A phase 2 study of irinotecan, cisplatin, and simvastatin for untreated extensive-disease small cell lung cancer.

Background: The objective of this study was to investigate the efficacy of simvastatin in combination with irinotecan and cisplatin in chemotherapy-naive patients with extensive-disease small-cell lung cancer (ED-SCLC).

Methods: In this phase 2 study, 61 patients received treatment with irinotecan (65 mg/m(2) ) and cisplatin (30 mg/m(2) ) on Days 1 and 8 every 3 weeks until either death or disease progression occurred. Patients also received oral simvastatin (40 mg daily) during the course of chemotherapy. The primary endpoint was 1-year survival. Secondary endpoints included the response rate (RR), progression-free survival (PFS), and toxicity.

Results: The 1-year survival rate was 39.3%. The median overall survival (OS) was 11 months, and the median PFS was 6.1 months. Overall, the RR was 75%. The most common grade 3/4 toxicity was neutropenia (67%). Efficacy of the treatment was associated significantly with smoking status. Compared with never-smokers, ever-smokers had a better RR (40% vs 78%; P = .01), a longer PFS (2.5 months vs 6.4 months; P = .018), and had a trend toward an improved OS (9.0 months vs 11.2 months; P = .095). The effect of smoking on survival was apparent when ever-smokers were subdivided according to pack-years (PY) of smoking. Ever-smokers who had smoked >65 PY had a significantly longer OS compared with ever-smokers who had smoked ≤65 PY or never-smokers (20.6 months vs 10.6 months vs 9.0 months, respectively; log-rank P = 0.032). In multivariate analysis, PY >65 was predictive of longer survival (hazard ratio, 0.280; 95% confidence interval, 0.113-0.694).

Conclusions: The current results indicated that simvastatin in combination with irinotecan and cisplatin did not improve the survival of patients with ED-SCLC. Although the subgroup analysis by smoking status was exploratory, the addition of simvastatin to irinotecan and cisplatin may improve the outcome of heavy smokers with ED-SCLC.