A phase I-II study of sequential infusion VP-16 and cisplatin therapy in advanced lung cancer

Although the etoposide (VP-16) and cisplatin combination has shown therapeutic activity in lung cancer, human results to date have not matched the expectation of synergism raised by animal model studies. Laboratory studies suggest that therapeutic synergism of etoposide and cisplatin may be related to factors of drug concentration, time of exposure, and sequencing. To pursue this question, we developed regimens of etoposide given by 72 h infusion in conjunction with sequential bolus or infusion cisplatin. Thirty-two patients were entered. Fourteen of 15 small-cell lung cancer patients had a response (CR, PR, regression) with a median survival of 321 days. Nine of 17 patients with non-small-cell lung cancer achieved a response, including two CRs. The median survival is 201 days. The major toxicity was myelosuppression. At the highest etoposide dosage tested, 42% of patients had leukopenia less than 2000/mm3. There were no treatment-related deaths. This new approach of combined etoposide and cisplatin therapy shows promising therapeutic activity against both small cell and non-small-cell lung cancer.