Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Pharmacokinetics-based Dose Management of 5-Fluorouracil Clinical Research in Advanced Colorectal Cancer Treatment

Author(s): Rong Deng, Lin Shi, Wei Zhu, Mei Wang, Xin Guan, DeLiang Yang and Bo Shen*

Volume 20, Issue 2, 2020

Page: [161 - 167] Pages: 7

DOI: 10.2174/1389557519666191011154923

Price: $65

Abstract

Objective: The study aimed to explore the efficacy of pharmacokinetic-based 5-fluorouracil dose management by plasma concentration test in advanced colorectal cancer treatment.

Methods: 153 samples of advanced colorectal cancer patients were enrolled and randomly assigned to a control group and an experimental group. All patients received double-week chemotherapy with 5- fluorouracil (four weeks were used as one period), and chemotherapy duration ranged from 2 to 6 periods. In the first period, all patients were administered with the classic strategy of body surface area (BSA).

Results: In the subsequent periods, the control group (77 samples) continued with BSA guided chemotherapy, while the experimental group (76 samples) received pharmacokinetic AUC-based chemotherapy. The efficacy and toxic side effects were assessed during chemotherapy, and survival was recorded in a follow-up. In the AUC experimental group, the rate of diarrhea significantly decreased (37.50% vs. 70.00%, P=0.010), and incidence of oral mucositis reduced (54.17% vs. 82.50%, P=0.014). Compared with the control group, the clinical benefit rate of experimental group was much higher (90.79% vs. 79.22%, P=0.046).

Conclusion: There was no significant difference in other 5-fluorouracil related toxic side effect events (nausea, vomiting, hand-foot syndrome) and progression-free survival between the two groups. Pharmacokinetic- based dose management of 5-Fluorouracil reduces the toxicity of chemotherapy and improves long-term efficacy of chemotherapy for advanced colorectal cancer patients.

Keywords: Colorectal cancer, 5-Fluorouracil, pharmacokinetics, cancer patients, DNA, uridylic acid.

