• 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, and Won Ki Kang.
• Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
• Eur. J. Cancer. 2014 Nov 1; 50 (16): 2822-30.

PurposeWe 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).MethodsIn 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 1000mg/m(2) twice daily for 14 days and cisplatin 80 mg/m(2) 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.ResultsBetween 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.ConclusionsAddition 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.Copyright © 2014 Elsevier Ltd. All rights reserved.

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