High vs. low-dose leucovorin in regimens with fluorouracil in colorectal cancer therapy

Česká verze

Authors: Jan Juřica; Pavlína Šuverová; Roman Goněc; Stanislav Synek; Miroslav Turjap
Published in the journal: Čes. slov. Farm., 2023; 72, 107-112
Category: Původní práce
doi: https://doi.org/10.5817/CSF2023-3-107

Summary

The problem of unavailability of drugs and shortages have been a common problem in recent years. Shortages may threaten some treatment regimens for oncological patients. This article presents a systematic review of studies evaluating the efficacy and safety of chemotherapy regimens combining fluorouracil and standard or low-dose leucovorin in treating colorectal cancer. A total of 13 prospective and retrospective studies were included in the review. Meta-analyses and review papers were excluded. It is apparent from the systematic review that a lower dose of leucovorin does not fundamentally affect the efficacy of regimens combining 5-fluorouracil with leucovorin in treating patients with colorectal cancer. Similarly, even in the case of safety, reducing the dose of leucovorin did not influence the frequency and severity of observed adverse effects. Surprisingly, in three studies, some of the adverse effects occurred more often with the higher dose of leucovorin. Furthermore, the article presents the results of a questionnaire survey of the management of leucovorin shortages at the departments of preparation of cytostatics (N = 46) within the Czech Republic. In total, 35 workplaces provided feedback. In 17 cases, the departments for the preparation of cytostatics in the Czech Republic had to accept restrictions on administering the full dose of leucovorin. These restrictions consisted of reducing the dose of the injectable form of leucovorin, changing the chemotherapy regimen, administering the oral form of calcium folinate, forcing a therapeutic break, or a combination of these approaches.

Keywords:

colorectal cancer – leucovorin – levo-leucovorin – fluorouracil

Zdroje

1. Kiss I. Modrá kniha České onkologické společnosti. Brno: Masarykův onkologický ústav 2021; 303.

2. UpToDate W, MA. Leucovorin. Drug information. UpTo-Date, UpToDate, Waltham, MA., 2022 www.uptodate.com

3. Kiss I. Modrá kniha České onkologické společnosti. Brno: Masarykův onkologický ústav 2022; 33.

4. NCCN. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer 2022; 1–198.

5. Argilés G., Tabernero J., Labianca R., Hochhauser D., Salazar R., Iveson T., Laurent-Puig P., Quirke P., Yoshino T., Taieb J. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2020; 31, 1291–1305.

6. Hsu C., Chen C., Lin Y., Tam K. Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis. Colorectal Dis. 2020; 22, 6–17.

7. Ychou M. Fabbro-Peray, P. Perney, P., Marçais O., Gouze C., Ribard D., Bons-Rosset F., Heran B., Veyrac M., Blanc F. A prospective randomized study comparing high- and low-dose leucovorin combined with samedose 5-fluorouracil in advanced colorectal cancer. Am. J. Clin. Oncol. 1998; 21, 233–236.

8. QUASAR Collaborative Group. Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. Lancet 2000; 355, 1588–1596.

9. Jäger E., Heike M., Bernhard H., Klein O., Bernhard G., Lautz D., Michaelis J., Meyer zum Büschenfelde K.H., Knuth, A. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J. Clin. Oncol. 1996; 14, 2274–2279.

10. Labianca R., Cascinu S., Frontini L., Barni S., Fiorentini G., Comella G., Zaniboni A., Gottardi O., Arnoldi E., Oliani C. High-versus low-dose levo-leucovorin as a modulator of 5-fluorouracil in advanced colorectal cancer: A ‘GISCAD’phase III study. Ann. Oncol. 1997; 8, 169–174.

11. Shank B., Seung A., Kinsman K., Newman M., Donehower R., Burton B. Effects of the leucovorin shortage: Pilot study investigating cost, efficacy, and toxicity comparison of low fixed-dose versus body surface area-adjusted leucovorin dosing in patients with resectable colon or metastatic colorectal cancer. J. Oncol. Pharm. Pract. 2017; 23, 163–172.

12. Buroker T. R., O’Connell M. J., Wieand H. S., Krook J. E., Gerstner J. B., Mailliard J. A., Schaefer P. L., Levitt R., Kardinal C. G., Gesme D. H. Randomized comparison of two schedules of fluorouracil and leucovorin in the treatment of advanced colorectal cancer. J. Clin. Oncol. 1994; 12, 14–20.

13. O’Connell M. J. A phase III trial of 5-fluorouracil and leucovorin in the treatment of advanced colorectal cancer. A Mayo Clinic/North Central Cancer Treatment Group study. Cancer 1989; 63, 1026–1030.

14. Poon M. A., O’Connell M. J., Moertel C. G., Wieand H. S., Cullinan S. A., Everson L. K., Krook J. E., Mailliard J. A., Laurie J. A., Tschetter L. K. Biochemical modulation of fluorouracil with leucovorin: confirmatory evidence of improved therapeutic efficacy in advanced colorectal cancer. J. Clin. Oncol. 1991; 9: 1967–1972.

15. Petrelli N., Douglass H. O., Herrera L., Russell, D. Stablein D. M., Bruckner H. W., Mayer R. J., Schinella R., Green M. D., Muggia F. M. The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group. J Clin. Oncol. 1989; 7, 1419–1426.

16. Reynolds J., Chamberland-Tremblay A., Herrington J.D., Munoz Maldonado Y., Wong L. High- versus lowdose leucovorin in the modified FOLFOX6 regimen for first-line treatment of metastatic colorectal cancer. J. Oncol. Pharm. Pract. 2017; 23, 173–178.

17. Maroun J. A., Cripps C., Goel R., Dahrouge S., Boisvert D. Retrospective comparative analysis of 5FU + lowdose folinic acid vs. 5FU + high-dose folinic acid in the treatment of metastatic colorectal cancer. The Ottawa experience. Am. J. Clin. Oncol. 1997; 20, 387–392.

18. Budai B., Nagy T., Láng I., Hitre E. The use of high dose d,l-leucovorin in first-line bevacizumab+mFOLFIRI treatment of patients with metastatic colorectal cancer may enhance the antiangiogenic effect of bevacizumab. Angiogenesis 2013; 16, 113–121.

19. Elkalla H. M. H. R., Zahi M. S., Eldamshety O. Low-dose versus Standard-Dose Leucovorin in the Treatment of Colon Cancer: Mansoura University Clinical Experience in Facing the Problem of Leucovorin Shortage. Res. Oncol. 2019; 15, 15–19.