title: A phase II trial of cisplatin, methotrexate, levofolinic acid, and 5-fluorouracil in the treatment of patients with locally advanced, metastatic squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Induction chemotherapy in locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) might improve survival with respect to radiation therapy alone. Furthermore, chemotherapy represents the only therapeutic option in metastatic head and neck carcinoma.
  
  
  METHODS
  To improve further the results that could be obtained with an induction regimen of cisplatin (CDDP) plus 5-fluorouracil (5-FU), the authors treated 50 patients with locally advanced or metastatic SCCHN with a combination of CDDP 65 mg/m2 on Day 1, methotrexate 500 mg/m2 on Day 1, levofolinic acid 250 mg/m2 on Day 2, and 5-FU 800 mg/m2 on Day 2. Cycles were repeated every 2 weeks. The authors' aim was to increase the activity of CDDP plus 5-FU (PF) using a regimen that combined the three most active drugs in SCCHN and provided an adequate biochemical modulation of 5-FU, which was administered as an intravenous bolus infusion.
  
  
  RESULTS
  Forty objective responses were observed among 50 evaluable patients (80%; 95% confidence interval [C.I.], 66-90%), including 7 complete responses (14%; 95% C.I., 5-27%), and 33 partial responses (66%; 95% C.I., 51-79%). Locoregional treatment, consisting of radiotherapy or surgery, was given at the end of chemotherapy. On completion of induction chemotherapy and locoregional treatment, 42 of 46 patients (91%) were rendered disease free. After a median follow-up of 20 months, the median duration of response was 10 months, the median failure free survival was 10 months, and the median overall survival was 21 months. The treatment was generally well tolerated. Grade 3-4 neutropenia occurred in 25 patients (50%), but it was febrile in only 3 patients. Nausea and vomiting were well managed with serotonin-3 blocking agents. Severe mucositis was seldom observed and easily manageable, and it never required hospitalization.
  
  
  CONCLUSIONS
  The high level of activity, the manageable toxicity, and the noteworthy survival data of this regimen compare favorably with most of the drug combinations used worldwide to treat similar patient populations, with the additional advantage of significantly lower cost.
authors: Medical Oncology A, National Tumor Institute G. Pascale, Napoli, Italy.
authors: F
authors: F
authors: Caponigro
authors: P
authors: P
authors: Comella
authors: P
authors: P
authors: Marcolin
authors: F
authors: F
authors: Russo Spena
authors: M
authors: M
authors: Biglietto
authors: G
authors: G
authors: Cartenì
authors: L
authors: L
authors: De Lucia
authors: A
authors: A
authors: Avallone
authors: A
authors: A
authors: Gravina
authors: G
authors: G
authors: Comella
mesh_terms: D000328:Adult; D000368:Aged; D000931:Antidotes / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D011877:Radionuclide Imaging; D016019:Survival Analysis
chemical_list: D000931:Antidotes; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate