction therapy followed by radiotherapy in untreated patients with advanced squamous cell carcinoma of the head and neck.
  
  
  METHODS
  This was a phase II study of PFL in 47 patients with resectable stage III (n = 20) and IV (n = 27) M0 squamous cell carcinoma of the head and neck, including larynx (n = 20), hypopharynx (n = 14), and oropharynx (n = 13). The PFL regimen consisted of cisplatin 25 mg/m2 on days 1 through 5, fluorouracil 800 mg/m2 CI on days 2 through 6, and l-leucovorin 250 mg/m2 on days 1 through 6, all by continuous intravenous infusion every 21 to 28 days for three courses. The primary study endpoint was initial response to and local disease control rate with PFL as induction chemotherapy, with an aim to confirm the previously reported complete response rate of 60% to 70%.
  
  
  RESULTS
  Of 47 patients enrolled, 46 were evaluable for response to PFL, 14 (30%) achieved a complete response, and 25 (54%) achieved a partial response, for an overall response rate of 84%. Of 39 patients evaluable for response after radiation therapy, 27 (69%) achieved a complete response and 11 (28%) a partial response. Local disease control was achieved in 37 of 46 (80%). Grade 3 or 4 toxic effects occurred frequently, with neutropenia in 27 (59%) of 46 evaluable patients, thrombocytopenia in 30%, mucositis in 41%, diarrhea in 13%, and nausea/ vomiting in 13%, but there were no treatment-related deaths. With a median follow-up of 35 months there have been nine recurrences (four local/regional and five distant) and 17 deaths (12 in patients with disease progression and five not directly related to the primary tumor). Second primary tumors have developed in six patients. At 3 years 62% of the patients remain alive with no disease progression, and the 3-year survival estimate with preserved organ function is 66%.
  
  
  CONCLUSIONS
  PFL induction chemotherapy produced only a modest complete response rate, possibly due to suboptimal dose intensity, and was associated with substantial, although not life-threatening, toxicity. Newer regimens and treatment modalities are still needed in the management of advanced squamous cell carcinoma of the head and neck.
authors.affiliation: University of Texas M.D. Anderson Cancer Center Department of Thoracic/Head and Neck Medical Oncology, Houston 77030-4095, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Papadimitrakopoulou
authors.forename: I W
authors.initials: IW
authors.lastname: Dimery
authors.forename: J J
authors.initials: JJ
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Perez
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: S M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000528:radiation effects; D009367:Neoplasm Staging; D011832:Radiation Injuries / Q000209:etiology; D013280:Stomatitis / Q000209:etiology; D015996:Survival Rate
chemical_list: D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil