Current insight on irinotecan dose adjustment in advanced colorectal cancers based on pharmacogenetic studies: an updated review
Main Article Content
Abstract
Despite advancements in colorectal cancer screening and treatment, the occurrence, severity, and mortality rates have consistently risen among younger patients. Precision medicine aims to personalize cytotoxic drug dosages, such as irinotecan, by considering the pharmacogenetic specificity of glucuronidation backgrounds. Our search, focused on recent developments (2020-2024) in categorizing Uridine 5'-diphosphate-glucuronosyltransferase (UGT)1A1 variants related to irinotecan's safety, effectiveness, and cost-benefit in metastatic colorectal cancer patients identified 32 relevant clinical studies and recent reviews from 296 abstracts in PubMed and PubMed Central databases. This updated review emphasizes racial disparities in the incidence and essential variants influencing irinotecan's activated metabolite (SN-38). While UGT1A1*28 homozygosity is the primary cause of toxicity in North America, Europe, and a Middle Asian country, UGT1A1*6 is the prominent variant responsible in East Asian countries. Despite various methods employed for dose adjustment based on pharmacogenomic findings, individualization of the dose has been associated with reduced toxicity, improved response, and enhanced patient survival. The recommended irinotecan dose in the FOLFIRI regimen can be variable between 120mg/m2 to 350 mg/m2 based on the UGT1A1 genotype variant. Moreover, this approach appears to be cost-effective, as suggested by European and Chinese studies.
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How to Cite
SADIGHI, Sanambar; SHAKER, Pouyan; SHAFIEE, Mohammad Ali.
Current insight on irinotecan dose adjustment in advanced colorectal cancers based on pharmacogenetic studies: an updated review.
Medical Research Archives, [S.l.], v. 12, n. 5, may 2024.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/5266>. Date accessed: 04 dec. 2024.
doi: https://doi.org/10.18103/mra.v12i5.5266.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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4. Chen X, Liu L, Guo Z, Liang W, He J, Huang L, et al. UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in Asians with Lung Cancer: a meta-analysis. Cancer Chemother Pharmacol. 2017;79(6):1109–1117.
5. Li Y, Zheng H, Zhang X, Xi Y, Cheng M, Zhao Y, Wang L and Hua B (2022). UGT1A1 Allele Test Not Only Minimizes the Toxicity But Also Maximizes the Therapeutic Effect of Irinotecan in the Treatment of Colorectal Cancer: A Narrative Review. Front. Oncol. 12:854478.doi: 10.3389/fonc.2022.854478.
6. Li Q, Sun T, Zhang H, Liu W, Xiao Y, Sun H, Yin W, Yao Y, Gu Y, Liu Y, Yi F, Wang Q, Yu J, Cao B, Liang L. Characteristics and Clinical Implication of UGT1A1 Heterozygous Mutation in Tumor. Zhongguo Fei Ai Za Zhi. 2022 Mar 20;25(3):137-146. doi: 10.3779/j.issn.1009-3419.2022.101.07. PMID: 35340156; PMCID: PMC8976199.
7. Roden DM, McLeod HL, Relling MV, Williams MS, Mensah GA, Peterson JF, et al.
Pharmacogenomics. Lancet. 2019; 394:521–32.
8. Nelson RS, Seligson ND, Bottiglieri S, Carballido E, Cueto AD, Imanirad I, Levine R, Parker AS, Swain SM, Tillman EM, Hicks JK. UGT1A1 Guided Cancer Therapy: Review of the Evidence and Considerations for Clinical Implementation. Cancers (Basel). 2021 Mar 29;13(7):1566. doi: 10.3390/cancers13071566.
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https://www.pharmgkb.org/labelAnnotation/PA166182952 file. Downloads/Irinotecan_06_21_19_EMA.pdf
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https://www.fda.gov/regulatory -information/search-fda-guidance-documents/clinical-pharmacogenomics-premarket-evaluation-early-phase-clinical-studies-and-recommendations. Accessed February 19, 2024.
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14. Ma CJ, Chang TK, Tsai HL, Su WC, Huang CW, Yeh YS, Chang YT, Wang JY. Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previously treated metastatic colorectal cancer patients: study protocol for a randomized controlled trial. Trials. 2019 Dec 19;20(1):751. doi: 10.1186/s13063-019-3917-z. PMID: 31856912; PMCID: PMC6923824.
