A phase II trial of a differentiating agent (tRA) with cisplatin-VP 16 chemotherapy in advanced non-small cell lung cancer.

The prognosis for advanced non-small cell lung cancer remains poor. Response to chemotherapy is infrequent and overall survival is low. Trans-retinoic acid (tRA), a differentiating agent whose mechanism of action is thought to be different from conventional chemotherapy has activity in preclinical models and low but definite activity in the clinical setting. Its use has been hampered by decrease in bioavailability during continuous administration. We used an interrupted dosing schedule with a drug holiday for tRA that has since been confirmed to restore blood levels in combination with chemotherapy (Cisplatin-VP 16) in 20 patients with stage IIIB and IV non-small cell lung cancer. Ten patients had partial responses among 19 evaluable pts (53%; 95% confidence interval 30-75%) and 4 had minor responses. Neutropenia was the most common acute toxicity-grade 3/4 neutropenia occurring in 90% of patients at some point in the treatment course. Median survival was 25.5 weeks. This regimen of trans-retinoic acid given with drug holiday and chemotherapy has significant activity in advanced non-small cell lung cancer, is fairly well tolerated and is worthy of confirmation in a larger, multi-institutional setting.