A phase II trial of carboplatin and gemcitabine with exisulind (IND # 65,056) in patients with advanced non-small cell lung cancer: Eastern Cooperative Oncology Group Trial 1501

Abstract

7037 Background: The combination of carboplatin (CARB) and gemcitabine (GEM) is one standard regimen in advanced non-small cell lung cancer (NSCLC). The oral pro-apoptotic agent exisulind (EXI) has been shown to be well tolerated and safe, and may increase programmed tumor cell death. Methods: We studied this three drug combination on the following schedule: GEM (1000 mg/m2 days 1, 8) and CARB (AUC=5 day 1) q 21 days, with EXI given orally at 250 mg po BID on a continuous basis starting day 1 of therapy. The primary objective of this single arm phase II trial was to evaluate progression-free survival. Secondary objectives were to evaluate response rate, overall survival, and toxicities of the CARB-GEM regimen with EXI. Eligible pts had stage IIIB (malignant pleural effusion) or stage IV NSCLC with no prior chemotherapy and ECOG PS=0–2. Results: 58 pts were enrolled from October 2002 to February 2003 on this multi-institutional cooperative group study. There were 35 males and 22 females, 43 stage IV, 6 stage IIIB, and 9 with recurrent disease. The median age was 64 years (range 38–84). 26 pts had ECOG PS=0 and 32 had PS=1. The median number of cycles was 4. The principal grade 3–4 toxicities were hematologic (Table 1). Grade 3–4 non-hematologic toxicity seen in >5% of patients included: nausea 14%, and fatigue in 18% of patients. Among evaluable patients, 2 CR and 6 PR were observed for an overall RR of 17%. Median progression free survival was 4.7 months. Median overall survival was 7.1 months. Conclusions: In conclusion, GEM-CARB with the oral pro-apoptotic agent EXI is well tolerated with mainly hematologic toxicity. This regimen does not, however, show evidence of a benefit over standard chemotherapy and will be abandoned by ECOG for further study in NSCLC. Ongoing studies will evaluate its activity in other tumor types and stages. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly; Bristol-Myers Squibb