Phase I trial of PALA

PALA was given iv on a weekly schedule to 32 patients with advanced malignant tumors. A course of treatment consisted of three weekly doses. Patients were treated at eight dose levels, ranging from 900 to 6750 mg/m ². Gastrointestinal toxicity (diarrhea) and skin rash were dose-limiting. No consistent myelosuppression occurred, and no renal or hepatic toxicity was observed. Two patients who did not have metastatic intracranial disease experienced episodes of encephalopathy and seizures. No major therapeutic responses were observed during this phase I trial; however, minor responses (≥ 25% tumor decrease) occurred in three patients (one with adenocarcinoma of the lung and two with epidermoid carcinoma of the bladder). Doses of 4500 mg/m ²/week for patients with a performance status ≥ 70 and 3750 mg/m ²/week for patients with a lower performance status are recommended for phase II studies.