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
-

FOLFOX/Bevacizumab/Hydroxychloroquine (HCQ) in Colorectal Cancer

First Posted Date
2010-09-22
Last Posted Date
2019-04-18
Lead Sponsor
Abramson Cancer Center at Penn Medicine
Target Recruit Count
50
Registration Number
NCT01206530
Locations
🇺🇸

Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania, United States

A Study in Second Line Metastatic Colorectal Cancer

First Posted Date
2010-08-18
Last Posted Date
2019-09-25
Lead Sponsor
Eli Lilly and Company
Target Recruit Count
1072
Registration Number
NCT01183780
Locations
🇨🇳

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician., Taipei, Taiwan

Lenalidomide in Combination With Bevacizumab, Sorafenib, Temsirolimus, or 5-Fluorouracil, Leucovorin, Oxaliplatin (FOLFOX)

First Posted Date
2010-08-17
Last Posted Date
2016-06-03
Lead Sponsor
M.D. Anderson Cancer Center
Target Recruit Count
180
Registration Number
NCT01183663
Locations
🇺🇸

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

Biomarker-Guided Fluorouracil in Treating Patients With Colorectal Cancer Receiving Combination Chemotherapy

First Posted Date
2010-07-16
Last Posted Date
2015-10-09
Lead Sponsor
UNC Lineberger Comprehensive Cancer Center
Target Recruit Count
76
Registration Number
NCT01164215
Locations
🇺🇸

Cancer Care of Western North Carolina, Asheville, North Carolina, United States

🇺🇸

Moses Cone Regional Cancer Center at Wesley Long Community Hospital, Greensboro, North Carolina, United States

🇺🇸

Marion L. Shepard Cancer Center, Washington, North Carolina, United States

and more 2 locations

Oxaliplatin, Leucovorin Calcium, and Fluorouracil With or Without Celecoxib in Treating Patients With Stage III Colon Cancer Previously Treated With Surgery

First Posted Date
2010-06-24
Last Posted Date
2022-03-22
Lead Sponsor
Alliance for Clinical Trials in Oncology
Target Recruit Count
2527
Registration Number
NCT01150045
Locations
🇺🇸

Mount Carmel Hospital East, Columbus, Ohio, United States

🇺🇸

Riverside Methodist Hospital, Columbus, Ohio, United States

🇺🇸

Helen F Graham Cancer Center, Newark, Delaware, United States

and more 836 locations

Randomized Study With Oxaliplatin in 2nd Line Pancreatic Cancer

First Posted Date
2010-05-12
Last Posted Date
2014-10-27
Lead Sponsor
Sanofi
Target Recruit Count
108
Registration Number
NCT01121848
Locations
🇨🇦

Investigational Site Number 124011, Greenfield Park, Canada

🇨🇦

Investigational Site Number 124010, Hamilton, Canada

🇨🇦

Investigational Site Number 124008, Sudbury, Canada

and more 12 locations

Pyrimethamine as a Treatment for Late-Onset GM2-gangliosidosis (Tay-Sachs and Sandhoff Disease)

First Posted Date
2010-04-13
Last Posted Date
2012-02-23
Lead Sponsor
The Hospital for Sick Children
Target Recruit Count
20
Registration Number
NCT01102686
Locations
🇨🇦

The Hospital for Sick Children, Toronto, Ontario, Canada

Five Fractions of Radiotherapy Followed by Full Dose FOLFOX Chemotherapy as Preoperative Treatment for Rectal Cancer

First Posted Date
2010-02-01
Last Posted Date
2017-03-08
Lead Sponsor
Washington University School of Medicine
Target Recruit Count
80
Registration Number
NCT01060007
Locations
🇺🇸

Washington University School of Medicine, St. Louis, Missouri, United States

Combination of Brivanib With 5-Fluorouracil/Leucovorin (5FU/LV) and 5-Fluorouracil/Leucovorin/Irinotecan (FOLFIRI)

First Posted Date
2010-01-12
Last Posted Date
2014-09-16
Lead Sponsor
Bristol-Myers Squibb
Target Recruit Count
49
Registration Number
NCT01046864
Locations
🇺🇸

Scott & White Memorial Hospital And Clinic, Temple, Texas, United States

🇺🇸

Texas Oncology, Dallas, Texas, United States

🇺🇸

Usc/Norris Comprehensive Cancer Center, Los Angeles, California, United States

and more 1 locations
© Copyright 2024. All Rights Reserved by MedPath