Meeting Abstract | 2004 ASCO Annual Meeting


Background: The epidermal growth factor receptor and cyclooxygenase 2 (COX2) may be targeted with inhibitors such as gefitinib (‘Iressa’, ZD1839) and rofecoxib, respectively. Methods: This Phase I/II study evaluated the safety, efficacy and pharmacokinetic interactions of gefitinib 250 mg po daily with rofecoxib in platinum-pretreated NSCLC. Rofecoxib was escalated through 3 cohorts of 6 patients from 12.5 (Level 1) to 25 (Level 2) and 50 mg po od (Level 3), the dose at which >90% of COX-2 activity is inhibited, with the final cohort expanded to 27 patients. Results: Analysis is complete on 33 recruited patients. The treatment appears generally well tolerated, the main toxicities including skin rash (grade 1/2, 44%; grade 3/4, 3%) and diarrhoea (grade 1/2, 22%). One patient at Level 1 was withdrawn due to grade 1 renal toxicity. Another had a cerebrovascular accident occurring on Day 31. Time to tumour progression was 54 days (range 46–64 days). Of 31 patients evaluable for response, 1 complete response and 2 partial responses were seen, with stable disease recorded in a further 9, giving a disease control rate of 39%. Preliminary results for a panel of potential surrogate serum/plasma markers of response indicate that IFNγ, TNFα, IL2, IL4, IL6, IL10 and big-endothelin-1 levels are similar in responders and non-responders at baseline and over time. An ongoing global serum proteomic analysis will assess if responders can be distinguished from non-responders. Study recruitment is complete and final results will be presented at the meeting. Conclusion: The combination of gefitinib with rofecoxib is generally well tolerated and may have a role to play in the management of NSCLC. 'Iressa' is a trademark of the AstraZeneca group of companies

Author Disclosure

Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration
AstraZeneca Pharmaceuticals

American Society of Clinical Oncology


No companion articles


DOI: 10.1200/jco.2004.22.90140.7101 Journal of Clinical Oncology 22, no. 14_suppl (July 15, 2004) 7101-7101.

Published online July 15, 2004.

ASCO Career Center