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Leucovorin calcium/Levoleucovorin
Leucovorin calcium and levoleucovorin are reduced folate cofactors that enhance the efficacy of antimetabolite chemotherapy agents by providing essential one-carbon units for nucleotide synthesis.
Leucovorin calcium and levoleucovorin are reduced folate cofactors that enhance the efficacy of antimetabolite chemotherapy agents by providing essential one-carbon units for nucleotide synthesis. Used for Metastatic colorectal cancer (in combination with fluorouracil), High-dose methotrexate toxicity rescue, Fluorouracil-based chemotherapy potentiation.
At a glance
| Generic name | Leucovorin calcium/Levoleucovorin |
|---|---|
| Also known as | Folinic acid |
| Sponsor | Janssen Research & Development, LLC |
| Drug class | Reduced folate cofactor; chemotherapy adjuvant |
| Target | Thymidylate synthase (indirect); folate metabolism pathway |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | Phase 3 |
Mechanism of action
Leucovorin (folinic acid) and its active L-isomer levoleucovorin bypass the dihydrofolate reductase step and directly provide 5,10-methylenetetrahydrofolate, a critical cofactor for thymidylate synthase and other folate-dependent enzymes. This potentiates the cytotoxic effects of fluorouracil and methotrexate by stabilizing their target enzyme complexes and enhancing DNA synthesis inhibition. Levoleucovorin is the pharmacologically active form, requiring lower doses than the racemic leucovorin calcium.
Approved indications
- Metastatic colorectal cancer (in combination with fluorouracil)
- High-dose methotrexate toxicity rescue
- Fluorouracil-based chemotherapy potentiation
Common side effects
- Allergic sensitization
- Nausea and vomiting
- Stomatitis
- Diarrhea
- Myelosuppression (when combined with chemotherapy)
Key clinical trials
- Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (PHASE2)
- A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer (PHASE3)
- Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06) (PHASE1, PHASE2)
- Combination Chemotherapy Before and After Surgery in Treating Patients With Localized Pancreatic Cancer (PHASE2)
- Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (PHASE3)
- A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy (PHASE3)
- Neoadjuvant mFOLFOX6 Chemotherapy Combined With Anti-PD-1 Therapy in MSS/pMMR Locally Advanced Rectal Cancer (FIRM02 Study) (PHASE2)
- Phase 2 Futibatinib in Combination With PD-1 Antibody Based Standard of Care in Solid Tumors (PHASE2)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
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