First-line gefitinib combined with simplified FOLFOX-6 in patients with epidermal growth factor receptor-positive advanced colorectal cancer

Abstract

3659 Background: The orally active epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib (IRESSA) shows promising activity in several tumor types. Preclinical studies suggest gefitinib has synergistic activity in combination with oxaliplatin in colorectal cancer (CRC) cells. This Phase II multicenter study evaluated gefitinib combined with FOLFOX-6 as first-line treatment in patients (pts) with EGFR-positive advanced CRC. Methods: Pts received gefitinib 250 mg/day combined with simplified FOLFOX-6 every 2 weeks for ≥8 weeks in order to be evaluable for response. Treatment was continued until progressive disease (PD), unacceptable toxicity, or withdrawal. Pts with clinical benefit after up to a maximum of 10 courses could continue gefitinib monotherapy. Tumor assessment (CT scan) by RECIST was made at baseline and every 4 cycles. All adverse events (AEs) were assessed by NCI-CTC. Serum EGFR was evaluated at baseline and every assessment. Results: 47/49 pts met the entry criteria: 21 male, 26 female; median age 58 years (range 39–76); ECOG performance status 0/1/2: 33/10/4; stage IV at diagnosis: 37 (78.7%); 1/2/>2 disease sites: 23/16/8. At a median follow-up of 4.3 months 39 pts were evaluable for efficacy (8 too early): 29 (74.4%) PR; 9 (23.1%) SD; 1 (2.6%) PD. In 42 pts evaluable for safety (259 cycles), grade 3/4 AEs occurred in 40.5% of pts: neutropenia/leukopenia (16.7%), diarrhea (14.3%), mucositis (7.1%), nausea (4.8%), and fatigue (4.8%). As yet it is too early to assess survival or the role of gefitinib as maintenance therapy. Serum EGFR data (n=27) did not correlate with response. Conclusions: These preliminary data show that first-line gefitinib combined with simplified FOLFOX-6 has promising activity in pts with advanced CRC. Final data will be reported at the meeting. No significant financial relationships to disclose.