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

Vienna Ludovini, Irene Floriani, Lorenza Pistola, Vincenzo Minotti, Marialuisa Meacci, Rita Chiari, Daniela Garavaglia, Francesca Romana Tofanetti, Antonella Flacco, Annamaria Siggillino, Elisa Baldelli, Maurizio Tonato, Lucio Crinò

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)2018-2026
Number of pages9
JournalJournal of Thoracic Oncology
Volume6
Issue number12
DOIs
Publication statusPublished - Dec 2011

Fingerprint

gemcitabine
Cytidine Deaminase
Xeroderma Pigmentosum
Non-Small Cell Lung Carcinoma
Cisplatin
Survival
Genotype
Disease-Free Survival
Drug Therapy
Computer Systems
Therapeutics
Proportional Hazards Models
Pharmaceutical Preparations
Genes
Single Nucleotide Polymorphism
Real-Time Polymerase Chain Reaction
DNA

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 journalArticle

Ludovini, V, Floriani, I, Pistola, L, Minotti, V, Meacci, M, Chiari, R, Garavaglia, D, Tofanetti, FR, Flacco, A, Siggillino, A, Baldelli, E, Tonato, M & Crinò, L 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', Journal of Thoracic Oncology, vol. 6, no. 12, pp. 2018-2026. https://doi.org/10.1097/JTO.0b013e3182307e1f
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. / 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. In: Journal of Thoracic Oncology. 2011 ; Vol. 6, No. 12. pp. 2018-2026.
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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.",
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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

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