Lomustine
| Evidence Level: L4 | Predicted Indications: 3 |
Table of Contents
Lomustine: Lymphosarcoma
One-Sentence Summary
Lomustine is an oral nitrosourea alkylating agent that crosses the blood-brain barrier and is marketed in Canada as CEENU. The TxGNN model predicts it may be effective for lymphosarcoma (lymphosarcoma), with a prediction score of 0.9990. Evidence is at Level L4: the only study that addresses lymphosarcoma itself is a mouse study, while the 10 listed clinical trials and the remaining publications concern lymphoma subtypes or combination regimens.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Lymphosarcoma |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L4 |
| Canada Market Status | Marketed (marketed DINs: 2 of 2) |
| Number of DINs | 2 (marketed: 2) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for lomustine are not available in the data compiled for this report. From general pharmacology, lomustine is a lipophilic nitrosourea alkylating agent. It damages DNA by cross-linking, which is most harmful to rapidly dividing cells, and it can reach the central nervous system.
These properties make lymphoid malignancies a plausible target, particularly lymphomas involving the brain and spinal cord. Lomustine is already used as part of combination regimens, including oral CCNU-based regimens for AIDS-related lymphoma, and in canine lymphoma protocols such as LOPP (lomustine, vincristine, procarbazine, prednisolone). Its activity in lymphoma has also been explored in primary CNS lymphoma regimens.
The caveat is that almost all of this work involves lomustine as one component of a multi-drug regimen, or involves animals, so the contribution of lomustine alone to lymphosarcoma cannot be separated out. The single study of lymphosarcoma itself (PMID 22888657) is a mouse model, which is why the evidence level is capped at L4.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00049439 | Phase 2 | Completed | 54 | Dose-modified oral lomustine, etoposide, cyclophosphamide and procarbazine in AIDS-related non-Hodgkin lymphoma |
| NCT01775475 | Phase 2 | Completed | 7 | CHOP vs oral chemotherapy (including lomustine) in HIV-associated lymphoma; very small enrollment |
| NCT00989352 | Phase 2 | Unknown | 56 | Rituximab, high-dose methotrexate, lomustine and procarbazine in primary CNS lymphoma over age 65 |
| NCT00074191 | Phase 2 | Completed | 1 | Methotrexate, procarbazine and CCNU for primary CNS lymphoma; only one patient enrolled |
| NCT00003114 | Phase 2 | Completed | 5 | Oral lomustine-based combination in AIDS-associated Hodgkin disease; very small enrollment |
| NCT00003113 | Phase 2 | Terminated | 6 | Oral combination chemotherapy with G-CSF in elderly patients with non-Hodgkin lymphoma; stopped early |
| NCT00003929 | Phase 2 | Withdrawn | 0 | Lomustine, procarbazine, filgrastim and radiation in primary CNS lymphoma; never enrolled |
| NCT03678883 | Phase 2 | Active, not recruiting | 350 | 9-ING-41 alone or with chemotherapy in refractory cancers; lomustine is one possible partner, so relevance is indirect |
| NCT00317408 | Not applicable | Unknown | 96 | Relapsed anaplastic large cell lymphoma in children; lomustine’s role is uncertain |
| NCT01989052 | Phase 1 | Terminated | 9 | Carboxyamidotriazole orotate with lomustine in recurrent glioma; not a lymphoma study |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22888657 | 2012 | Preclinical | Voprosy onkologii | In mice with transplanted lymphosarcoma, lomustine extended lifespan 1.6-fold, and combined with gemcitabine 3.3-fold |
| 10711848 | 1999 | Cohort | Drugs | Oral lomustine, etoposide, cyclophosphamide and procarbazine regimen in 38 patients with AIDS-related non-Hodgkin lymphoma |
| 17134114 | 2006 | Review | Neurosurgical Focus | Chemotherapy for primary CNS lymphoma; high-dose methotrexate is most effective, with lomustine among combination partners |
| 21303800 | 2011 | Pilot trial | Annals of Oncology | Rituximab with methotrexate, procarbazine and lomustine in elderly patients with primary CNS lymphoma |
| 8436213 | 1993 | Clinical series | European Journal of Haematology | LEMP (lomustine, etoposide, methotrexate, prednisone) in 22 patients with relapsed or refractory non-Hodgkin lymphoma |
| 35999255 | 2022 | Retrospective | Scientific Reports | CEAC (lomustine-containing) conditioning before autologous transplant in 52 patients with peripheral T-cell lymphoma |
| 28508557 | 2018 | Cohort (canine) | Veterinary and Comparative Oncology | LOPP protocol as first-line treatment of canine T-cell lymphoma |
| 30117253 | 2018 | Cohort (canine) | Veterinary and Comparative Oncology | Modified LOPP in 35 dogs with T-cell lymphoma |
| 28222789 | 2017 | Review (canine) | BMC Veterinary Research | No clear consensus on the benefit of lomustine for canine cutaneous T-cell lymphoma |
| 2222244 | 1990 | Clinical series | Archives of Neurology | Procarbazine, lomustine and vincristine adjuvant therapy in 10 patients with primary CNS lymphoma |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 00360422 | CEENU | Not specified | Not specified |
| 00360430 | CEENU | Not specified | Not specified |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (nitrosourea alkylating agent) |
| Myelosuppression Risk | High; delayed and cumulative bone marrow suppression (thrombocytopenia, leukopenia) is characteristic of nitrosoureas |
| Emetogenicity Classification | Moderate to high |
| Monitoring Items | Complete blood count with differential, liver and renal function, pulmonary function |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Please also refer to the package insert warnings and precautions.
Safety Considerations
- Contraindication-related conditions (not label text): the data compiled for this report flag kidney disease, thrombocytopenia, leukopenia, hyperbilirubinemia (including Gilbert syndrome), drug-induced liver injury, pulmonary fibrosis, and fungal or other infectious diseases. These should be confirmed against the Health Canada product monograph.
- Drug Interactions: 100 interactions were found. Major-level examples are cimetidine, deferiprone, samarium (153Sm) lexidronam and adalimumab. Moderate-level examples include mercaptopurine, zidovudine, chloramphenicol, aldesleukin, alemtuzumab and asparaginase. Naltrexone and palifermin are also listed as moderate; levofloxacin is minor.
The package insert warnings and contraindications for the Canadian products have not yet been reviewed. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (0.9990), and lomustine is plausible mechanistically and is used within lymphoma combination regimens. However, the only study of lymphosarcoma itself is a mouse model, and the clinical data are small trials or retrospective series in which lomustine cannot be separated from its combination partners. This places the evidence at L4.
To proceed, the following is needed:
- Review of the Health Canada product monograph for warnings and contraindications
- Mechanism-of-action data for lomustine
- Clinical data in which lomustine’s contribution to lymphoma outcomes is separable from companion drugs
- A safety and myelosuppression monitoring plan, given the high haematological toxicity of nitrosoureas
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.