Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: A double-blind randomised phase 3 study

Seung Tae Kim, Jung Hun Kang, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, In Gyu Hwang, Sang Cheol Lee, Keon Woo Park, Hyo Rak Lee, Won Ki Kang

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Purpose We aimed to the addition of synthetic 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitor, simvastatin to capecitabine-cisplatin (XP) in patients with previously untreated advanced gastric cancer (AGC). Methods In this double-blind, placebo-controlled, phase III study, we enrolled patients aged 18 years or older with histological or cytological confirmed metastatic adenocarcinoma of the stomach or gastroesophageal junction (GEJ) at nine centres in Korea. Patients, stratified by disease measurability and participating site, were randomly assigned (1:1) to receive capecitabine 1000 mg/m2 twice daily for 14 days and cisplatin 80 mg/m2 on day 1 every 3 weeks plus either simvastatin 40 mg or placebo, once daily. Cisplatin was given for 8 cycles; capecitabine and simvastatin were administered until disease progression or unacceptable toxicities. This study is registered with ClinicalTrials.gov, number NCT01099085. Results Between February 2009 and November 2012, 244 patients were enrolled and assigned to treatment groups (120 simvastatin, 124 placebo). Median progression free survival (PFS) for 120 patients allocated XP plus simvastatin was 5.2 months (95% confidence interval (CI) 4.3-6.1) compared with 4.63 months (95% CI 3.5-5.7) for 124 patients who were allocated to XP plus placebo (hazard ratio 0.930, 95% CI 0.684-1.264; p = 0.642). 63 (52.5%) of 120 patients in simvastatin group and 70 (56.4%) of 124 had grade 3 or higher adverse events. Conclusions Addition of 40 mg simvastatin to XP does not increase PFS in our trial, although it does not increase toxicity. Low dose of simvastatin (40 mg) to chemotherapy is not recommended in untargeted population with AGC.

Original languageEnglish
Pages (from-to)2822-2830
Number of pages9
JournalEuropean Journal of Cancer
Volume50
Issue number16
DOIs
StatePublished - Nov 2014
Externally publishedYes

Keywords

  • A (HMG-CoA)
  • Gastric cancer
  • Simvastatin
  • Synthetic 3-hydroxy-3-methyglutaryl coenzyme

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