Chemotherapy with platinum compounds and gemcitabine is frequently used in first-line treatment of advanced non-small cell lung cancer (NSCLC) patients in which tyrosine kinase inhibitors (EGFR or ALK) cannot be administered. Unfortunately, less than half of the patients achieve the benefit from chemotherapy. Gemcitabine is an analog of deoxycytidine (pyrimidine antimetabolite) with antitumor activity. The excess of deoxycytidine synthesized by RRM1 enzyme activity may be a cause of competitive displacement of gemcitabine, which reduces the efficacy of this cytostatic. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) of the RRM1 promoter (−37C>A, −524C>T) and the effectiveness of first-line chemotherapy based on platinum compounds and gemcitabine in NSCLC patients.
SNPs were determined by SNaPshot PCR® in DNA isolated from peripheral blood of 91 NSCLC patients.
The median progression-free survival (PFS) was significantly longer in carriers of AA (−37C>A) as well as CC (−524C>T) genotype of RRM1 compared to patients with other genotypes (10.5 vs 3.5 months, p = 0.0437; HR = 2.17, 95 % CI 1.02–4.62 and 10.5 vs 3.5 months, p = 0.0343; HR = 2.12, 95 % CI 1.06–4.27). In addition, the CC genotype carriers (−37C>A) showed a significant increase in the risk of shortening overall survival (OS) in comparison to patients with AA or AC genotypes (9.5 vs 18 months, p = 0.0193; HR = 2.13, 95 % CI 1.13–4.03).
Presence of rare AA (−37C>A) and CC (−524C>T) genotypes of the RRM1 may be favorable predictive factors for chemotherapy with platinum compounds and gemcitabine in NSCLC patients.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ®) Non-Small Cell Lung Cancer version 1.2015 (2015) http://www.nccn.org. Accessed 25 June 2015.
Gridelli C, de Marinis F, Cappuzzo F, Di Maio M, Hirsch FR, Mok T, et al. Treatment of advanced non-small-cell lung cancer with epidermal growth factor receptor (EGFR) mutation or ALK gene rearrangement: results of an international expert panel meeting of the Italian Association of Thoracic Oncology. Clin Lung Cancer. 2014;15:173–81. CrossRefPubMed
Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012;13(3):239–46. CrossRefPubMed
Krawczyk P, Ramlau R, Chorostowska-Wynimko J, Powrózek T, Lewandowska MA, Limon J, et al. The efficacy of EGFR gene mutation testing in various samples from non-small cell lung cancer patients: a multicenter retrospective study. J Cancer Res Clin Oncol. 2015;141(1):61–8. doi: 10.1007/s00432-014-1789-x. CrossRefPubMed
Deng JH, Deng J, Shi DH, Ouyang XN, Niu PG. Clinical outcome of cisplatin-based chemotherapy is associated with the polymorphisms of GSTP1 and XRCC1 in advanced non-small cell lung cancer patients. Clin Transl Oncol. 2015 (Epub ahead of print).
Lin L, Liu X, Song S, Wang S. A study on the relationship between RRM1 single nucleotide polymorphisms and clinical characteristics in lung cancer patients. Zhongguo Fei Ai Za Zhi. 2008;11(6):784–8. PubMed
Mlak R, Krawczyk P, Ramlau R, Kalinka-Warzocha E, Wasylecka-Morawiec M, Wojas-Krawczyk K, et al. Predictive value of ERCC1 and RRM1 gene single-nucleotide polymorphisms for first-line platinum- and gemcitabine-based chemotherapy in non-small cell lung cancer patients. Oncol Rep. 2013;30(5):2385–98. PubMed
Ludovini V, Floriani I, Pistola L, Minotti V, Meacci M, Chiari R, et al. Association of cytidine deaminase and xeroderma pigmentosum group D polymorphisms with response, toxicity, and survival in cisplatin/gemcitabine-treated advanced non-small cell lung cancer patients. J Thorac Oncol. 2011;6(12):2018–26. CrossRefPubMed
- The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient
- Springer International Publishing
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