Correlation of polymorphisms of genes involved in platinum/gemcitabine (P/G)-based metabolism with toxicity and clinical response in patients (pts) with advanced non-small cell lung cancer (NSCLC)
| Autor: | Vienna Ludovini, Maurizio Tonato, Rita Chiari, Irene Floriani, L. Crinò, M. Ferraldeschi, Lorenza Pistola, A. Flacco, D. Garavaglia, Francesca Romana Tofanetti, M. Meacci |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 27:8093-8093 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 8093 Background: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in NSCLC. Genetic variations in drugs metabolism may affect the clinical response, toxicity and prognosis of NSCLC pts treated with P/G-based therapy. Methods: We evaluated 8 single nucleotide polymorphisms (SNPs) of 6 genes (P53 Arg72Pro (G/C); XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); ERCC1 Asn118Asn (C/T); CDA Lys27Gln (A/C), Ala70Thr (G/A), Thr145Thr (C/T) and RRM1 C524T) involved in P/G-based metabolism in a homogeneous population of pts with advanced NSCLC treated with this regime. Genomic DNA was extracted from whole blood samples using the QIAamp DNA estraction kit on Biorobot EZ1 (Qiagen). Polymorphisms were detected with TaqMan-probe based assays using the 7300 Real-Time PCR System (Applied Biosystems, Foster City, CA). Association between SNPs and response, toxicity, progression free survival and overall survival was estimated using logistic regression model, the Kaplan-Meier method, the long-rank test and the Cox proportional hazard model. Results: We performed a retrospective analysis in 192 chemotherapy-naive pts (median age 63 years), including M/F:74/26%; stage IIIb/IV:24/76%; Adeno/Squa/other Ca:42/27/31%; ECOG PS:0–1/2–3:94/6%. Overall response rate was 32.3%, stable disease 25% and disease progression 42.7%. The CDA Thr145Thr T/T genotype significantly correlated with poorer response (partial response in 23.1% of pts versus 42.3% and 34.6% in C/T and C/C genotypes, respectively; p=0.03). The ERCC1 T/T genotype was significantly associated with haematological toxicity (G1–4) (p=0.05) compared to ERCC1 C/C allele. The CDA Thr145Thr C/T genotype was significantly associated with non-haematological toxicity (G3–4) (p=0.02) compared to CDA Thr145Thr C/C allele. The median overall survival (OS) time and progression free survival (PFS) were 12.7 and 4.7 months, respectively. None of the analyzed polymorphisms was related to PFS or OS. Conclusions: These data suggest that genetic polymorphisms in the ERCC1 and CDA genes may modulate the toxicity and response to P/G-based therapy in pts with advanced NSCLC. No significant financial relationships to disclose. |
| Databáze: | OpenAIRE |
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