Skip to main content

Advertisement

Springer Nature Link
Log in

Should we still be using bolus 5-FU prior to infusional regimens in gastrointestinal cancers? A practical review

  • Review article
  • Published:
International Cancer Conference Journal Aims and scope Submit manuscript

Abstract

5-fluorouracil (5-FU), a pyrimidine analogue with antimetabolite activity, is one of the most widely used drugs in Oncology and many different regimens have been described regarding its use. Nowadays, the modified de Gramont is the most popular schedule of 5-FU to treat gastrointestinal cancers and may be given either alone or combined with irinotecan, oxaliplatin and monoclonal antibodies. The true clinical value of bolus 5-FU right before infusional regimens remains to be determined since no randomized trials have addressed this issue. This manuscript aims to review the history of 5-FU, its mechanism of action and the data exploring the role of bolus 5-FU.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Daniel BL, Paul DH, Patrick GJ (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3:330–338. https://doi.org/10.1038/nrc1074

    Article  CAS  Google Scholar 

  2. Heidelberger C, Chaudhuri NK, Danneberg P et al (1957) Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 179:663–666. https://doi.org/10.1038/179663a0

    Article  CAS  PubMed  Google Scholar 

  3. Moertel CG, Schutt AJ, Reitemeier RJ et al (1972) A double blind comparison of 5-fluorouracil administered by slow infusion and rapid injection. Cancer Res 32:2717–2719

    CAS  PubMed  Google Scholar 

  4. Curreri AK, Ansfiel FJ, Mclver FA, Waisman HA, Heidelberger C (1958) Clinical studies with 5- fluorouracil. Cancer Res 18:478–484

    CAS  PubMed  Google Scholar 

  5. Ansfield FJ, Schroeder JM, Curreri AR (1962) Five years clinical experience with 5-fluorouracil. JAMA 181:295–299. https://doi.org/10.1001/jama.1962.03050300015003

    Article  CAS  PubMed  Google Scholar 

  6. Flam M, John M, Pajak TF et al (1996) Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14:2527–2539. https://doi.org/10.1200/JCO.1996.14.9.2527

    Article  CAS  PubMed  Google Scholar 

  7. Seifert P, Baker LH, Reed MD et al (1975) Comparison of continuously infused 5-fluorouracil with bolus injection in patients with colorectal adenocarcinoma. Cancer 36:123–128. https://doi.org/10.1002/1097-0142(197507)36:1%3c123::aid-cncr2820360108%3e3.0.co;2-c

    Article  CAS  PubMed  Google Scholar 

  8. Lokich JJ, Ahlgren JD, Gullo JJ et al (1989) A prospective randomized comparison of continuous infusion fluorouracil with a conventional bolus schedule in metastatic colorectal carcinoma. J Clin Oncol 7:425–432. https://doi.org/10.1200/JCO.1989.7.4.425

    Article  CAS  PubMed  Google Scholar 

  9. Weinerman R, Shah A, Fields A et al (1992) Systemic infusion versus bolus chemotherapy with 5-fluorouracil in measurable metastatic colorectal cancer. Am J Clin Oncol 15:518–523. https://doi.org/10.1097/00000421-199212000-00012

    Article  CAS  PubMed  Google Scholar 

  10. Hansen RM, Ryan I, Anderson T et al (1996) Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer. J Natl Cancer Inst 88:668–674. https://doi.org/10.1093/jnci/88.10.668

    Article  CAS  PubMed  Google Scholar 

  11. Piedbois P, Rougier P, Buyse M et al (1998) Meta-analysis Group in Cancer: Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. J Clin Oncol 16:301–308. https://doi.org/10.1200/JCO.1998.16.1.301

    Article  CAS  PubMed  Google Scholar 

  12. de Gramont A, Bosset JF, Milan C, Rougier P, Bouché O, Etienne PL, Morvan F, Louvet C, Guillot T, François E, Bedenne L (1997) Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin and fluorouracil bolus plus continuous infusion for advanced colorectal cancer: a French intergroup study. J Clin Oncol 15(2):808–815. https://doi.org/10.1200/JCO.1997.15.2.808

    Article  PubMed  Google Scholar 

  13. Hryniuk WM, Figueredo A, Goodyear M (1987) Applications of dose intensity to problems in chemotherapy of breast and colorectal cancer. Sem Oncol 14:3–11

    CAS  Google Scholar 

  14. Leichman CG, Leichman L, Spears CP et al (1993) Prolonged continuous infusion of fluorouracil with weekly bolus leucovorin: a phase II study in patients with disseminated colorectal cancer. J Natl Cancer Inst 85:41–44. https://doi.org/10.1093/jnci/85.1.41

    Article  CAS  PubMed  Google Scholar 

  15. Cancer TM-AGI (2004) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis. J Clin Oncol 22:3766–3775. https://doi.org/10.1200/JCO.2004.03.104

    Article  CAS  Google Scholar 

  16. Parker WB, Cheng YC (1990) Metabolism and mechanism of action of 5-fluorouracil. Pharmacol Ther 48:381–395. https://doi.org/10.1016/0163-7258(90)90056-8

    Article  CAS  PubMed  Google Scholar 

  17. McEvoy GK (ed) (2006) AHFS 2006 drug information. American Society of Health-System Pharmacists, Bethesda, pp 1052–1056

