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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()()
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 bevaci...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700286/ https://www.ncbi.nlm.nih.gov/pubmed/26692528 http://dx.doi.org/10.1016/j.tranon.2015.11.002 |
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author | Lu, Chien-Yu Huang, Ching-Wen Wu, I-Chen Tsai, Hsiang-Lin Ma, Cheng-Jen Yeh, Yung-Sung Chang, Se-Fen Huang, Meng-Lin Wang, Jaw-Yuan |
author_facet | Lu, Chien-Yu Huang, Ching-Wen Wu, I-Chen Tsai, Hsiang-Lin Ma, Cheng-Jen Yeh, Yung-Sung Chang, Se-Fen Huang, Meng-Lin Wang, Jaw-Yuan |
author_sort | Lu, Chien-Yu |
collection | PubMed |
description | 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/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. |
format | Online Article Text |
id | pubmed-4700286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47002862016-02-01 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()() Lu, Chien-Yu Huang, Ching-Wen Wu, I-Chen Tsai, Hsiang-Lin Ma, Cheng-Jen Yeh, Yung-Sung Chang, Se-Fen Huang, Meng-Lin Wang, Jaw-Yuan Transl Oncol Original article 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/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. Neoplasia Press 2015-12-12 /pmc/articles/PMC4700286/ /pubmed/26692528 http://dx.doi.org/10.1016/j.tranon.2015.11.002 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Lu, Chien-Yu Huang, Ching-Wen Wu, I-Chen Tsai, Hsiang-Lin Ma, Cheng-Jen Yeh, Yung-Sung Chang, Se-Fen Huang, Meng-Lin Wang, Jaw-Yuan 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()() |
title | 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()() |
title_full | 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()() |
title_fullStr | 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()() |
title_full_unstemmed | 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()() |
title_short | 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()() |
title_sort | 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()() |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700286/ https://www.ncbi.nlm.nih.gov/pubmed/26692528 http://dx.doi.org/10.1016/j.tranon.2015.11.002 |
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