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.
412. Evaluation of Functional p53 Biomarker Profiles Predicts Efficacy of Adenoviral p53 Gene Therapy (Advexin) in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN)