Folinic Acid (also known as 5-formyl tetrahydrofolic acid or leucovorin) is the 5-formyl derivative of tetrahydrofolic acid, a necessary co-factor in the body. Commercially available leucovorin is composed of a 1:1 racemic mixture of the dextrorotary and levorotary isomers, while levoleucovorin contains only the pharmacologically active levo-isomer. In vitro, the levo-isomer has been shown to be rapidly converted to the biologically available methyl-tetrahydrofolate form while the dextro form is slowly excreted by the kidneys. Despite this difference in activity, the two commercially available forms have been shown to be pharmacokinetically identical and may be used interchangeably with limited differences in efficacy or side effects (Kovoor et al, 2009).
As folate analogs, leucovorin and levoleucovorin are both used to counteract the toxic effects of folic acid antagonists, such as methotrexate, which act by inhibiting the enzyme dihydrofolate reductase (DHFR). They are indicated for use as rescue therapy following use of high-dose methotrexate in the treatment of osteosarcoma or for diminishing the toxicity associated with inadvertent overdosage of folic acid antagonists. Injectable forms are also indicated for use in the treatment of megaloblastic anemias due to folic acid deficiency when oral therapy is not feasible and for use in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
Folic acid is an essential B vitamin required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. However, in order to function in this role, it must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted when high-dose methotrexate is used for cancer therapy. As methotrexate functions as a DHFR inhibitor to prevent DNA synthesis in rapidly dividing cells, it also prevents the formation of DHF and THF. This results in a deficiency of coenzymes and a resultant buildup of toxic substances that are responsible for numerous adverse side effects associated with methotrexate therapy. As levoleucovorin and leucovorin are analogs of tetrahydrofolate (THF), they are able to bypass DHFR reduction and act as a cellular replacement for the co-factor THF, thereby preventing these toxic side effects.
For the treatment of osteosarcoma (after high dose methotrexate therapy). Used to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists, and to treat megaloblastic anemias due to folic acid deficiency. Also used in combination with 5-fluorouracil to prolong survival in the palliative treatment of patients with advanced colorectal cancer.
Emory University Hospital Midtown, Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute, Atlanta, Georgia, United States
Emory Saint Joseph's Hospital, Atlanta, Georgia, United States
Sun Yat-sen University Cancer Center, Guanzhou, Guangdong, China
University of Michigan Rogel Cancer Center, Ann Arbor, Michigan, United States
Cancer and Hematology Centers of Western Michigan, Grand Rapids, Michigan, United States
University of Utah, Salt Lake City, Utah, United States
University of Iowa Hospital and Clinics, Iowa City, Iowa, United States
City of Hope, Duarte, California, United States
Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Dong-A University Hospital, Busan, Korea, Republic of
University of California, San Francisco, San Francisco, California, United States
Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, Netherlands
Zuyderland Medisch Centrum, Geleen, Netherlands
Tergooi ziekenhuizen, Hilversum, Netherlands
840-01 - HOAG Memorial Hospital, Newport Beach, California, United States
124-11 - CISSS de Chaudière-Appalaches, Lévis, Quebec, Canada
250-05 - Clinique Sainte Anne, Strasbourg, France
ICO Girona Dr. Josep Trueta, Gerona, Barcelona, Spain
Hospital de Granollers, Granollers, Barcelona, Spain
Hospital Mutua de Terrassa, Terrassa, Barcelona, Spain
Roswell Park Cancer Institute, Buffalo, New York, United States
Stony Brook Cancer Center, Stony Brook, New York, United States
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