Phase I/II study of vinorelbine and exisulind as first-line treatment of advanced non-small cell lung cancer in patients at least 70 years old: a wisconsin oncology network study.

Exisulind is an apoptotic agent with preclinical activity in non-small cell lung cancer (NSCLC). Vinorelbine is safe and effective in older patients with advanced NSCLC. We assessed these agents together as palliative treatment for older patients with advanced NSCLC. Chemotherapy-naive patients >/=70-years-old with stage IIIB-IV NSCLC and a performance status (PS) </=2 were eligible. Primary endpoints were the maximum tolerated dose (phase I) and time-to-progression (phase II) of oral exisulind with 25 mg/m/wk of intravenous vinorelbine on a 28-day cycle. Patients with clinical benefit after 6 cycles of this combination received exisulind alone. Fourteen phase I patients (median PS 1; median age 78 years) were enrolled. Dose-limiting toxicities included grade 3 constipation (one patient), grade 3 febrile neutropenia (one patient) and grade 3 diarrhea (one patient). The maximum tolerated dose of oral exisulind with 25 mg/m/wk of intravenous vinorelbine was 125 mg twice daily. Thirty phase II patients (median PS 1; median age 78 years) were enrolled. Grade >/=3 neutropenia occurred in 14/30 patients. Two patients experienced neutropenic fever. There were no complete responses, one partial response and 12 patients with stable disease as their best response. The objective response rate was 4.0% (95% CI: 0.1-20.4%). Phase II median time-to-progression was 4.7 months (95% CI: 3.1-9.3 months) and median OS was 9.6 months (95% CI: 6.6-19.1 months). This combination is safe, seems to have activity in the elderly with advanced NSCLC and a PS </=2, and warrants further investigation.