Phase II Study of Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), and Celecoxib, a cyclooxygenase-2 (COX-2) Inhibitor, in Patients With Platinum Refractory Non-Small Cell Lung Cancer (NSCLC)

J Thorac Oncol. 2007 Apr;2(4):299-305. doi: 10.1097/01.JTO.0000263712.61697.69.


Background: Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated a response rate of 9%-18% in relapsed non-small cell lung cancer (NSCLC) patients. The probability of response to gefitinib was not influenced by response to previous chemotherapy. Preclinical studies have suggested that celecoxib, a cyclooxygenase-2 inhibitor, has antitumor activity in NSCLC and can enhance the activity of EGFR inhibitors. We conducted a phase II study evaluating the combination of gefitinib and celecoxib in platinum-refractory NSCLC patients, defined as patients whose disease had progressed on platinum-based chemotherapy or within 3 months of completing such therapy.

Methods: Platinum-refractory NSCLC patients with performance status of 0-2 and adequate organ function were included. Patients should not have been on a NSAID for 30 continuous days before study enrollment. Patients were treated with gefitinib 250 mg daily and celecoxib 400 mg twice daily. Disease assessment was performed every 8 weeks.

Results: Twenty-seven patients were enrolled. The response rate was 7% (2/27). The median time to progression was 2.2 months, and the median survival was 4.6 months. One female, nonsmoking patient is progression free more than 3 years after study enrollment. The drug combination was well tolerated, with the most common adverse effects being skin rash and diarrhea.

Conclusion: In unselected platinum-refractory NSCLC patients, the response rate to the combination of celecoxib and gefitinib was similar to that observed with gefitinib alone.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Celecoxib
  • Confidence Intervals
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm*
  • ErbB Receptors / antagonists & inhibitors*
  • Female
  • Follow-Up Studies
  • Gefitinib
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Staging
  • Platinum / therapeutic use*
  • Probability
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Risk Assessment
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Survival Analysis


  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Quinazolines
  • Sulfonamides
  • Platinum
  • ErbB Receptors
  • Celecoxib
  • Gefitinib