A phase III randomized placebo controlled NCCTG trial of carboxyaminoimidazole (CAI) in patients with advanced non-small cell lung cancer (NSCLC)

Abstract

7054 Background: Benefit from chemotherapy (ctx) for NSCLC has plateaued. Agents with novel mechanisms may provide further gain. CAI has in-vitro effects including inhibition of tumor cell motility, adhesion, and growth. Methods: CAI/placebo at 250 mg/day was given orally as maintenance therapy in stage 3 or 4 NSCLC patients within 6 weeks of completion of first line ctx (Stage 3 patients may have received thoracic radiotherapy). Eligible patients had stable or responding disease to one ctx regimen of 3–6 months (mo) duration; ECOG performance status of 0,1,2; absence of untreated brain metastases and adequate hematologic, hepatic and renal function. The study closed early due to slow accrual (targeted 360, observed 186). 360 patients followed for a minimum of 1 year would have provide 80% power to detect a 40% increase in the primary endpoint of median survival with a two-sided 5% type I error rate. The 154 observed deaths in the 186 patients accrued provide 80% power to detect a 60% increase in median survival. Results: Between 4/99 and 8/04, 186 patients (94 CAI, 92 placebo) were randomized with balance in median age, performance status, gender, histology, stage and response status to initial ctx. Incidence of severe (grade 3+) adverse events (AE) was not significantly different for CAI compared to placebo (42% vs. 34%, p=0.24). AE (primarily grade 1,2) observed more often in the CAI group included fatigue (55.6% vs 29.4%, p=0.0003), anorexia (31.1% vs 13.0%, p=0.003), nausea (61.1% vs 30.4%, p<0.0001), and vomiting (32.2% vs 14.1%, p=0.004); and grade 3+ AE included neurosensory (8.5% vs. 0.0%, p=0.004) and ataxia (11.1% vs. 3.3%, p=0.05). Patients discontinued treatment for AE/refusal more often in the CAI group (34.5% vs 6.8%, p<0.0001). Median follow-up is 20.0 mo. Both median survival and time to progression are not significantly different between the two groups (11.8 mo vs 10.5 mo, p= 0.93; 3.2 mo vs 2.5 mo, p=0.88). Conclusion: The addition of CAI following chemotherapy does not provide clinical benefit over placebo in advanced NSCLC. No significant financial relationships to disclose.