Phase I trial of escalating doses of cisplatin in hypertonic saline.

A phase I trial of escalating doses of cisplatin (CDDP) in 3% sodium chloride was conducted to evaluate the toxicity of this method of administration. The maximally tolerated dose (MTD) was 40 mg/m2/d X 5 (200 mg/m2) in previously untreated patients, with dose-limiting leukopenia occurring on day 24 (median; range, 19 to 28). Nephrotoxicity was minimal. Ototoxicity was dose limiting in two patients. Peripheral neuropathy was observed in only one patient, but few patients received multiple courses of therapy. Six partial responses (PR) were observed in 47 patients, including two patients with refractory breast cancer and four with squamous cell carcinoma of head and neck origin. Two of the four patients with head and neck cancer had been previously treated with conventional doses of CDDP, suggesting a possible dose-response phenomenon in this disease. The saline infusion was well tolerated by older patients, suggesting that this method of administration can be safely used in those CDDP-sensitive malignancies that occur in older patients.