@Article{096504022X16451187313084,
AUTHOR = {Hsiang-Lin Tsai, Yen-Cheng Chen, Tzu-Chieh Yin, Wei-Chih Su, Po-Jung Chen,Tsung-Kun Chang, Ching-Chun Li, Ching-Wen Huang, Jaw-Yuan Wang},
TITLE = {Comparison of <i>UGT1A1</i> Polymorphism as Guidance of Irinotecan Dose  Escalation in RAS Wild-Type Metastatic Colorectal Cancer Patients Treated  With Cetuximab or Bevacizumab Plus FOLFIRI as the First-Line Therapy},
JOURNAL = {Oncology Research},
VOLUME = {29},
YEAR = {2021},
NUMBER = {1},
PAGES = {47--61},
URL = {http://www.techscience.com/or/v29n1/48452},
ISSN = {1555-3906},
ABSTRACT = {<i>Uridine diphosphate glucuronosyltransferase 1A1</i> (<i>UGT1A1</i>) polymorphism plays a crucial role in the increased 
susceptibility and toxicity of patients to irinotecan. This retrospective, observational study compared the clinical outcomes and adverse events (AEs) in RAS wild-type metastatic colorectal cancer (mCRC) patients treated 
with cetuximab or bevacizumab plus FOLFIRI with <i>UGT1A1</i> genotyping and irinotecan dose escalation as the 
first-line therapy. In total, 173 patients with mCRC with RAS wild-type were enrolled. Among them, 98 patients 
were treated with cetuximab, whereas 75 patients were treated with bevacizumab. All patients received irinotecan dose escalation based on <i>UGT1A1</i> genotyping. We compared the progression-free survival (PFS), overall 
survival (OS), objective response rates (ORRs), disease control rates (DCRs), metastatectomy, and severe 
adverse events (SAEs) between the two groups. The clinical effects of primary tumor sidedness and target 
therapy crossover were further analyzed. Over a median follow-up of 23.0 months [interquartile range (IQR), 
15.0–32.5 months], no significant differences were observed between the cetuximab and bevacizumab groups 
in PFS [18.0 months vs. 14.0 months; 95% confidence interval (CI), 0.517–1.027; hazard ratio (HR), 0.729; 
<i>p</i> = 0.071], OS (40.0 months vs. 30.0 months; 95% CI, 0.410–1.008; HR, 0.643; <i>p</i> = 0.054), ORR (65.3% vs. 
62.7%; <i>p</i> = 0.720), DCR (92.8% vs. 86.7%; <i>p</i> = 0.175), metastatectomy (36.7% vs. 29.3%; <i>p</i> = 0.307), and 
SAEs (<i>p</i> = 0.685). Regardless of primary tumor sidedness and target therapy crossover, no significant differences were noted in efficacy and safety between the two groups (all <i>p</i> > 0.05). Our results revealed that patients 
with wild-type RAS mCRC, regardless of biologics, with <i>UGT1A1</i> genotyping can tolerate escalated doses of 
irinotecan and potentially achieve a more favorable clinical outcome without significantly increased toxicity.},
DOI = {10.3727/096504022X16451187313084}
}