Intrapleural etoposide for malignant effusion

The pharmacology, toxicity, and therapeutic effectiveness of etoposide (VP-16) given by the intrapleural route were examined in a phase I trial. Ten patients with malignant pleural effusion received 100, 150, or 225 mg/m2 VP-16 infused over 2 h into the pleural space after drainage of pleural fluid. The administration of VP-16 was tolerated well, with no local pain, increase in cough, dyspnea, or infection. Myelosuppression was mild at doses of 150 mg/m2 or less but severe at 225 mg/m2. Drug levels were followed in both plasma and pleural fluid for up to 12 h. Clearance of VP-16 from the pleural cavity was low at 2 ml/min m2. Peak pleural-fluid drug levels in patients receiving 225 mg/m2 exceeded 300 micrograms/ml, whereas peak drug concentrations in corresponding plasma samples obtained at the same time amounted to less than 10 micrograms/ml. Serial chest X-rays showed no disappearance of pleural effusion in nine evaluable patients. However, follow-up investigation of pleural fluid characteristics [carcinoembryonic antigen (CEA), lactic dehydrogenase (LDH), and cytologic examination] suggested some evidence of local therapeutic benefit.