A phase II trial of carboplatin and gemcitabine with exisulind (IND #65,056) in patients with advanced non-small cell lung cancer: An Eastern Cooperative Oncology Group study (E1501)

BACKGROUND: Carboplatin and gemcitabine are one standard regimen for patients with advanced non-small cell lung cancer (NSCLC). The oral proapoptotic agent exisulind is a cyclic guanosine monophosphate phosphodiesterase that increases apoptosis in vitro. We performed a phase II trial of carboplatin and gemcitabine with exisulind in patients with advanced NSCLC. METHODS: Gemcitabine (1000 mg/m days 1 and 8) and carboplatin (AUC = 5 day 1) were administered every 21 days, with exisulind orally at 250 mg orally twice daily continuously, starting day 1. The primary objective was to evaluate the 18-month survival. Secondary objectives included response rate, progression-free survival, and toxicities. Eligibility included stage IIIB (pleural effusion) or stage IV NSCLC, no previous chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1. RESULTS: Of 57 eligible patients treated, 34 patients were male and 23 female, 42 had stage IV, six stage IIIB, and nine had recurrent disease. The median age was 63 years (range, 37-83). Twenty-six patients had an ECOG PS of 0 and 31 had a PS of 1. The majority of grade 3-4 toxicities were hematologic. Grade 3-4 nonhematologic toxicity seen in >5% of patients included nausea/vomiting in 16% and fatigue in 23% of patients. The overall response rate was 19.3%. Median progression-free survival was 4.7 months. Median overall survival was 9.0 months. Eighteen-month overall survival was 30%. CONCLUSION: The chemotherapy combination of gemcitabine and carboplatin with the oral proapoptotic agent exisulind is generally well tolerated with principally hematologic toxicity. The statistical endpoint of 17 patients alive at 18 months was met, but given ongoing developments in advanced NSCLC, ECOG will not be pursuing additional trials of exisulind in NSCLC.