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/m²) and cisplatin (30 mg/m²) 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. Cancer 2011. © 2010 American Cancer Society.