A prospective study of biomarker-guided chemotherapy in patients with non-small cell lung cancer

Cancer Chemother Pharmacol. 2014 Oct;74(4):839-46. doi: 10.1007/s00280-014-2513-x. Epub 2014 Aug 14.

Abstract

Purpose: To assess the therapeutic value of biomarker-guided chemotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Methods: Eighty-five NSCLC patients at stage IIIb or IV were divided into two groups based on the feasibility of biomarker analysis. Group A included patients with biomarker data (n = 41); Group B were patients without biomarker results (n = 44). Tumor samples obtained by fiberoptic bronchoscopy and computerized tomography-guided needle biopsy were analyzed by immunohistochemistry for intratumoral level of excision repair cross-complementing gene 1 (ERCC1), ribonucleotide reductase M1 (RRM1), and β-tubulin III. Chemotherapy regimens in Group A were determined according to the status of molecular signatures, whereas a standard gemcitabine plus cisplatin regimen was used for Group B. Tumor response, patient survival, and adverse effects were monitored for both groups.

Results: The overall response rate, defined as complete response plus partial response, was 56.1% for Group A, significantly higher than that in Group B (31.8%; P = 0.024). The median progression-free survival (PFS) time was 5.2 months for Group A, significantly longer than that of Group B (4.1 months; P = 0.026). The 1-year survival rate of Group A was 65.9%, significantly higher than that of Group B (40.9%; P = 0.021), whereas the median overall survival times were 13.5 versus 12.5 months for Groups A and B, respectively (P = 0.483). The adverse effects in the two groups were essentially the same.

Conclusions: Biomarker-tailored chemotherapy based on ERCC1, RRM1, and β-tubulin III expression showed significantly increased response rate, median PFS time, and 1-year survival rate in patients with NSCLC.

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Biomarkers, Tumor / metabolism
  • Bronchoscopy / methods
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cisplatin* / administration & dosage
  • Cisplatin* / adverse effects
  • DNA-Binding Proteins / metabolism*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Disease-Free Survival
  • Drug Screening Assays, Antitumor
  • Endonucleases / metabolism*
  • Feasibility Studies
  • Female
  • Gemcitabine
  • Humans
  • Image-Guided Biopsy / methods
  • Immunohistochemistry
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prospective Studies
  • Ribonucleoside Diphosphate Reductase
  • Tomography, X-Ray Computed / methods
  • Treatment Outcome
  • Tubulin / metabolism*
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • TUBB3 protein, human
  • Tubulin
  • Tumor Suppressor Proteins
  • Deoxycytidine
  • RRM1 protein, human
  • Ribonucleoside Diphosphate Reductase
  • ERCC1 protein, human
  • Endonucleases
  • Cisplatin
  • Gemcitabine