Phase II trial of dose-dense chemotherapy followed by dose-intense erlotinib for patients with newly diagnosed metastatic non-small cell lung cancer

Int J Oncol. 2013 Dec;43(6):2057-63. doi: 10.3892/ijo.2013.2122. Epub 2013 Oct 3.


This phase II study investigated dose-intense erlotinib maintenance after dose-dense chemotherapy for patients with metastatic non-small cell lung cancer and examined two cell cycle biomarkers. Patients with newly diagnosed metastatic non-small cell lung cancer received docetaxel 75 mg/m² and cisplatin 75 mg/m² on day 1 and pegfilgrastim on day 2 every 14 days for four cycles. Patients then received erlotinib with initial doses based on smoking status. Doses were increased in 75 mg increments every two weeks depending on toxicities until each patient's maximal tolerable dose (MTD) was achieved. Cyclin D1 and D3 biomarkers were measured by immunohistochemistry. The objectives of the study were to evaluate time to progression (TTP) and overall survival (OS) for the entire population and biomarker subgroups. Forty-five patients were enrolled. Intra-patient erlotinib MTD ranged from 0 to 525 mg. Median MTD achieved in smokers was higher than in non-smokers (300 vs. 150 mg; P=0.019). TTP for the entire cohort was not significantly improved compared to historical controls. Patients with high cyclin D1 expressing tumors demonstrated improved TTP on erlotinib (8.2 vs. 4.7 months; hazard ratio, 4.1; 95% CI, 1.6-0.6; P=0.003) and improved OS (20.5 vs. 8.0 months; hazard ratio 2.8; 95% CI, 1.2-6.3; P=0.016). Intratumoral cyclin D3 expression did not impact clinical outcomes. Current smokers but not former smokers exhibit a higher erlotinib MTD. High cyclin D1 expression was associated with favorable TTP and OS.

Trial registration: NCT00723138.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cisplatin / therapeutic use
  • Cyclin D1 / metabolism
  • Cyclin D3 / metabolism
  • Disease-Free Survival
  • Docetaxel
  • Drug Administration Schedule
  • ErbB Receptors / antagonists & inhibitors*
  • Erlotinib Hydrochloride
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Polyethylene Glycols
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / therapeutic use*
  • Recombinant Proteins / therapeutic use
  • Survival
  • Taxoids / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CCND3 protein, human
  • Cyclin D3
  • Protein Kinase Inhibitors
  • Quinazolines
  • Recombinant Proteins
  • Taxoids
  • Cyclin D1
  • Granulocyte Colony-Stimulating Factor
  • Docetaxel
  • pegfilgrastim
  • Polyethylene Glycols
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Filgrastim
  • Cisplatin

Associated data