Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 2018-2026 |
| Number of pages | 9 |
| Journal | Journal of Thoracic Oncology |
| Volume | 6 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2011 |
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Keywords
- Advanced NSCLC
- Polymorphisms
- Response to chemotherapy
- Survival
- Toxicity
ASJC Scopus subject areas
- Oncology
- Pulmonary and Respiratory Medicine
Cite this
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. / 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.
In: Journal of Thoracic Oncology, Vol. 6, No. 12, 12.2011, p. 2018-2026.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Ludovini, Vienna
AU - Floriani, Irene
AU - Pistola, Lorenza
AU - Minotti, Vincenzo
AU - Meacci, Marialuisa
AU - Chiari, Rita
AU - Garavaglia, Daniela
AU - Tofanetti, Francesca Romana
AU - Flacco, Antonella
AU - Siggillino, Annamaria
AU - Baldelli, Elisa
AU - Tonato, Maurizio
AU - Crinò, Lucio
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Advanced NSCLC
KW - Polymorphisms
KW - Response to chemotherapy
KW - Survival
KW - Toxicity
UR - http://www.scopus.com/inward/record.url?scp=81755185463&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81755185463&partnerID=8YFLogxK
U2 - 10.1097/JTO.0b013e3182307e1f
DO - 10.1097/JTO.0b013e3182307e1f
M3 - Article
C2 - 22052224
AN - SCOPUS:81755185463
VL - 6
SP - 2018
EP - 2026
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 12
ER -