@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 UGT1A1 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 = {Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) 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 UGT1A1 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 UGT1A1 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;
p = 0.071], OS (40.0 months vs. 30.0 months; 95% CI, 0.410–1.008; HR, 0.643; p = 0.054), ORR (65.3% vs.
62.7%; p = 0.720), DCR (92.8% vs. 86.7%; p = 0.175), metastatectomy (36.7% vs. 29.3%; p = 0.307), and
SAEs (p = 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 p > 0.05). Our results revealed that patients
with wild-type RAS mCRC, regardless of biologics, with UGT1A1 genotyping can tolerate escalated doses of
irinotecan and potentially achieve a more favorable clinical outcome without significantly increased toxicity.},
DOI = {10.3727/096504022X16451187313084}
}