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High-dose intravenous methotrexate
High-dose intravenous methotrexate inhibits dihydrofolate reductase, blocking DNA synthesis and cell division in rapidly proliferating cells.
High-dose intravenous methotrexate inhibits dihydrofolate reductase, blocking DNA synthesis and cell division in rapidly proliferating cells. Used for Hematologic malignancies (lymphomas, leukemias), Osteosarcoma, Breast cancer.
At a glance
| Generic name | High-dose intravenous methotrexate |
|---|---|
| Sponsor | Chonnam National University Hospital |
| Drug class | Antimetabolite; folate antagonist |
| Target | Dihydrofolate reductase (DHFR) |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | Phase 3 |
Mechanism of action
Methotrexate is a folate antagonist that inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate, which is essential for one-carbon transfer reactions and nucleotide synthesis. At high doses administered intravenously, it achieves high intracellular concentrations that are particularly toxic to rapidly dividing cancer cells. High-dose regimens are often followed by leucovorin rescue to protect normal tissues from excessive toxicity.
Approved indications
- Hematologic malignancies (lymphomas, leukemias)
- Osteosarcoma
- Breast cancer
- Head and neck cancers
Common side effects
- Myelosuppression (neutropenia, thrombocytopenia)
- Mucositis
- Nausea and vomiting
- Hepatotoxicity
- Nephrotoxicity
- Neurotoxicity
- Infection
Key clinical trials
- Study Testing Two Conditioning Regimen With a Single Prophylaxis of GVHD by Cyclophosphamide and Methotrexate Post-transplant in Patients Eligible for Matched-donor Allograft Transplantation (PHASE2)
- Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma (PHASE2)
- Evaluation of Acute and Chronic Nephrotoxicity in Acute Lymphatic Leukemia Patients Using Ultrasound Localization Microscopy (NA)
- Mature B-Cell Lymphoma And Leukemia Study III (PHASE2, PHASE3)
- Selinexor in Combination With MTX+Ritu to Treat R/R CNSL (PHASE1, PHASE2)
- HEM-iSMART-C: Ruxolitinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies (PHASE1, PHASE2)
- HEM-iSMART E: Capivasertib + Venetoclax + Dexamethasone in Pediatric Patients With Relapsed or Refractory Hematological Malignancies (PHASE1, PHASE2)
- HEM-iSMART-B: Dasatinib + Venetoclax + Dexamethasone + Cyclophosphamide and Cytarabine in Pediatric Patients With Relapsed or Refractory Hematological Malignancies (PHASE1, 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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