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Chemotherapy-induced neutropenia does not correlate with DNA repair gene polymorphisms and treatment efficacy in advanced non-small-cell lung cancer patients

By Rafael Sirera Pérez


[EN] Background: Platinum doublets are standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to assess whether neutropenia is: (1) an indicator for treatment efficacy, or (2) associated with specific polymorphisms. Patients and Methods: Four hundred ninety-four patients, treated with cisplatin-docetaxel were retrospectively analyzed. Relative dose intensity (RDI) was assessed for both drugs. Neutrophil counts were assessed only on Day 21 of each cycle. Genotyping was performed for 4 different polymorphisms in ERCC1, XRCC3, XPD-23, and XPD-10. Results: The median overall survival was 9 months. The mean RDI was 0.94 for cisplatin and 0.93 for docetaxel. Four hundred three patients received ¿ 3 cycles of chemotherapy, and 239 received ¿ 6 cycles. Thirty-one percent developed neutropenia, and 19% had Grade (G)3-4 neutropenia. RDI was lower in patients with neutropenia (G1-4; 0.87-0.93) when compared with those without (G0; 0.94-0.95; P <.02). Male patients (P =.02) had inferior survival when compared with female patients, and ECOG (Eastern Cooperative Oncology Group) 1-2 patients (P <.001) had worse survival when compared with ECOG 0. There was no significant survival difference with respect to Grade of neutropenia (G0, 8.7 vs. G1-2, 11.6 vs. G3-4, 9.6 months; P =.41). In ECOG 0 patients, survival was significantly better for neutropenic G1-4 (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.31-0.96; P =.034) when compared with non-neutropenic (G0) patients. No association was observed between examined polymorphisms and neutropenia. Conclusion: RDI was significantly higher in patients who did not develop neutropenia during treatment, but as the nadir period was not explored in our study, the low occurrence of neutropenia in our cohort is considered underestimated. There was no significant survival difference with respect to grade of neutropenia. Finally, none of the examined single nucleotide polymorphisms (SNPs) were associated with the presence of neutropenia, disease characteristics, response rates, or survival. © 2011 Elsevier Inc. All rights reserved.Sirera Pérez, R. (2011). Chemotherapy-induced neutropenia does not correlate with DNA repair gene polymorphisms and treatment efficacy in advanced non-small-cell lung cancer patients. Clinical Lung Cancer. 12(4):224-230. doi:10.1016/j.cllc.2011.03.023S22423012

Topics: Advanced disease, Chemotherapy, Efficacy to therapy, NSCLC, SNP, Cisplatin, Docetaxel, Excision repair cross complementing protein 1, Unclassified drug, Xeroderma pigmentosum group D protein, Xeroderma pigmentosum group D protein 10, Xeroderma pigmentosum group D protein 23, XRCC3 protein, Advanced cancer, Article, Cancer combination chemotherapy, Chemotherapy induced neutropenia, DNA repair, Drug dose reduction, Drug dose regimen, Drug efficacy, Drug induced disease, Gene frequency, Human, Lung non small cell cancer, Multiple cycle treatment, Neutropenia, Overall survival, Prognosis, Sex difference, Single nucleotide polymorphism, Treatment response, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Large Cell, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, DNA-Binding Proteins, Endonucleases, Female, Follow-Up Studies, Humans, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Polymorphism, Genetic, Retrospective Studies, Survival Rate, Taxoids, Treatment Outcome, MICROBIOLOGIA
Publisher: 'Elsevier BV'
Year: 2011
DOI identifier: 10.1016/j.cllc.2011.03.023
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Provided by: RiuNet
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