Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST)
| Autor: | Yung-Chuan Sung, Jui-Ho Wang, Yi-Wen Lin, Hsiu-Chin Tang, Hsuan-Yuan Huang, Hsiang-Lin Tsai, Chang-Chieh Wu, Jaw-Yuan Wang, Hwei-Ming Wang, Ching-Wen Huang, Tzu-Liang Chen, Tao-Wei Ke, Chang-Sung Tsai, Joe-Bin Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Oncology Adult Male Cancer Research medicine.medical_specialty Bevacizumab Genotype Colorectal cancer Leucovorin Irinotecan Proto-Oncogene Proteins p21(ras) 03 medical and health sciences 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols Outcome Assessment Health Care Medicine Humans Glucuronosyltransferase Neoplasm Metastasis Adverse effect Aged Aged 80 and over Polymorphism Genetic business.industry Middle Aged medicine.disease Clinical trial Regimen 030104 developmental biology 030220 oncology & carcinogenesis FOLFIRI Camptothecin Female Fluorouracil Metastasectomy business Colorectal Neoplasms medicine.drug |
| Zdroj: | European journal of cancer (Oxford, England : 1990). 138 |
| ISSN: | 1879-0852 0225-6800 |
| Popis: | Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy.The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. The primary end-point was progression-free survival (PFS), and secondary end-points were overall response rate (ORR), disease control rate (DCR), overall survival (OS), AEs and metastasectomy rate.Over a median follow-up of 26.0 months (IQR, 17.0-35.0 months), study group (n = 107) was superior to the control group (n = 106) in PFS, OS, ORR, DCR, and metastasectomy rate (all P 0.05). Furthermore, there were no significant differences in AEs ≥ grade III between the two groups, even with the 1.36-fold increase in the relative dose intensity of irinotecan in the study group. Dose escalation of irinotecan, an independent factor of ORR (P 0.001) and DCR (P = 0.006), improved PFS in mCRC patients with wild-type and mutant KRAS (P = 0.007 and P = 0.019, respectively).The current study revealed that mCRC patients, regardless of KRAS gene status, with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favourable clinical outcome without significantly increased toxicities.NCT02256800. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect