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
| Autor: | Annamaria Siggillino, Daniela Garavaglia, A. Flacco, Vincenzo Minotti, Lorenza Pistola, Lucio Crinò, M. Meacci, Irene Floriani, Maurizio Tonato, Vienna Ludovini, Francesca Romana Tofanetti, Elisa Baldelli, Rita Chiari |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Oncology
Adult Male Pulmonary and Respiratory Medicine medicine.medical_specialty Lung Neoplasms Survival Genotype medicine.medical_treatment Deoxycytidine Polymorphism Single Nucleotide Disease-Free Survival Internal medicine Carcinoma Non-Small-Cell Lung Cytidine Deaminase Response to chemotherapy Antineoplastic Combined Chemotherapy Protocols medicine Humans Lung cancer Aged Proportional Hazards Models Retrospective Studies Xeroderma Pigmentosum Group D Protein Cisplatin Aged 80 and over Chemotherapy Performance status Toxicity business.industry Middle Aged medicine.disease Gemcitabine Regimen Advanced NSCLC Female ERCC1 business Polymorphisms medicine.drug |
| Zdroj: | Journal of Thoracic Oncology. 6(12):2018-2026 |
| ISSN: | 1556-0864 |
| DOI: | 10.1097/jto.0b013e3182307e1f |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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