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Preclinical evaluation of novel, all-in-one formulations of 5-fluorouracil and folinic acid with reduced toxicity profiles

Journal Article


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Abstract


  • 5-Fluorouracil (5-FU) in combination with its synergistic biomodulator folinic acid maintains a pivotal position in cancer chemotherapy. However, clinical limitations such as phlebitis and catheter blockages persist with the administration of these drugs in combination, and are associated with reduced efficacy and/or quality of life for patients. We have reported earlier on the novel, all-in-one, pH neutral, parenteral 5-FU and folinic acid formulations (termed Fluorodex) incorporating beta-cyclodextrins. Fluorodex maintains potency while overcoming the accepted incompatibility of 5-FU and folinic acid. We carried out toxicological, pharmacokinetic and biodistribution, and efficacy evaluations of Fluorodex compared with 5-FU:folinic acid using several administration routes and schedules in two rodent models. These were compared with the dose-matched sequential administration of 5-FU:folinic acid. Fluorodex showed bioequivalence to 5-FU:folinic acid as assessed by the tissue distribution and pharmacokinetic studies of 5-FU, but was generally better tolerated as determined by weight loss, hematological, and other clinical parameters. Compared with 5-FU:folinic acid, Fluorodex was also associated with reduced phlebitis using a rabbit ear vein model. Furthermore, using human carcinoma tumor models in mice, Fluorodex resulted in equivalent or improved efficacy profiles compared with 5-FU:folinic acid. In conclusion, these novel, all-in-one formulations represent a superior injectable form of 5-FU that allows codelivery of folinic acid. This should translate into improved patient tolerability with potential for enhanced efficacy.

Publication Date


  • 2011

Citation


  • Stutchbury, T., Vine, K. L., Locke, J., Chrisp, J. S., Bremner, J. B., Clingan, P. R. & Ranson, M. (2011). Preclinical evaluation of novel, all-in-one formulations of 5-fluorouracil and folinic acid with reduced toxicity profiles. AntiCancer Drugs: international journal on anti-cancer agents, 22 (1), 24-34.

Scopus Eid


  • 2-s2.0-78650517767

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1209&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/177

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 24

End Page


  • 34

Volume


  • 22

Issue


  • 1

Abstract


  • 5-Fluorouracil (5-FU) in combination with its synergistic biomodulator folinic acid maintains a pivotal position in cancer chemotherapy. However, clinical limitations such as phlebitis and catheter blockages persist with the administration of these drugs in combination, and are associated with reduced efficacy and/or quality of life for patients. We have reported earlier on the novel, all-in-one, pH neutral, parenteral 5-FU and folinic acid formulations (termed Fluorodex) incorporating beta-cyclodextrins. Fluorodex maintains potency while overcoming the accepted incompatibility of 5-FU and folinic acid. We carried out toxicological, pharmacokinetic and biodistribution, and efficacy evaluations of Fluorodex compared with 5-FU:folinic acid using several administration routes and schedules in two rodent models. These were compared with the dose-matched sequential administration of 5-FU:folinic acid. Fluorodex showed bioequivalence to 5-FU:folinic acid as assessed by the tissue distribution and pharmacokinetic studies of 5-FU, but was generally better tolerated as determined by weight loss, hematological, and other clinical parameters. Compared with 5-FU:folinic acid, Fluorodex was also associated with reduced phlebitis using a rabbit ear vein model. Furthermore, using human carcinoma tumor models in mice, Fluorodex resulted in equivalent or improved efficacy profiles compared with 5-FU:folinic acid. In conclusion, these novel, all-in-one formulations represent a superior injectable form of 5-FU that allows codelivery of folinic acid. This should translate into improved patient tolerability with potential for enhanced efficacy.

Publication Date


  • 2011

Citation


  • Stutchbury, T., Vine, K. L., Locke, J., Chrisp, J. S., Bremner, J. B., Clingan, P. R. & Ranson, M. (2011). Preclinical evaluation of novel, all-in-one formulations of 5-fluorouracil and folinic acid with reduced toxicity profiles. AntiCancer Drugs: international journal on anti-cancer agents, 22 (1), 24-34.

Scopus Eid


  • 2-s2.0-78650517767

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1209&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/177

Has Global Citation Frequency


Number Of Pages


  • 10

Start Page


  • 24

End Page


  • 34

Volume


  • 22

Issue


  • 1