Treatment results for malignant skull base lesions may be improved with combined modality therapy. Using a novel drug infusion technique that capitalizes on the pharmacodynamic cisplatin-neutralizing properties of thiosulfate, 14 patients (6 untreated, 8 recurrent) received cisplatin (120 to 200 mg/m(2) for 1 to 4 weeks x 2-4 cycles) as part of a multimodality treatment program. Histology included squamous cell carcinoma, 11 patients (8 upper aerodigestive tract, 3 cutaneous); sarcoma, 2 patients (malignant fibrous histiocytoma, synovial cell sarcoma); and salivary gland cancer, 1 patient. The lesions involved the lateral skull base (12 patients) and the anterior (2 patients).Dose intensities for cisplatin were between 33.3 and 200 mg/m(2)/wk. Major responses occurred in 9/14 patients (64.3%), 3 of whom had complete responses. Drug toxicity, occurring in 11 patients, was mild and there were no significant complications as a result of the infusions. Eleven patients subsequently underwent surgical resections. The mean survival time is 23.3 months. Eight patients are alive without disease, 2 alive with disease, and 4 are dead of disease.The effectiveness of this highly selective supradose cisplatin infusion technique and its low morbidity support continued investigations of its application to patients with cranial base malignancies.