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Intrathecal injection of pemetrexed
Pemetrexed inhibits multiple folate-dependent enzymes involved in nucleotide synthesis, disrupting DNA and RNA production in cancer cells when delivered directly into the cerebrospinal fluid.
Pemetrexed inhibits multiple folate-dependent enzymes involved in nucleotide synthesis, disrupting DNA and RNA production in cancer cells when delivered directly into the cerebrospinal fluid. Used for Leptomeningeal metastases (carcinomatous meningitis), CNS lymphoma.
At a glance
| Generic name | Intrathecal injection of pemetrexed |
|---|---|
| Sponsor | Union Hospital, Tongji Medical College, Huazhong University of Science and Technology |
| Drug class | Antifolate antimetabolite |
| Target | Thymidylate synthase, dihydrofolate reductase, glycinamide ribonucleotide formyltransferase |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
Mechanism of action
Pemetrexed is a multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase, blocking purine and pyrimidine synthesis. When administered intrathecally, it achieves high local concentrations in the central nervous system to treat leptomeningeal malignancies while minimizing systemic exposure.
Approved indications
- Leptomeningeal metastases (carcinomatous meningitis)
- CNS lymphoma
Common side effects
- Neurotoxicity
- Myelosuppression
- Chemical arachnoiditis
- Headache
- Fever
Key clinical trials
- Intrathecal Injection Pemetrexed And Bevacizumab in Patients With Leptomeningeal Metastases in NSCLC (PHASE1)
- Intrathecal Chemotherapy Through Ommaya Reservoir Upon Her-2 Negative Breast Cancer With Leptomeningeal Metastasis (PHASE4)
- Firmonertinib Combined With Intrathecal Injection for the Treatment of EGFR Mutant NSCLC With Leptomeningeal Metastases (PHASE4)
- Intrathecal Combination of Programmed Death-1 (PD-1)/Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA-4) Bispecific Antibody and Pemetrexed for Leptomeningeal Metastasis (PHASE1, PHASE2)
- Intrathecal PD-1/VEGF Bispecific Antibody Plus Pemetrexed for Leptomeningeal Metastasis (PHASE1, PHASE2)
- Intrathecal Dual Checkpoint Inhibitor (PD-1 and CTLA-4) in Combination With Pemetrexed for Leptomeningeal Metastasis (PHASE1, PHASE2)
- Intrathecal Pemetrexed for Leptomeningeal Metastasis (PHASE1, PHASE2)
- Cerebrospinal Fluid Cytology-guided Intrathecal Chemo-holiday Therapy for EGFR-positive NSCLC Leptomeningeal Metastases (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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