Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer

O'Byrne, Kenneth J., Danson, Sarah, Dunlop, David, Botwood, Nick, Taguchi, Fumiko, Carbone, David, & Ranson, Malcolm (2007) Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer. Journal of Clinical Oncology, 25(22), pp. 3266-3273.

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Purpose: In non-small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45).

Patients and Methods: Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33).

Results: Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea.

Conclusion: Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs. © 2007 by American Society of Clinical Oncology.

Impact and interest:

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33 citations in Web of Science®
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ID Code: 65257
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: carboplatin, cisplatin, docetaxel, gefitinib, gemcitabine, ifosfamide, mitomycin, navelbine, platinum, rofecoxib, vinblastine, abdominal pain, adult, aged, area under the curve, article, cancer epidemiology, cancer patient, cancer survival, clinical article, clinical trial, combination chemotherapy, dermatitis, diarrhea, disease control, drug dose comparison, drug dose escalation, drug efficacy, drug safety, drug screening, drug withdrawal, dry skin, dyspepsia, dyspnea, female, human, kidney disease, loose feces, lung non small cell cancer, male, matrix assisted laser desorption ionization time of flight mass spectrometry, metastasis, monotherapy, nausea, phase 1 clinical trial, phase 2 clinical trial, priority journal, pruritus, rash, recurrent disease, squamous cell carcinoma, stomatitis, treatment response, tumor growth, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Disease Progression, Drug Administration Schedule, Humans, Lactones, Lung Neoplasms, Middle Aged, Neoplasm Recurrence, Local, Proteomics, Quinazolines, Sulfones, Survival Rate, Treatment Outcome
DOI: 10.1200/JCO.2006.09.2791
ISSN: 0732-183X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2007 by American Society of Clinical Oncology
Deposited On: 10 Dec 2013 02:52
Last Modified: 11 Mar 2014 01:37

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