390P - A prospective, randomized, placebo controlled study of simvastatin/chemotherapy effectiveness in metastatic breast cancer patients

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer agents
Breast Cancer
Therapy
Biological therapy
Presenter Lama Youssef
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors L.A. Youssef1, H. Alarfi2, M.I. Salamoon3, M. Kadri4, M. Alammar4, M.A. Haykal4, A. Alseoudi4
  • 1Pharmaceutics & Pharmaceutical Technology, University of Damascus, N/A - Damascus/SY
  • 2Pharamceutics & Pharmaceutical Technology, University of Damascus, Damascus/SY
  • 3Medical Oncology, al Bairouni university hospital, Damascus/SY
  • 4Medical Oncology, AlBaironi Hospital, Damascus/SY

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.