Effect of and gene polymorphisms on the efficacy and toxicity of cisplatin and etoposide-based chemotherapy in small cell lung cancer patients.

INTRODUCTION

The main treatment regimen for small cell lung cancer (SCLC) involves platinum-based chemotherapy (cisplatin or carboplatin) and etoposide. Single nucleotide polymorphisms (SNPs) in and genes were tested as prognostic and predictive factors in non-small cell lung cancer (NSCLC). There are limited data about the clinical relevance of these genetic alterations in SCLC. We undertook this retrospective study to determine the influence of SNPs in (rs34300454; rs13695; rs11540720) and (rs11615; rs3212986) genes on the efficiency and toxicity of chemotherapy with platinum and etoposide in SCLC Caucasian patients.

MATERIAL AND METHODS

The studied group included 103 Caucasian SCLC patients (65 male, 38 female, median age 65 ±7.5 years). Detailed clinical-demographical data were collected and response to treatment was monitored. DNA was isolated from peripheral blood leukocytes using QIAamp DNA Mini Kit. Single nucleotide polymorphisms were analyzed using TaqMan hydrolyzing probes in real-time PCR technique on an Eco Illumina device.

RESULTS

Patients with C/C genotype in rs13695 of the gene had significantly lower risk of neutropenia during chemotherapy than C/T heterozygous patients ( = 0.02, χ² = 5.51, OR = 2.676, 95% CI: 1.165-6.143). Patients harbouring homozygous C/C genotype in rs3212986 of the gene had significantly higher risk of anaemia during chemotherapy, than heterozygous C/A patients ( = 0.045, χ² = 4.01, OR = 0.417, 95% CI: 0.175-0.991). Furthermore, heterozygous G/A genotype in rs11615 of the gene was associated with significant shortening of OS (9 vs. 12 months) compared to homozygous A/A genotype ( = 0.01, χ² = 6.31, HR = 1.657, 95% CI: 1.0710-2.5633).

CONCLUSIONS

SNPs in and genes may be associated with the toxicities and survival of SCLC patients treated with cisplatin and etoposide.