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19. NCCN Clinical Practice Guidelines Version 1.2024 Colon Cancer.
https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf
20. Benson AB, Venook AP, Al-Hawary MM, et al Rectal cancer, version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 20:1139-1167, 2022
21. Takano M, Sugiyama T. UGT1A1 polymorphisms in cancer: impact on irinotecan treatment. Pharmgenomics Pers Med. 2017 Feb 28;10:61-68. doi: 10.2147/PGPM.S108656. PMID: 28280378; PMCID: PMC5338934.
22. Nielson CM, Bylsma LC, Fryzek JP, Saad HA, Crawford J. Relative dose intensity of chemotherapy and survival in patients with advanced stage solid tumor cancer: a systematic review and meta-analysis. Oncologist. 2021; 26(9):e1609–e1618. doi: 10.1002/onco.13822.
23. Hulshof EC, de With M, de Man FM, Creemers GJ, et al. UGT1A1 genotype-guided dosing of irinotecan: a prospective safety and cost analysis in poor metabolizer patients. Eur J Cancer. 2022; 162:148–157. doi: 10.1016/j.ejca.2021.12.009.
24. Emami AH, Sadighi S, Shirkoohi A, Mohagheghi MA. Prediction of Response to Irinotecan and Drug Toxicity Based on Pharmacogenomics Test: A Prospective Case Study in Advanced Colorectal Cancer. Asian Pac J Cancer Prev,( 2017)18 (10), 2803-2807. DOI:10.22034/APJCP.2017.18.10.2803.
25. Tsai HL, Huang CW, Lin YW, et al. Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST). Eur. J. Cancer. 2020;138, 19–29.
26. Páez D, Tobeña M, Fernández-Plana J, et al. Pharmacogenetic clinical randomised Phase II trial to evaluate the efficacy and safety of FOLFIRI with high-dose irinotecan (HD-FOLFIRI) in metastatic colorectal cancer patients according to their UGT1A 1 genotype. Br J Cancer. 2019;120(2):190–195. doi: 10.1038/s41416-018-0348
27. Ginzac A, Thivat E, Petorin C, Richard D, Herviou P, Molnar I, Devaud H, Creveaux I, Ferrer F, Authier N, Jary M, Pezet D, Durando X. A phase-II study based on dose adjustment according to UGT1A1 polymorphism: is irinotecan underdosed in first-line FOLFIRI regimen for mCRC? Cancer Chemother Pharmacol. 2024 Mar;93(3):225-236. doi: 10.1007/s00280-023-04603-x. Epub 2023 Nov 7. PMID: 37932443; PMCID: PMC10901933.
28. Tsai HL, Huang CW, Chen Y, et al. Real-World Outcomes of First-Line FOLFIRI Plus Bevacizumab with Irinotecan Dose Escalation versus FOLFOXIRI Plus Bevacizumab in BRAFV600E-Mutant Metastatic Colorectal Cancer: The Preliminary Data from a Single-Center Observational Study. Medicina 2023, 59, 2108.
https://doi.org/10.3390/medicina59122108.
29. Barone C, Nuzzo G, Cassano A, et al. Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases. Br J Cancer 2007; 97:1035-9. doi: 10.1038/sj.bjc.6603988.
30. Iwasa S, Muro K, Morita S, et al. Impact of UGT1A1 Genotype on the Efficacy and Safety of Irinotecan-Based Chemotherapy in Metastatic Colorectal Cancer. Cancer Sci (2021) 112(11): 4669–78. doi: 10.1111/cas.15092.
31. Wei X, Cai J, Sun H, Li N, Xu C, Zhang G, et al. Cost-effectiveness analysis of UGT1A1*6/*28 genotyping for preventing FOLFIRI-induced severe neutropenia in Chinese colorectal cancer patients. Pharmacogenomics. 2019;20(4):241–9.
32. Sukri A, Salleh MZ, Masimirembwa C, Teh LK. A systematic review on the cost-effectiveness of pharmacogenomics in developing countries: implementation challenges. Pharmacogenomics J. 2022 May;22(3):147-159. doi: 10.1038/s41397-022-00272-w.
33. European Organisation for Research and Treatment (EORTC)—Quality of Life Group. EORTC QLQ-C30. 2021. https://qol.eortc.org/questionnaires/. Accessed 9 Dec 2021.
34. FACIT group. Functional Assessment of Cancer Therapy—General. 2021.
https://www.facit.org/measures/FACT-G. Accessed 9 Dec 2021.