Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2011
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.
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Ludovini Vienna, Floriani Irene, Pistola Lorenza, Minotti Vincenzo, Meacci Marialuisa, Chiari Rita, Garavaglia Daniela, Tofanetti Francesca Romana, Flacco Antonella, Siggillino Annamaria, Baldelli Elisa, Tonato Maurizio, Crinò Lucio
Аннотация
BACKGROUND: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non-small cell lung cancer (NSCLC). Genetic variations in drug metabolism may affect the clinical response, toxicity, and prognosis of NSCLC patients treated with cisplatin/gemcitabine-based therapy.
PATIENTS AND METHODS: We evaluated seven single-nucleotide polymorphisms of six genes CDA Lys27Gln (A/C); CDA C435T; ERCC1 C118T; XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); P53 Arg72Pro (G/C), and RRM1 C524T in 192 chemotherapy-naive patients with advanced NSCLC treated with cisplatin/gemcitabine-based regimen by TaqMan probe-based assays with 7300 Real-Time PCR System, using genomic DNA extracted from blood samples.
RESULTS: The CDA 435 T/T genotype was significantly associated with better response (p = 0.03). The CDA 435 C/T genotype was associated with a significantly increased risk of nonhematological toxicity of grade ≥3 (p = 0.02) after adjusting for performance status, age, and type of treatment regimen. In the multivariate Cox model, the XPD 751 C/C genotype was a significant prognostic factor of longer progression-free survival (p = 0.006).
CONCLUSION: Our data suggest polymorphic variations of drug metabolic gene were associated with response and toxicity of cisplatin/gemcitabine-based therapy and progression-free survival of patients with advanced NSCLC.
PATIENTS AND METHODS: We evaluated seven single-nucleotide polymorphisms of six genes CDA Lys27Gln (A/C); CDA C435T; ERCC1 C118T; XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); P53 Arg72Pro (G/C), and RRM1 C524T in 192 chemotherapy-naive patients with advanced NSCLC treated with cisplatin/gemcitabine-based regimen by TaqMan probe-based assays with 7300 Real-Time PCR System, using genomic DNA extracted from blood samples.
RESULTS: The CDA 435 T/T genotype was significantly associated with better response (p = 0.03). The CDA 435 C/T genotype was associated with a significantly increased risk of nonhematological toxicity of grade ≥3 (p = 0.02) after adjusting for performance status, age, and type of treatment regimen. In the multivariate Cox model, the XPD 751 C/C genotype was a significant prognostic factor of longer progression-free survival (p = 0.006).
CONCLUSION: Our data suggest polymorphic variations of drug metabolic gene were associated with response and toxicity of cisplatin/gemcitabine-based therapy and progression-free survival of patients with advanced NSCLC.
Предметные рубрики MeSH
AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCisplatinCytidine DeaminaseDeoxycytidineDisease-Free SurvivalFemaleGenotypeHumansLung NeoplasmsMaleMiddle AgedPolymorphism, Single NucleotideProportional Hazards ModelsRetrospective StudiesXeroderma Pigmentosum Group D ProteinGemcitabine