First clinical experience of orally active epidermal growth factor receptor inhibitor combined with simplified FOLFOX6 as first-line treatment for metastatic colorectal cancer

BACKGROUND. Gefitinib, an orally active inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, combined with chemotherapy, has shown efficacy as second-line treatment for advanced colorectal cancer (CRC). Gefitinib combined with FOLFOX6 (oxaliplatin plus folinic acid and 5-fluorouracil) was tested as a first-line therapy. METHODS. Patients with metastatic EGFR-positive CRC received gefitinib at a dose of 250 mg/day combined with simplified FOLFOX6. Gefitinib was continued as maintenance treatment in nonprogressing patients. Responses were assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria and adverse events were assessed with the National Cancer Institute Common Toxicity Criteria (NCI-CTC) scale. RESULTS. A total of 56 patients were recruited. There were 26 men and 30 women, with a median age of 57.5 years. The Eastern Cooperative Oncology Group (ECOG) performance status was as follows: 0 in 39 patients, 1 in 12 patients, and 2 in 5 patients. Thirty-nine patients (69.6%) had stage IV disease at diagnosis, 92.9% had liver involvement, and 46.4% had >= 2 metastatic sites. All patients were evaluated for safety, and 53 were evaluated for response: 40 patients (71.4%; 95% confidence interval [95% CI], 57.8%-82.6%) had complete or partial responses, and 11 patients (19.6%) had stable disease. Median time to progression was 7 months (range, 2.1-33.0 months; 95% Cl, 6.2-9.0 months). Radical surgery or thermoablation of metastatic sites was performed in 14 patients (25%). NCI-CTC grade 3-4 events occurred in 36 patients (64.3%): diarrhea in 9 patients (16.1%), and hematologic toxicity in 13 patients (23.2%). Four patients (7.1%) were withdrawn for drug-related adverse events. CONCLUSIONS. The regimen has shown promising efficacy with manageable toxicity as a first-line treatment for patients with advanced CRC.