Leucovorin

Generic Name
Leucovorin
Brand Names
EnBrace HR, EnLyte, Lederle Leucovorin
Drug Type
Small Molecule
Chemical Formula
C20H23N7O7
CAS Number
58-05-9
Unique Ingredient Identifier
Q573I9DVLP
Background

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.

Indication

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.

Associated Conditions
Advanced Colorectal Cancer, Advanced Esophageal Cancers, Anemia of Pregnancy, Bladder Cancer, Folate and iron deficiency, Folate deficiency, Folic acid antagonist overdose, Iron Deficiency (ID), Macrocytic anemia, Megaloblastic anemia, Pancreatic Metastatic Cancer, Postpartum Anemia, Stage IV Gastric Cancer, Hypochromic anemia, Methotrexate toxicity, Normochromic anemia, Pyrimethamine hematologic toxicity
Associated Therapies
-

A Phase 1/2 Study of INCB001158 in Combination With Chemotherapy in Subjects With Solid Tumors

First Posted Date
2017-10-19
Last Posted Date
2023-12-07
Lead Sponsor
Incyte Corporation
Target Recruit Count
149
Registration Number
NCT03314935
Locations
🇺🇸

Northwest Georgia Oncology Centers, Marietta, Georgia, United States

🇺🇸

USA Mitchell Cancer Center, Mobile, Alabama, United States

🇺🇸

University of Alabama, Birmingham, Alabama, United States

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A Study of Multiple Immunotherapy-Based Treatment Combinations in Patients With Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Cancer (G/GEJ) or Esophageal Cancer (Morpheus-Gastric and Esophageal Cancer)

First Posted Date
2017-09-13
Last Posted Date
2024-10-26
Lead Sponsor
Hoffmann-La Roche
Target Recruit Count
410
Registration Number
NCT03281369
Locations
🇺🇸

Uni of Southern California; Norris Comprehensive Cancer Ctr, Los Angeles, California, United States

🇺🇸

Tennessee Oncology - Nashville, Nashville, Tennessee, United States

🇦🇺

Peter MacCallum Cancer Centre; Medical Oncology, Melbourne, Victoria, Australia

and more 33 locations

A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers

First Posted Date
2017-09-12
Last Posted Date
2022-10-05
Lead Sponsor
Massachusetts General Hospital
Target Recruit Count
25
Registration Number
NCT03279237
Locations
🇺🇸

Massachusetts General Hospital, Boston, Massachusetts, United States

Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)

First Posted Date
2017-07-18
Last Posted Date
2024-10-18
Lead Sponsor
Merck Sharp & Dohme LLC
Target Recruit Count
1007
Registration Number
NCT03221426
Locations
🇺🇸

Fox Chase Cancer Center ( Site 0006), Philadelphia, Pennsylvania, United States

🇨🇦

Cross Cancer Institute ( Site 0033), Edmonton, Alberta, Canada

🇨🇦

Jewish General Hospital ( Site 0034), Montreal, Quebec, Canada

and more 168 locations

PEN-866 in Patients With Advanced Solid Malignancies

First Posted Date
2017-07-18
Last Posted Date
2022-02-17
Lead Sponsor
Tarveda Therapeutics
Target Recruit Count
340
Registration Number
NCT03221400
Locations
🇺🇸

Florida Cancer Specialists - North, Saint Petersburg, Florida, United States

🇺🇸

Florida Cancer Specialists - South, Fort Myers, Florida, United States

🇺🇸

Florida Cancer Specialists - East, West Palm Beach, Florida, United States

and more 13 locations

CMAB009 Combined With FOLFIRI First-line Treatment in Patients With RAS/BRAF Wild-type, Metastatic Colorectal Cancer

First Posted Date
2017-07-02
Last Posted Date
2024-11-07
Lead Sponsor
Taizhou Mabtech Pharmaceutical Co.,Ltd
Target Recruit Count
520
Registration Number
NCT03206151
Locations
🇨🇳

Cancer hospital Chinese academy of medical sciences, Beijing, Beijing, China

🇨🇳

Tianjing medical university cancer institute and hospital, Tianjin, Tianjin, China

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