Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients

Jung Yong Hong, Eun Mi Nam, Jeeyun Lee, Joon Oh Park, Sang Cheol Lee, Seo Young Song, Seong Ho Choi, Jin Seok Heo, Se Hoon Park, Ho Yeong Lim, Won Ki Kang, Young Suk Park

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Background: Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer. Methods: Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP). Results: Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7-4.1 months) and 3.6 months (95 % CI 3.1-4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2-33.8 %) and 57.1 % (95 % CI 19.8-44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis. Conclusions: Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.

Original languageEnglish
Pages (from-to)125-130
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume73
Issue number1
DOIs
StatePublished - Jan 2014

Keywords

  • Chemotherapy
  • Gemcitabine
  • Pancreatic cancer
  • Simvastatin

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