Journal
TRANSLATIONAL ONCOLOGY
Volume 8, Issue 6, Pages 474-479Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2015.11.002
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Funding
- Excellence for Cancer Research Center [MOST104-2325-B-037-001]
- Ministry of Health and Welfare, Taiwan, Republic of China [MOHW 104-TDU-B-212-124-003]
- Kaohsiung Medical University Hospital [KMUH100-0M01, KMUH100-0M16, KMUH103-3R16, KMUHS10304, KMUHS10305]
- Center for Biomarkers and Biotech Drugs, Kaohsiung Medical University [KMU-TP103C00, KMU-TP103C03, KMU-TP103C07, KMU-TP103H11, KMU-TP104A11]
- Grant of Biosignature in Colorectal Cancers, Academia Sinica, Taiwan
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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 180mg/m(2) dose of irinotecan, and UGT1A1 *28/*28 genotype started with a dose of 120 mg/m(2). The dose of irinotecan was escalated at increasing intervals of 20 to 30 mg/m(2) 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<.001, respectively). Grade 3/4 AEs were significantly more common in mCRC patients with the UGT1A1 *28/*28 genotype (P<.001). Progression-free survival was significantly higher in UGT1A1 *1/*1 and *1/*28 patients (P=.002). mCRC patients who underwent metastasectomy achieved better overall survival than those who did not undergo metastasectomy (P=.015). CONCLUSIONS: Our study showed that mCRC patients with UGT1A1 *1/*1 and *1/*28 genotypes could receive escalated doses of irinotecan to obtain a more favorable clinical outcome without significant AEs.
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