Gastrointestinal hemorrhage in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib and celecoxib

Abstract

7172 Background: Erlotinib (E) was associated with superior survival in a phase III trial of previously treated advanced NSCLC patients (pts). Celecoxib (C) has been shown to potentiate the apoptotic and growth inhibitory effects of E in pre-clinical models. Methods: This was a phase II trial of E plus C in advanced NSCLC pts that failed one prior chemotherapy regimen. Primary endpoint: efficacy; secondary endpoint: toxicity. Pts received C (400mg b.i.d.) and E (150mg daily) until disease progression. Planned accrual: 40 pts. Results: 26 pts with stage IIIB/IV NSCLC were enrolled. Patient (pt) characteristics: male 65%; median age 66; ECOG performance status 0/1- 96%. Eighteen pts had tissue available for FISH and EGFR mutation analysis: 50% had chromosome 7 polysomy (> 4 copies per cell); none had EGFR gains (>2 EGFR/chromosome 7). Two pts had an EGFR gene mutation (1 exon 19, 1 exon 21). Response results: partial response- 2 pts (1 with exon 19 mutation), stable disease- 8 pts, and progressive disease- 16 pts (1 with exon 21 mutation). Median progression free survival (PFS) and overall survival (OS): 1.9 and 10.2 months, respectively. Grade 3/4 upper gastrointestinal bleeding (GIB) occurred in 4 pts prompting study closure. One pt was on therapeutic dalteparin and two pts receiving warfarin developed marked INR prolongation (INR >10). The fourth pt had a history of peptic ulcer disease. Platelet counts at time of GIB: 142 - 559. Three pts had endoscopy and gastric or duodenal ulcers were found in all three cases. No pts were taking anti-acid medication at the time of GIB. No other pts were on therapeutic anticoagulation. Three pts without upper GIB were taking low-dose aspirin. Other toxicities: 85% grade 1/2 rash; 65% grade 1/2 diarrhea, 30% grade 1/2 nausea, 30% grade 1/2 fatigue (one grade 3 fatigue); one grade 3 pneumonitis, one grade 3 esophageal stricture. Conclusions: These observations suggest that C plus E may be associated with increased incidence of gastrointestinal ulceration and GIB and that the regimen should not be given to pts with a previous history of peptic ulcer disease or to pts requiring therapeutic anticoagulation. Based on response rate, PFS, and OS in this group of pts, it appears that results with E and C are similar to those reported for E alone. [Table: see text]