title: Sequential methotrexate, 5-fluorouracil, and cisplatin in the treatment of recurrent squamous-cell carcinoma of the head and neck: failure of hypertonic saline to reduce the nephrotoxicity of cisplatin.
abstract: Fifty patients with histologically proven squamous-cell carcinoma of the head and neck, recurrent after surgery and/or radiation therapy, were treated with a triple-drug combination of methotrexate (MTX), 250 mg/m2 intravenously (IV) on day 1, followed by 5-fluorouracil (5-FU), 600 mg/m2 IV on days 1 and 2, followed by cisplatin, 50 to 60 mg/m2 IV on days 3 and 4. Patients were randomly assigned to receive cisplatin either in 300 mL of 3% saline or with standard mannitol diuresis along with appropriate hydration. The courses of treatment were repeated every 3 to 4 weeks. Among 47 evaluable patients, there were four complete responses (CRs) and 17 partial responses (PRs) (9% and 36%, respectively). The median duration of response was 23 weeks and the overall survival was 7 months. The median survival of responders v nonresponders was 12 months and 6 months, respectively. Nausea and vomiting was experienced by all patients and diarrhea was experienced by 36% of patients. Neutropenia occurred in 37 patients (79%) and resulted in fever or infection in 11 patients (23%) and death in two patients. Mild renal failure (persistent serum creatinine greater than 1.5 mg/ dL) was observed in ten patients (21%), six treated with 3% saline and four treated with mannitol. The median cumulative dose of cisplatin that lead to the development of renal impairment was 485 mg/m2 in the hypertonic saline arm and 550 mg/m2 in the mannitol arm (P = .40). The antitumor activity of this regimen was not superior to that of sequential MTX and 5-FU. The use of hypertonic saline was not effective in reducing the renal toxicity of cisplatin.
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008353:Mannitol; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D011897:Random Allocation; D012965:Sodium Chloride
chemical_list: D008353:Mannitol; D012965:Sodium Chloride; D002945:Cisplatin; D005472:Fluorouracil; D008727:Methotrexate