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M. Szczyrek



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    OA 08 - Neuroendocrine Carcinoma: Translational (ID 667)

    • Event: WCLC 2017
    • Type: Oral
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      OA 08.03 - Effect of TOP2A and ERCC1 Genes Polymorphism on the Efficacy and Toxicity of Cisplatin and Etoposide Therapy in SCLC Patients (ID 8367)

      11:20 - 11:30  |  Author(s): M. Szczyrek

      • Abstract
      • Presentation
      • Slides

      Background:
      Small cell lung cancer (SCLC) shows an aggressive course with early metastases to distant organs. The main treatment regimen for SCLC patients involves platinum based chemotherapy (cisplatin or carboplatin) and etoposide. Genetic alternations, as single-nucleotide polymorphisms (SNPs) in TOP2A (topoisomerase II alpha) and in ERCC1 (endonuclease non-catalytic subunit) genes, were tested as a prognostic and predictive factors in patients with non-small cell lung cancer (NSCLC) treated with chemotherapy. However, there is limited data about clinical relevance of these genetic alternations in SCLC. Therefore, we undertook the present retrospective study to determine the influence of SNPs in TOP2A (rs34300454; rs13695; rs11540720) and ERCC1 (rs11615; rs3212986) genes on efficiency and toxicity of chemotherapy with platinum and etoposide in patients with SCLC.

      Method:
      The studied group included 103 Caucasian SCLC patients (65 male, 38 female, median age 65 ± 7,5 years). We collected detailed clinical-demographical data including: smoking history, environmental/occupational exposure to carcinogens, performance status, disease stage, and the presence of distant metastases. The response to the treatment was carefully monitored according to RECIST criteria, as well as side effects as anemia, neutropenia or weight loss were noted. For SNPs genotyping, we used DNA isolated from peripheral blood leukocytes using Qiamp DNA Mini Kit (Qiagen, Germany) and TaqMan hydrolyzing probes (Applied Biosystem, USA) in real-time PCR technique on Eco Illumina (Illumina, USA) device.

      Result:
      Patients with C/C genotype in rs13695 of TOP2A gene had significantly lower risk of neutropenia during chemotherapy than C/T heterozygous patients (p=0,01894; χ²=5.51; OR=2,676; 95% CI=1,165-6,143). Patients harbouring homozygous C/C genotype in rs3212986 of ERCC1 gene had significantly higher risk of anaemia during chemotherapy than heterozygous C/A patients (p=0,04531; χ²=4,01; OR=0,417; 95% CI=0,175-0,991). Furthermore, homozygous A/A genotype in rs11615 of ERCC1 gene was associated with significant prolongation of overall survival (12 vs. 9 months) compared to heterozygous G/A genotype of this gene (p=0,0120; χ²=6,3063; HR=1,657; 95% CI=1,0710-2,5633).

      Conclusion:
      SNPs in ERCC1 and TOP2 genes are associated with the toxicities and overall survival of SCLC patients treated with platinum and etoposide based chemotherapy.

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