title: Chemotherapy-induced neutropenia does not correlate with DNA repair gene polymorphisms and treatment efficacy in advanced non-small-cell lung cancer patients.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Servicio de Oncología Médica, Hospital General Universitario, Valencia, Spain.
authors: Vega
authors: V
authors: Iranzo
authors: Rafael
authors: R
authors: Sirera
authors: Roy M
authors: RM
authors: Bremnes
authors: Ana
authors: A
authors: Blasco
authors: Eloísa
authors: E
authors: Jantus-Lewintre
authors: Miquel
authors: M
authors: Tarón
authors: Alfonso
authors: A
authors: Berrocal
authors: Sara
authors: S
authors: Blasco
authors: Cristina
authors: C
authors: Caballero
authors: Nieves
authors: N
authors: Del Pozo
authors: Rafael
authors: R
authors: Rosell
authors: Carlos
authors: C
authors: Camps
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D000077143:Docetaxel; D004720:Endonucleases / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced* / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D043823:Taxoids; C110901:X-ray repair cross complementing protein 3; D000077143:Docetaxel; C071447:ERCC1 protein, human; D004720:Endonucleases; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin