390P - A Prospective, Randomized, Placebo Controlled Study of Simvastatin/Chemotherapy Effectiveness in Metastatic Breast Cancer Patients

Abstract

ABSTRACT Aim: Statins, cholesterol lowering and anti-inflammatory agents, have demonstrated an in-vitro anti-tumor activity, but clinical evidence is lacking. Our study aimed at evaluating the postulated chemo-sensitizing effect of simvastatin in a cohort of metastatic breast cancer (MBC) patients. Methods: This was a prospective, single-centered, randomized, double blinded, placebo controlled study. The study protocol was approved by the Scientific Research Ethics Committee at Damascus University. Inclusion criteria encompassed MBC patients undergoing a chemotherapy course consisting of carboplatin and vinorelbine, and with an ECOG Performance Status score > 2. Patients were enrolled between August 2011 and July 2012, and randomly allocated to receive oral simvastatin 40 mg or placebo for 15 days starting at day -7 of each chemotherapy cycle. The follow-up duration was 18 months. Serum levels of total cholesterol, LDL, HDL, hs-CRP, CEA, CA15-3, CK, SGPT, LDH, and creatinine were monitored, and the status of ER, PR, and Her2 receptors was determined. A cutoff value of > 10 mg/l was used to categorize patients into high vs. low hs-CRP. Primary endpoints were response rate (RR) and toxicity, and secondary endpoint was survival. Statistical analysis of data was performed using Prism Graphpad, version 5. Results: Eighty Two patients met the inclusion criteria and consented. The mean age was 47.3 ± 9.85 years. Seventy Seven patients were assessable. The response rates were 35% and 32.5%, whereas progression rates were 35% and 37.5% in simvastatin and placebo groups respectively (p >0.05 for all comparisons). The median survival was 15 months in the simvastatin group and 17 months in the placebo group (P = 0.47, HR = 1.248, 95% CI (0.6863-2.268)).The median survival was 9 months vs. undefined (p = 0.0014, HR = 2.73, 95% CI (1.476–5.05)), and survival rates were 28.09% versus 56.72% in patients with high vs. normal baseline hs-crp levels, respectively regardless of the treatment subgroup. Conclusions: Our data prove a safe profile but nota chemo-sensitizing effect of simvastatin at 40 mg per day in patients with MBC, and also suggest a clinical utility of baseline hs-CRP as a useful prognostic tool in MBC patients. Disclosure: All authors have declared no conflicts of interest.