Concomitant Statin Use Has a Favorable Effect on Gemcitabine-Erlotinib Combination Chemotherapy for Advanced Pancreatic Cancer
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Purpose: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreaticcancer. This study aimed to determine the clinical factors associated with response to this treatment. Materials and Methods: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cyclesof gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. “Long-term response”was defined as tumor stabilization after >6 chemotherapy cycles. Results: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariateanalysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history ofstatin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. Onmultivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognosticfactors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statintreatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidenceinterval, 0.26–0.92; p=0.026). Conclusion: These results suggest that statins have a favorable effect on “long-term response” to gemcitabine-erlotinib chemotherapyin unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.
Abstract
Purpose: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreaticcancer. This study aimed to determine the clinical factors associated with response to this treatment. Materials and Methods: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cyclesof gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. “Long-term response”was defined as tumor stabilization after >6 chemotherapy cycles. Results: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariateanalysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history ofstatin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. Onmultivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognosticfactors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statintreatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidenceinterval, 0.26–0.92; p=0.026). Conclusion: These results suggest that statins have a favorable effect on “long-term response” to gemcitabine-erlotinib chemotherapyin unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.
참고문헌 (36)
- Jemal A, "Cancer statistics, 2010", CA Cancer J Clin, 60, pp.277~300 (2010)
- Kelly DM, "Pancreatic carcinoma", Ann Oncol, 6, pp.19~28 (1995)
- Burris HA 3rd, "Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial", J Clin Oncol, 15, pp.2403~2413 (1997)
- Conroy T, "FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer", N Engl J Med, 364, pp.1817~1825 (2011)
- Von Hoff DD, "Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine", N Engl J Med, 369, pp.1691~1703 (2013)
- Moore MJ, "Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group", J Clin Oncol, 25, pp.1960~1966 (2007)
- Linardou H, "Assessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced nonsmall-cell lung cancer and metastatic colorectal cancer", Lancet Oncol, 9, pp.962~972 (2008)
- Murray S, "Somatic mutations of the tyrosine kinase domain of epidermal growth factor receptor and tyrosine kinase inhibitor response to TKIs in non-small cell lung cancer: an analytical database", J Thorac Oncol, 3, pp.832~839 (2008)
- 서용성, "Impact of Statin Treatment on Strut Coverage after Drug-Eluting Stent Implantation", Yonsei Medical Journal, 56(1), pp.45~52 (2015), 연세대학교의과대학[DOI]
- Nielsen SF, "Statin use and reduced cancer-related mortality", N Engl J Med, 367, pp.1792~1802 (2012)
- Chan KK, "The statins as anticancer agents", Clin Cancer Res, 9, pp.10~19 (2003)
- Dimitroulakos J, "Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas", wNeoplasia, 4, pp.337~346 (2002)
- Jakobisiak M, "Potential antitumor effects of statins (Review)", Int J Oncol, 23, pp.1055~1069 (2003)
- Park HJ, "3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA", Circ Res, 91, pp.143~150 (2002)
- Lee J, "Lovastatin-induced RhoA modulation and its effect on senescence in prostate cancer cells", Biochem Biophys Res Commun, 339, pp.748~754 (2006)
- Park C, "Lovastatin-induced E2F-1 modulation and its effect on prostate cancer cell death", Carcinogenesis, 22, pp.1727~1731 (2001)
- Winiarska M, "Statins impair antitumor effects of rituximab by inducing conformational changes of CD20", PLoS Med, 5, pp.e64~ (2008)
- Wertheimer AI, "The defined daily dose system (DDD) for drug utilization review", Hosp Pharm, 21, pp.233~234 (1986)
- Broughton T, "Statin use is associated with a reduced incidence of colorectal adenomatous polyps", Int J Colorectal Dis, 28, pp.469~476 (2013)
- Hoffmeister M, "Individual and joint use of statins and low-dose aspirin and risk of colorectal cancer: a population-based case-control study", Int J Cancer, 121, pp.1325~1330 (2007)
- Poynter JN, "Rennert HS, et al. Statins and the risk of colorectal cancer", N Engl J Med, 352, pp.2184~2192 (2005)
- Robertson DJ, "Neither long-term statin use nor atherosclerotic disease is associated with risk of colorectal cancer", Clin Gastroenterol Hepatol, 8, pp.1056~1061 (2010)
- Samadder NJ, "Risk of colorectal cancer in self-reported inflammatory bowel disease and modification of risk by statin and NSAID use", Cancer, 117, pp.1640~1648 (2011)
- Simon MS, "Prospective analysis of association between use of statins or other lipid-lowering agents and colorectal cancer risk", Ann Epidemiol, 22, pp.17~27 (2012)
- Khurana V, "Statins reduce the risk of pancreatic cancer in humans: a case-control study of half a million veterans", Pancreas, 34, pp.260~265 (2007)
- Goldstein JL, "Regulation of the mevalonate pathway", Nature, 343, pp.425~430 (1990)
- Pruitt K, "Ras and Rho regulation of the cell cycle and oncogenesis", Cancer Lett, 171, pp.1~10 (2001)
- Seabra MC, "Rab GTPases, intracellular traffic and disease", Trends Mol Med, 8, pp.23~30 (2002)
- Kusama T, "3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis", Gastroenterology, 122, pp.308~317 (2002)
- Hong JY, "Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients", Cancer Chemother Pharmacol, 73, pp.125~130 (2014)
- Carlberg M, "Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth", J Biol Chem, 271, pp.17453~17462 (1996)
- Gschwind A, "Cell communication networks: epidermal growth factor receptor transactivation as the paradigm for interreceptor signal transmission", Oncogene, 20, pp.1594~1600 (2001)
- Gibbs JB, "Farnesyltransferase inhibitors: Ras research yields a potential cancer therapeutic", Cell, 77, pp.175~178 (1994)
- Mantha AJ, "Targeting the mevalonate pathway inhibits the function of the epidermal growth factor receptor", Clin Cancer Res, 11, pp.2398~2407 (2005)
- Hezel AF, "Genetics and biology of pancreatic ductal adenocarcinoma", Genes Dev, 20, pp.1218~1249 (2006)
- Lee J, "Effect of simvastatin on cetuximab resistance in human colorectal cancer with KRAS mutations", J Natl Cancer Inst, 103, pp.674~688 (2011)
