Abstract
7101 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 One patient at Level 1 was withdrawn due to grade 1 renal toxicity.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
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