Vorinostat
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
Vorinostat: Primary cutaneous B-cell lymphoma
One-Sentence Summary
Vorinostat (ZOLINZA) is a histone deacetylase (HDAC) inhibitor marketed in Canada. The TxGNN model predicts it may be effective for primary cutaneous B-cell lymphoma, but no study in the data compiled for this report directly examines this disease; the supporting material consists of 4 early-phase clinical trials in broader populations and 1 preclinical publication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Primary cutaneous B-cell lymphoma |
| TxGNN Prediction Score | 0.9921 |
| 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 general knowledge of the drug class, vorinostat is an HDAC inhibitor (class I/II). It promotes acetylation of histones and other proteins, which can lead to cell-cycle arrest and apoptosis in lymphoid cancers.
A preclinical study in mantle cell lymphoma, an aggressive B-cell neoplasm, showed that vorinostat induces apoptosis by acetylating the promoters of proapoptotic BH3-only genes. This makes it biologically plausible that vorinostat could act in other B-cell lymphomas.
However, this is an inference from a different B-cell lymphoma and a general drug-class mechanism. No data are specific to primary cutaneous B-cell lymphoma. The high TxGNN score (0.9921) is a computational prediction only and is not evidence of clinical benefit.
Clinical Trial Evidence
None of these trials studies primary cutaneous B-cell lymphoma specifically. They offer general safety, dosing and combination information only.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01567709 | Phase 1 | Completed | 34 | Alisertib plus vorinostat in relapsed Hodgkin, B-cell non-Hodgkin and peripheral T-cell lymphomas; combination safety and dose finding, no efficacy signal for the cutaneous subtype |
| NCT00499811 | Phase 1 | Completed | 15 | Vorinostat safety and dosing in solid tumours and lymphomas with liver dysfunction |
| NCT00045006 | Phase 1 | Completed | Not reported | Oral vorinostat in advanced solid tumours and haematological malignancies; general safety and pharmacokinetics |
| NCT01789255 | Phase 2 | Completed | 12 | Vorinostat with tacrolimus and methotrexate to prevent graft-versus-host disease after stem cell transplant; not a lymphoma treatment study |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21652541 | 2011 | Preclinical/in vitro | Clin Cancer Res | Vorinostat induces apoptosis in mantle cell lymphoma through acetylation of proapoptotic BH3-only gene promoters |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02327619 | ZOLINZA | Not listed | Not listed |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (HDAC inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions (thrombocytopenia and anaemia appear among the recorded contraindicated conditions) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver and renal function, electrolytes and glucose |
| Handling Protection | Follow local cytotoxic/hazardous drug handling regulations |
Safety Considerations
- Contraindicated conditions (relations recorded in the drug-disease data, not label text): long QT syndrome (including familial), liver disease, gallbladder disease, thrombocytopenia, anaemia (including macrocytic), hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, potassium deficiency, hypercalcaemia, nephrocalcinosis, phosphorus metabolism disease, pulmonary embolism and diarrhoeal disease.
- Drug Interactions: 61 interactions are recorded. The listed ones are all of Moderate level and mostly involve glucose-lowering agents, for example acarbose, metformin, pioglitazone, glimepiride, glipizide, glyburide, insulin, semaglutide, exenatide and the SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin). Blood glucose should be monitored when these are combined.
Package insert warnings and contraindications were not available in the data compiled for this report; please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: No trial or publication in the data directly studies primary cutaneous B-cell lymphoma, so the evidence level is L5. The high model score and the preclinical B-cell lymphoma data support only biological plausibility.
To proceed, the following is needed:
- Studies (preclinical or clinical) that directly address primary cutaneous B-cell lymphoma
- Confirmed mechanism of action data
- Health Canada package insert warnings and contraindications
- Review of the glucose-related interactions and the QT, hepatic and haematological risks for the target population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.