    Google Scholar 

  18. Longley DB, Latif T, Boyer J et al (2003) The interaction of thymidylate synthase expression with p53-regulated signaling pathways in tumor cells. Semin Oncol 30:3–9. https://doi.org/10.1016/s0093-7754(03)00119-2

    Article  CAS  PubMed  Google Scholar 

  19. Grem JL (1997) Mechanisms of action and modulation of fluorouracil. Semin Radiat Oncol 7:249–259. https://doi.org/10.1053/SRAO00700249

    Article  CAS  PubMed  Google Scholar 

  20. BC Cancer Drug Manual© Page 2 of 7 Leucovorin Developed: September 1994 Revised: 1 August 2019. http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Fluorouracil_monograph.pdf

  21. He YF, Wei W, Zhang X et al (2008) Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in Chinese cancer patients. J Clin Pharm Ther 33:307–314. https://doi.org/10.1111/j.1365-2710.2008.00898.x

    Article  CAS  PubMed  Google Scholar 

  22. Ardalan B, Waldman S, Sklaver L (1990) The pyrimidine antagonists: 5-fluorouracil and floxuridine. In: Lokich J (ed) Cancer chemotherapy by infusion, 2nd edn. Precept Press, Chicago, pp 85–121

    Google Scholar 

  23. Sobrero AF, Aschele C, Guglielmi AP et al (1993) Synergism and lack of cross-resistance between short-term and continuous exposure to fluorouracil in human colon adenocarcinoma cells. J Natl Cancer Inst 85:1937–1944. https://doi.org/10.1093/jnci/85.23.1937

    Article  CAS  PubMed  Google Scholar 

  24. Yoshida Y, Hasegawa J, Nezu R et al (2011) Clinical significance of bolus 5-fluorouracil for recurrent or metastatic colorectal cancer treated with FOLFOX+ BevacizumabTherapy. Gan To Kagaku Ryoho 38:1293–1296

    PubMed  Google Scholar 

  25. Grothey A, Hart LL, Rowland KM et al (2008) Intermittent oxaliplatin (oxali) administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): Final results of the phase III CONcePT trial. Proc Am Soc Clin Oncol 26:180s. https://doi.org/10.1200/jco.2008.26.15_suppl.4010

    Article  Google Scholar 

  26. Alexa B, Anand S, Katelyn S et al (2020) Impact of empirically eliminating 5-fluorouracil (5-FU) bolus and leucovorin (LV) in patients with metastatic colorectal cancer (mCRC) receiving first-line treatment with mFOLFOX6. Proc Am Soc Clin Oncol 38:15. https://doi.org/10.1200/JCO.2020.38.15_suppl.4022 (Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 4022-4022)

    Article  Google Scholar 

  27. Walid LS, Amber D, Kalu K et al (2021) Survival analysis of colorectal cancer patients treated with first-line modified FOLFOX6 with or without bolus fluorouracil. Proc Am Soc Clin Oncol. https://doi.org/10.1200/JCO.2021.39.3_suppl.35 (Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021) 35-35)

    Article  Google Scholar 

  28. Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825. https://doi.org/10.1056/NEJMoa1011923

    Article  CAS  PubMed  Google Scholar 

  29. Mahaseth H, Brutcher E, Kauh J et al (2013) Modified FOLFIRINOX regimen with improved safety and maintained efficacy in pancreatic adenocarcinoma. Pancreas 42:1311–1315. https://doi.org/10.1097/MPA.0b013e31829e2006

    Article  CAS  PubMed  Google Scholar 

  30. Ozaka M, Ishii H, Sato T et al (2018) A phase II study of modified FOLFIRINOX for chemotherapy-naïve patients with metastatic pancreatic cancer. Cancer Chemother Pharmacol 81:1017–1023. https://doi.org/10.1007/s00280-018-3577-9

    Article  CAS  PubMed  Google Scholar 

  31. Wang Z-Q, Zhang F, Deng T et al (2019) The efficacy and safety of modified FOLFIRINOX as first-line chemotherapy for Chinese patients with metastatic pancreatic cancer. Cancer Commun (Lond) 39(1):26. https://doi.org/10.1186/s40880-019-0367-7

    Article  Google Scholar 

  32. Conroy T, Hammel P, Hebbar M et al (2018) FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med 379:2395–2406. https://doi.org/10.1056/NEJMoa1809775

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No funding sources.

Author information

Authors and Affiliations

  1. Centro Paulista de Oncologia (Grupo Oncoclínicas), Av. Faria Lima, 4300, 6th floor, Sao Paulo, 04538-132, Brazil

    Larissa Costa Amorim & Renata D’Alpino Peixoto

Authors
  1. Larissa Costa Amorim
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Renata D’Alpino Peixoto
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Renata D’Alpino Peixoto.

Ethics declarations

Conflict of interest

No conflict of interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amorim, L.C., Peixoto, R.D. Should we still be using bolus 5-FU prior to infusional regimens in gastrointestinal cancers? A practical review. Int Canc Conf J 11, 2–5 (2022). https://doi.org/10.1007/s13691-021-00526-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13691-021-00526-7

Keywords