PMID- 35177165
OWN - NLM
STAT- MEDLINE
DCOM- 20220505
LR  - 20230524
IS  - 1555-3906 (Electronic)
IS  - 0965-0407 (Print)
IS  - 0965-0407 (Linking)
VI  - 29
IP  - 1
DP  - 2022 May 4
TI  - 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.
PG  - 47-61
LID - 10.3727/096504022X16451187313084 [doi]
AB  - 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), 15.032.5 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), 
      0.5171.027; hazard ratio (HR), 0.729; p=0.071], OS (40.0 months vs. 30.0 months; 
      95% CI, 0.4101.008; 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.
FAU - Tsai, Hsiang-Lin
AU  - Tsai HL
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Chen, Yen-Cheng
AU  - Chen YC
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Yin, Tzu-Chieh
AU  - Yin TC
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Su, Wei-Chih
AU  - Su WC
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Chen, Po-Jung
AU  - Chen PJ
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Chang, Tsung-Kun
AU  - Chang TK
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Li, Ching-Chun
AU  - Li CC
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Huang, Ching-Wen
AU  - Huang CW
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
FAU - Wang, Jaw-Yuan
AU  - Wang JY
AD  - Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical 
      University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan.
LA  - eng
PT  - Journal Article
PT  - Observational Study
DEP - 20220217
PL  - United States
TA  - Oncol Res
JT  - Oncology research
JID - 9208097
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 7673326042 (Irinotecan)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - PQX0D8J21J (Cetuximab)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Bevacizumab/therapeutic use
MH  - Camptothecin
MH  - Cetuximab/therapeutic use
MH  - *Colonic Neoplasms/drug therapy
MH  - *Colorectal Neoplasms/drug therapy/genetics
MH  - Fluorouracil
MH  - Glucuronosyltransferase/genetics
MH  - Humans
MH  - Irinotecan/adverse effects
MH  - Leucovorin/therapeutic use
MH  - Retrospective Studies
PMC - PMC9110692
COIS- The authors declare no conflicts of interest.
EDAT- 2022/02/19 06:00
MHDA- 2022/05/06 06:00
PMCR- 2022/05/04
CRDT- 2022/02/18 05:33
PHST- 2022/02/19 06:00 [pubmed]
PHST- 2022/05/06 06:00 [medline]
PHST- 2022/02/18 05:33 [entrez]
PHST- 2022/05/04 00:00 [pmc-release]
AID - OR1480 [pii]
AID - 10.3727/096504022X16451187313084 [doi]
PST - ppublish
SO  - Oncol Res. 2022 May 4;29(1):47-61. doi: 10.3727/096504022X16451187313084. Epub 
      2022 Feb 17.