Pralatrexate
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Pralatrexate: Pleural adenomatoid tumor
One-Sentence Summary
Pralatrexate is an antifolate originally used to treat peripheral T-cell lymphoma and related mature T-cell and NK-cell lymphomas. The TxGNN model predicts it may be effective for pleural mesothelioma (the top prediction, a benign pleural adenomatoid tumour, has no supporting evidence, so this report focuses on the pleural mesothelioma prediction, which has the most literature), with 0 registered clinical trials and 2 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Pleural adenomatoid tumor |
| TxGNN Prediction Score | 0.9991 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, pralatrexate is an antifolate that inhibits dihydrofolate reductase (DHFR). It enters cells through the reduced folate carrier (RFC-1) and is efficiently polyglutamylated, which helps it stay inside tumour cells.
This is mechanistically close to pemetrexed, the standard antifolate backbone for pleural mesothelioma. Its efficacy in T-cell lymphoma is established, and antifolate activity in mesothelioma is a recognised class effect. A 2007 phase II study of pralatrexate in unresectable malignant pleural mesothelioma and a review of antifolate chemotherapy support the class rationale. Preclinical work cited in the study abstract also reports significant antitumour activity in mesothelioma cell lines and xenografts.
Predictions for other mesothelioma subtypes (epithelioid, biphasic, sarcomatoid, peritoneal, pericardial) are extrapolated from the same class rationale, with no subtype-specific pralatrexate data. The two highest-scoring predictions are weak. The relapsing-remitting multiple sclerosis prediction has no supporting data, and pralatrexate has no known CNS penetration or neuroinflammation evidence.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 17409804 | 2007 | Phase II single-arm trial | J Thorac Oncol | Pralatrexate in unresectable malignant pleural mesothelioma. Background notes a favourable toxicity profile (mainly stomatitis) and antitumour activity in mesothelioma cell lines and xenografts. Efficacy outcomes are not given in the available data. |
| 21301589 | 2010 | Review | Cancer Manag Res | Review of antifolates targeting folate synthesis, supporting the class rationale for DHFR inhibitors in cancer. |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02481820 | FOLOTYN | Not specified | Not specified in the available data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (antifolate, DHFR inhibitor) |
| Myelosuppression Risk | Moderate to high. Thrombocytopenia, neutropenia and anaemia are listed as contraindication-related conditions in the knowledge graph. |
| Emetogenicity Classification | Low |
| Monitoring Items | CBC with differential, renal function, liver function, and mucositis assessment (stomatitis is the main dose-limiting toxicity) |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please also refer to the package insert warnings and precautions.
Safety Considerations
- Conditions flagged in the knowledge graph (not label text): thrombocytopenia, neutropenia, agranulocytosis, anaemia, macrocytic anaemia, impaired renal function, stomatitis. These should be confirmed against the Health Canada package insert.
- Drug Interactions: 100 interactions were identified. Examples from the first 20 listed:
- Major: deferiprone, samarium (153Sm) lexidronam
- Moderate: NSAIDs (acetylsalicylic acid, ibuprofen, flurbiprofen, diclofenac, ketorolac), salicylates, zidovudine, chloramphenicol, pyrimethamine, glucarpidase, palifermin, roflumilast, naltrexone, sapropterin, strontium-89 chloride, tetanus toxoid
- Minor: topical dapsone
NSAID and salicylate combinations are notable because they may reduce renal clearance of antifolates.
Package insert warnings and contraindications were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence consists of one single-arm phase II study from 2007 with no reported efficacy outcomes in the available data, plus a general review, and there are no registered trials. The class rationale versus pemetrexed is credible, but pemetrexed-based regimens and immunotherapy combinations remain the established comparators. The highest-scoring predictions (adenomatoid tumour, multiple sclerosis) lack any supporting rationale.
To proceed, the following is needed:
- Retrieve the efficacy results (response rate, survival) from the phase II mesothelioma study, with histology-specific data if available
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Comparison against pemetrexed-based and immunotherapy regimens
- A safety monitoring plan covering myelosuppression, mucositis, renal function and folate/B12 supplementation
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.