Korean J Gastroenterol.  2024 Sep;84(3):123-127. 10.4166/kjg.2024.087.

Current Status of Chemotherapy in Colorectal Cancer: Updated Treatment Strategies

• Kim JH
• Park SJ

• KMID: 2559845
• DOI: http://doi.org/10.4166/kjg.2024.087

Abstract

Colorectal cancer remains a significant health burden in South Korea, being the third most diagnosed cancer in the country. Despite advances in treatment, patients with metastatic colorectal cancer still face limited survival rates, with resection often deemed impossible for the majority. This review discusses the current state of chemotherapy in colorectal cancer treatment, focusing on both adjuvant chemotherapy post-surgery and palliative chemotherapy for metastatic cases. The article highlights recent updates in treatment guidelines, including the use of immunotherapy and the role of circulating tumor DNA (ctDNA) in personalized medicine. The integration of these novel approaches aims to enhance treatment efficacy, improve patient survival, and reduce recurrence rates, paving the way for more tailored and effective therapeutic strategies in colorectal cancer management.

Keyword

Colorectal neoplasm; Chemotherapy

Reference

1. Jung KW, Won YJ, Hong S, Kong HJ, Im JS, Seo HG. 2021; Prediction of cancer incidence and mortality in Korea, 2021. Cancer Res Treat. 53:316–322. DOI: 10.4143/crt.2021.290. PMID: 33735558. PMCID: PMC8053854.

2. Moertel CG, Fleming TR, Macdonald JS, et al. 1990; Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 322:352–358. DOI: 10.1056/NEJM199002083220602. PMID: 2300087.

3. Loupakis F, Cremolini C, Masi G, et al. 2014; Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 371:1609–1618. DOI: 10.1056/NEJMoa1403108. PMID: 25337750.

4. Saif MW. 2009; Secondary hepatic resection as a therapeutic goal in advanced colorectal cancer. World J Gastroenterol. 15:3855–3864. DOI: 10.3748/wjg.15.3855. PMID: 19701965. PMCID: PMC2731247.

5. 2024. NCCN Clinical Practive Guidelines in Oncology: Colon Cancer version 5. [Internet]. National Comprehensive Cancer Network;Available from: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428. cited 2024 Sep 1.

6. Sun Z, Adam MA, Kim J, et al. 2016; Determining the optimal timing for initiation of adjuvant chemotherapy after resection for stage II and III colon cancer. Dis Colon Rectum. 59:87–93. DOI: 10.1097/DCR.0000000000000518. PMID: 26734965.

7. Bos AC, van Erning FN, van Gestel YR, et al. 2015; Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. Eur J Cancer. 51:2553–2561. DOI: 10.1016/j.ejca.2015.08.016. PMID: 26360411.

8. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. 2011; Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 305:2335–2342. DOI: 10.1001/jama.2011.749. PMID: 21642686.

9. André T, de Gramont A, Vernerey D, et al. 2015; Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: Updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 33:4176–4187. DOI: 10.1200/JCO.2015.63.4238. PMID: 26527776.

10. André T, Boni C, Mounedji-Boudiaf L, et al. 2004; Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 350:2343–2351. DOI: 10.1056/NEJMoa032709. PMID: 15175436.

11. Wilson RH, Lehky T, Thomas RR, Quinn MG, Floeter MK, Grem JL. 2002; Acute oxaliplatin-induced peripheral nerve hyperexcitability. J Clin Oncol. 20:1767–1774. DOI: 10.1200/JCO.2002.07.056. PMID: 11919233.

12. Grothey A, Sobrero AF, Shields AF, et al. 2018; Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 378:1177–1188. DOI: 10.1056/NEJMoa1713709. PMID: 29590544. PMCID: PMC6426127.

13. Best L, Simmonds P, Baughan C, et al. 2000; Palliative chemotherapy for advanced or metastatic colorectal cancer. Colorectal Meta-analysis Collaboration. Cochrane Database Syst Rev. 2000:CD001545. DOI: 10.1002/14651858.CD001545. PMID: 10796809. PMCID: PMC7025779.

14. Hou W, Yi C, Zhu H. 2022; Predictive biomarkers of colon cancer immunotherapy: Present and future. Front Immunol. 13:1032314. DOI: 10.3389/fimmu.2022.1032314. PMID: 36483562. PMCID: PMC9722772.

15. Gibney GT, Weiner LM, Atkins MB. 2016; Predictive biomarkers for checkpoint inhibitor-based immunotherapy. Lancet Oncol. 17:e542–e551. DOI: 10.1016/S1470-2045(16)30406-5. PMID: 27924752. PMCID: PMC5702534.

16. Le DT, Uram JN, Wang H, et al. 2015; PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 372:2509–2520. DOI: 10.1056/NEJMoa1500596. PMID: 26028255. PMCID: PMC4481136.

17. Lenz HJ, Van Cutsem E, Luisa Limon M, et al. 2022; First-line nivolumab plus low-dose ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: The Phase II CheckMate 142 Study. J Clin Oncol. 40:161–170. DOI: 10.1200/JCO.21.01015. PMID: 34637336.

18. Le DT, Kim TW, Van Cutsem E, et al. 2020; Phase II open-label study of pembrolizumab in treatment-refractory, microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: KEYNOTE-164. J Clin Oncol. 38:11–19. DOI: 10.1200/JCO.19.02107. PMID: 31725351. PMCID: PMC7031958.

19. André T, Shiu KK, Kim TW, et al. 2020; Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med. 383:2207–2218. DOI: 10.1056/NEJMoa2017699. PMID: 33264544.

20. André T, Lonardi S, Wong KYM, et al. 2022; Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142. Ann Oncol. 33:1052–1060. DOI: 10.1016/j.annonc.2022.06.008. PMID: 35764271.

21. Ganesh K, Stadler ZK, Cercek A, et al. 2019; Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol. 16:361–375. DOI: 10.1038/s41575-019-0126-x. PMID: 30886395. PMCID: PMC7295073.

22. Wang F, Zhao Q, Wang YN, et al. 2019; Evaluation of POLE and POLD1 mutations as biomarkers for immunotherapy outcomes across multiple cancer types. JAMA Oncol. 5:1504–1506. DOI: 10.1001/jamaoncol.2019.2963. PMID: 31415061. PMCID: PMC6696731.

23. Garmezy B, Gheeya J, Lin HY, et al. 2022; Clinical and molecular characterization of POLE mutations as predictive biomarkers of response to immune checkpoint inhibitors in advanced cancers. JCO Precis Oncol. 6:e2100267. DOI: 10.1200/PO.21.00267. PMID: 35108036. PMCID: PMC8820927.

24. Domingo E, Freeman-Mills L, Rayner E, et al. 2016; Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study. Lancet Gastroenterol Hepatol. 1:207–216. DOI: 10.1016/S2468-1253(16)30014-0. PMID: 28404093.

25. Tie J, Cohen JD, Lahouel K, et al. 2022; Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 386:2261–2272. DOI: 10.1056/NEJMoa2200075. PMID: 35657320. PMCID: PMC9701133.