Phase II trial of the histone deacetylase inhibitor pivaloyloxymethyl butyrate (Pivanex, AN-9) in advanced non-small cell lung cancer.

This multicenter phase II trial evaluated the therapeutic activity and safety profile of pivaloyloxymethyl butyrate (Pivanex, AN-9) as a single agent in refractory non-small cell lung cancer (NSCLC). Pivanex (2.34 g/m2 per day) was administered as a 6-h continuous intravenous infusion, daily for 3 days, and repeated every 21 days until disease progression. Forty-seven patients were treated. More than 90% of patients had received both a platinum compound and a taxane and 32% had received three or more prior chemotherapy regimens. The most common toxicities were transient grade 1-2 fatigue (34%), nausea (17%), and dysgeusia (11%). Three patients had partial responses (6.4 and 95%; CI 1.4-18.7%) and 14 patients had stable disease for > or =12 weeks (30%). Median survival for all patients was 6.2 months with 1-year survival of 26%. For patients who received fewer than three prior chemotherapy regimens, median survival was 7.8 months and 1-year survival was 31%. Pivanex is well tolerated and appears to be active as a single agent in patients with advanced NSCLC refractory to previous chemotherapy. Based on its therapeutic activity and favorable safety profile, further studies of Pivanex in NSCLC, particularly in combination with current chemotherapeutic agents, are warranted.