title: 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).
abstract: 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.
  
  
  CONCLUSIONS
  In unselected platinum-refractory NSCLC patients, the response rate to the combination of celecoxib and gefitinib was similar to that observed with gefitinib alone.
authors.affiliation: Karmanos Cancer Institute/Wayne State University, Detroit, Michigan, USA. gadgeels@karmanos.org
authors.forename: Shirish M
authors.initials: SM
authors.lastname: Gadgeel
authors.forename: John C
authors.initials: JC
authors.lastname: Ruckdeschel
authors.forename: Elisabeth I
authors.initials: EI
authors.lastname: Heath
authors.forename: Lance K
authors.initials: LK
authors.lastname: Heilbrun
authors.forename: Raghu
authors.initials: R
authors.lastname: Venkatramanamoorthy
authors.forename: Antoinette
authors.initials: A
authors.lastname: Wozniak
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000068579:Celecoxib; D016001:Confidence Intervals; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000627:therapeutic use*; D011336:Probability; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018570:Risk Assessment; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D011799:Quinazolines; D013449:Sulfonamides; D010984:Platinum; D066246:ErbB Receptors; D000068579:Celecoxib; D000077156:Gefitinib