Abstract
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.
Original language | English |
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Pages (from-to) | 3266-3273 |
Number of pages | 7 |
Journal | Journal of Clinical Oncology |
Volume | 25 |
Issue number | 22 |
DOIs | |
Publication status | Published - 1 Aug 2007 |
Keywords
- Adult
- Aged
- Aged, 80 and over
- therapeutic use: Antineoplastic Combined Chemotherapy Protocols
- drug therapy: Carcinoma, Non-Small-Cell Lung
- administration & dosage: Cisplatin
- Disease Progression
- Drug Administration Schedule
- Female
- Humans
- administration & dosage: Lactones
- drug therapy: Lung Neoplasms
- Male
- Middle Aged
- Neoplasm Recurrence, Local
- Proteomics
- administration & dosage: Quinazolines
- administration & dosage: Sulfones
- Survival Rate
- Treatment Outcome