Single nucleotide polymorphisms in MDR1 gen correlates with outcome in advanced non-small-cell lung cancer patients

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N Viñolas1, M Provencio, N Reguart

  • 1Hospital Clinic de Barcelona, IDIBAPS, Barcelona, Spain. nvinolas@clinic.ub.es

Lung Cancer (Amsterdam, Netherlands)
|July 15, 2010
PubMed
Abstract

Insights

Genetic variations in the MDR1 gene, specifically the 3435 CC genotype, are linked to better outcomes in non-small cell lung cancer (NSCLC) patients treated with chemotherapy. Younger age and good performance status also improved progression-free survival.

Area of Science:

  • Oncology
  • Pharmacogenetics
  • Genetics

Background:

  • Chemosensitivity in non-small cell lung cancer (NSCLC) can be influenced by genetic abnormalities.
  • Investigating genetic polymorphisms may reveal new therapeutic targets for NSCLC.

Purpose of the Study:

  • To assess the impact of polymorphisms in ERCC1, XPD, RRM1, and MDR1 genes on the efficacy and tolerability of cisplatin and vinorelbine chemotherapy in NSCLC patients.
  • To identify genetic markers that predict treatment response and survival in NSCLC.

Main Methods:

  • A cohort of 94 previously untreated stage IV or IIIB NSCLC patients with WHO performance status 0-1 were enrolled.
  • Patients received intravenous vinorelbine and cisplatin chemotherapy for a maximum of eight cycles.
  • Multivariate analysis was used to identify prognostic factors for time to progression and survival.

Main Results:

  • The median number of cycles administered was 6, with an overall median survival of 10.92 months and median time to progression of 5.89 months.
  • MDR1 3435 CC genotype, ECOG performance status 0, and younger age were significant prognostic factors for a lower risk of progression.
  • ECOG performance status 0 was the only significant prognostic factor for survival.

Conclusions:

  • The MDR1 3435 CC genotype is a key predictor of a lower risk of progression in NSCLC patients treated with cisplatin and vinorelbine.
  • Performance status and age are also important prognostic factors influencing treatment outcomes in NSCLC.
  • No significant association was found between the analyzed single nucleotide polymorphisms (SNPs) and the toxicity of vinorelbine and cisplatin chemotherapy.

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