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/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) 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.
RCT Entities:
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/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) 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.
Authors: Bechien U Wu; Jonathan Chang; Christie Y Jeon; Stephen J Pandol; Brian Huang; Eunis W Ngor; Andrew L Difronzo; Robert M Cooper Journal: Am J Gastroenterol Date: 2015-07-21 Impact factor: 10.864
Authors: Linara Gabitova-Cornell; Aizhan Surumbayeva; Suraj Peri; Janusz Franco-Barraza; Diana Restifo; Nicole Weitz; Charline Ogier; Aaron R Goldman; Tiffiney R Hartman; Ralph Francescone; Yinfei Tan; Emmanuelle Nicolas; Neelima Shah; Elizabeth A Handorf; Kathy Q Cai; Alana M O'Reilly; Ido Sloma; Rachel Chiaverelli; Richard A Moffitt; Vladimir Khazak; Carolyn Y Fang; Erica A Golemis; Edna Cukierman; Igor Astsaturov Journal: Cancer Cell Date: 2020-09-24 Impact factor: 31.743
Authors: Tatiana Y Hargrove; Laura Friggeri; Zdzislaw Wawrzak; Suneethi Sivakumaran; Eugenia M Yazlovitskaya; Scott W Hiebert; F Peter Guengerich; Michael R Waterman; Galina I Lepesheva Journal: J Lipid Res Date: 2016-06-16 Impact factor: 5.922
Authors: Tsuyoshi Hamada; Natalia Khalaf; Chen Yuan; Vicente Morales-Oyarvide; Ana Babic; Jonathan A Nowak; Zhi Rong Qian; Kimmie Ng; Douglas A Rubinson; Peter Kraft; Edward L Giovannucci; Meir J Stampfer; Charles S Fuchs; Shuji Ogino; Brian M Wolpin Journal: Clin Gastroenterol Hepatol Date: 2018-02-21 Impact factor: 11.382