Purpose
Treating small-cell lung cancer (SCLC) remains a therapeutic challenge. Experimental studies show
that statins exert additive effects with agents, such as cisplatin, to impair tumor growth, and
observational studies suggest that statins combined with anticancer therapies delay relapse and
prolong life in several cancer types. To our knowledge, we report the first large, randomized,
placebo-controlled, double-blind trial of a statin with standard-of-care for patients with cancer,
specifically SCLC.
Patients and Methods
Patients with confirmed SCLC (limited or extensive disease) and performance status 0 to 3 were
randomly assigned to receive daily pravastatin 40 mg or placebo, combined with up to six cycles of
etoposide plus cisplatin or carboplatin every 3 weeks, until disease progression or intolerable
toxicity. Primary end point was overall survival (OS), and secondary end points were progressionfree
survival (PFS), response rate, and toxicity.
Results
Eight hundred forty-six patients from 91 United Kingdom hospitals were recruited. The median age
of recruited patients was 64 years of age, 43% had limited disease, and 57% had extensive disease.
There were 758 deaths and 787 PFS events. No benefit was found for pravastatin, either in all
patients or in several subgroups. For pravastatin versus placebo, the 2-year OS rate was 13.2%
(95% CI, 10.0 to 16.7) versus 14.1% (95% CI, 10.9 to 17.7), respectively, with a hazard ratio of 1.01
(95% CI, 0.88 to 1.16; P = .90. The median OS was 10.7 months v 10.6 months, respectively. The
median PFS was 7.7 months v 7.3 months, respectively. The median OS (pravastatin v placebo) was
14.6 months in both groups for limited disease and 9.1 months versus 8.8 months, respectively, for
extensive disease. Adverse events were similar between groups.
Conclusion
Pravastatin 40 mg combined with standard SCLC therapy, although safe, does not benefit patients.
Our conclusions are the same as those found in all four much smaller, randomized, placebocontrolled
trials specifically designed to evaluate statin therapy in patients with cancer.