« Previous Next »
Graphical Abstract

[1]
Chen, W.; Zheng, R.; Baade, P.D.; Zhang, S.; Zeng, H.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in China, 2015. CA Cancer J. Clin., 2016, 66(2), 115-132.
[http://dx.doi.org/10.3322/caac.21338] [PMID: 26808342]
[2]
Lee, J.J.; Beumer, J.H.; Chu, E. Therapeutic drug monitoring of 5-fluorouracil. Cancer Chemother. Pharmacol., 2016, 78(3), 447-464.
[http://dx.doi.org/10.1007/s00280-016-3054-2] [PMID: 27217046]
[3]
van Kuilenburg, A.B.; Maring, J.G. Evaluation of 5-fluorouracil pharmacokinetic models and therapeutic drug monitoring in cancer patients. Pharmacogenomics, 2013, 14(7), 799-811.
[http://dx.doi.org/10.2217/pgs.13.54] [PMID: 23651027]
[4]
Kaldate, R.R.; Haregewoin, A.; Grier, C.E.; Hamilton, S.A.; McLeod, H.L. Modeling the 5-fluorouracil area under the curve versus dose relationship to develop a pharmacokinetic dosing algorithm for colorectal cancer patients receiving FOLFOX6. Oncologist, 2012, 17(3), 296-302.
[http://dx.doi.org/10.1634/theoncologist.2011-0357] [PMID: 22382460]
[5]
Caudle, K.E.; Thorn, C.F.; Klein, T.E.; Swen, J.J.; McLeod, H.L.; Diasio, R.B.; Schwab, M. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin. Pharmacol. Ther., 2013, 94(6), 640-645.
[http://dx.doi.org/10.1038/clpt.2013.172] [PMID: 23988873]
[6]
Highlights from5-Fluorouracil Drug Management Pharmacokinetics and Pharmacogenomics Workshop; Orlando, Florida; January 2007. Clin. Colorectal Cancer, 2007, 6(6), 407-422.
[http://dx.doi.org/10.1016/S1533-0028(11)70480-7] [PMID: 17539192]
[7]
Kline, C.L.; Schiccitano, A.; Zhu, J.; Beachler, C.; Sheikh, H.; Harvey, H.A.; Mackley, H.B.; McKenna, K.; Staveley-O’Carroll, K.; Poritz, L.; Messaris, E.; Stewart, D.; Sivik, J.; El-Deiry, W.S. Personalized dosing via pharmacokinetic monitoring of 5-fluorouracil might reduce toxicity in early- or late-stage colorectal cancer patients treated with infusional 5-fluorouracil-based chemotherapy regimens. Clin. Colorectal Cancer, 2014, 13(2), 119-126.
[http://dx.doi.org/10.1016/j.clcc.2013.11.001] [PMID: 24461492]
[8]
Wilhelm, M.; Mueller, L.; Miller, M.C.; Link, K.; Holdenrieder, S.; Bertsch, T.; Kunzmann, V.; Stoetzer, O.J.; Suttmann, I.; Braess, J.; Birkmann, J.; Roessler, M.; Moritz, B.; Kraff, S.; Salamone, S.J.; Jaehde, U. Prospective, multicenter study of 5-Fluorouracil therapeutic drug monitoring in metastatic colorectal cancer treated in routine clinical practice. Clin. Colorectal Cancer, 2016, 15(4), 381-388.
[http://dx.doi.org/10.1016/j.clcc.2016.04.001] [PMID: 27256667]
[9]
Wang, Y.; Cao, W.; Yu, Z.; Liu, Z. Downregulation of a mitochondria associated protein SLP-2 inhibits tumor cell motility, proliferation and enhances cell sensitivity to chemotherapeutic reagents. Cancer Biol. Ther., 2009, 8(17), 1651-1658.
[http://dx.doi.org/10.4161/cbt.8.17.9283] [PMID: 19597348]
[10]
Eisenhauer, EA; Therasse, P; Bogaerts, J; Schwartz, LH; Sargent, D; Ford, R; Dancey, J; Arbuck, S; Gwyther, S; Mooney, M; Rubinstein, L; Shankar, L; Dodd, L; Kaplan, R; Lacombe, D; Verweij, J New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Europ. J. Cancer (Oxford, England : 1990), 2009, 45, 228-47.
[11]
Saam, J.; Critchfield, G.C.; Hamilton, S.A.; Roa, B.B.; Wenstrup, R.J.; Kaldate, R.R. Body surface area-based dosing of 5-fluoruracil results in extensive interindividual variability in 5-fluorouracil exposure in colorectal cancer patients on FOLFOX regimens. Clin. Colorectal Cancer, 2011, 10(3), 203-206.
[http://dx.doi.org/10.1016/j.clcc.2011.03.015] [PMID: 21855044]
[12]
Kunzmann, V; Link, K; Miller, MC; Holdenrieder, S; Bertsch, T; Mueller, L; Ko, YD; Stoetzer, OJ; Suttmann, I; Braess, J A prospective, multi-center study of individualized, pharmacokinetically (PK)-guided dosing of 5-fluorouracil (5-FU) in metastatic colorectal cancer (mCRC) patients treated with weekly or biweekly 5- FU/oxaliplatin containing regimens., 2015.
[13]
Braiteh, F.S.; Salamone, S.J.; Li, Y.; Courtney, J.B.; Duda, M.; Diamond, S.; Miller, M.C. Pharmacokinetic (PK)-guided optimization of 5-fluorouracil (5FU) exposure in colorectal cancer (CRC) patients: U.S.-based clinical practices experience. J. Viral Hepat., 2014, 13, 104-115.
[14]
Morawska, K.; Goirand, F.; Marceau, L.; Devaux, M.; Cueff, A.; Bertaut, A.; Vincent, J.; Bengrine-Lefevre, L.; Ghiringhelli, F.; Schmitt, A. 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer. Oncotarget, 2018, 9(14), 11559-11571.
[http://dx.doi.org/10.18632/oncotarget.24338] [PMID: 29545919]
[15]
Cao, W.; Zhang, B.; Liu, Y.; Li, H.; Zhang, S.; Fu, L.; Niu, Y.; Ning, L.; Cao, X.; Liu, Z.; Sun, B. High-level SLP-2 expression and HER-2/neu protein expression are associated with decreased breast cancer patient survival. Am. J. Clin. Pathol., 2007, 128(3), 430-436.
[http://dx.doi.org/10.1309/C6X54HRB580EP2NQ] [PMID: 17709317]
[16]
Cao, W.F.; Zhang, L.Y.; Liu, M.B.; Tang, P.Z.; Liu, Z.H.; Sun, B.C. Prognostic significance of stomatin-like protein 2 overexpression in laryngeal squamous cell carcinoma: Clinical, histologic, and immunohistochemistry analyses with tissue microarray. Hum. Pathol., 2007, 38(5), 747-752.
[http://dx.doi.org/10.1016/j.humpath.2006.11.004] [PMID: 17306333]
[17]
Baker, S.D.; Verweij, J.; Rowinsky, E.K.; Donehower, R.C.; Schellens, J.H.; Grochow, L.B.; Sparreboom, A. Role of body surface area in dosing of investigational anticancer agents in adults, 1991-2001. J. Natl. Cancer Inst., 2002, 94(24), 1883-1888.
[http://dx.doi.org/10.1093/jnci/94.24.1883] [PMID: 12488482]
[18]
Gamelin, E.; Boisdron-Celle, M.; Guérin-Meyer, V.; Delva, R.; Lortholary, A.; Genevieve, F.; Larra, F.; Ifrah, N.; Robert, J. Correlation between uracil and dihydrouracil plasma ratio, fluorouracil (5-FU) pharmacokinetic parameters, and tolerance in patients with advanced colorectal cancer: A potential interest for predicting 5-FU toxicity and determining optimal 5-FU dosage. J. Clin. Oncol., 1999, 17(4), 1105.
[http://dx.doi.org/10.1200/JCO.1999.17.4.1105] [PMID: 10561167]

Rights & Permissions Print Cite
Article Metrics
23
© 2024 Bentham Science Publishers | Privacy Policy