Clinical implication of UGT1A1 promoter polymorphism for irinotecan dose escalation in metastatic colorectal cancer patients treated with bevacizumab combined with FOLFIRI in the first-line setting

Abstract

PURPOSE: This study aimed to identify the efficacy and toxicity of the FOLFIRI regimen (fluorouracil, leucovorin, and irinotecan) with irinotecan dose escalation plus bevacizumab as first-line chemotherapy for metastatic colorectal cancer (mCRC) via UGT1A1 genotyping. METHODS: We administered bevacizumab plus FOLFIRI with irinotecan dose escalation to treat 70 mCRC patients. The UGT1A1 *1/*1 and *1/*28 genotypes started with a 180- mg/m2 dose of irinotecan, and UGT1A1 *28/*28 genotype started with a dose of 120 mg/m2. The dose of irinotecan was escalated at increasing intervals of 20 to 30 mg/m2 until grade 3/4 adverse events (AEs) occurred. The clinical response rate, toxicity, and survival were analyzed. RESULTS: The clinical response and disease control rates of mCRC patients treated with FOLFIRI plus bevacizumab were significantly better in patients with UGT1A1 *1/*1 and *1/*28 genotypes than in patients with UGT1A1 *28/*28 (P = .006 and P