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. The TxGNN model predicts it may be effective for lymphosarcoma, but the evidence level is only L4: the only study that directly addresses lymphosarcoma is a mouse study, while the 10 clinical trials and 20 publications compiled for this report mostly cover related lymphoma subtypes treated with combination regimens, or canine lymphoma.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Lymphosarcoma |
| TxGNN Prediction Score | 0.9990 |
| Evidence Level | L4 |
| India Market Status | Listed in a compiled Indian medicine price dataset (4 of 4) – CDSCO approval status is not included in this data |
| Number of Listed Products | 4 (valid: 4) |
| 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, lomustine is a lipophilic nitrosourea alkylating agent. It damages DNA, and its lipophilicity lets it cross the blood-brain barrier. This property is why it is used in central nervous system tumours and why it is of interest in lymphoid cancers that involve the brain.
Lymphomas are generally sensitive to alkylating agents. Oral lomustine-containing regimens, such as combinations with procarbazine, etoposide and cyclophosphamide, have been tested in AIDS-related non-Hodgkin lymphoma and primary CNS lymphoma. These studies concern lymphoma subtypes treated with multi-drug regimens, so they support the mechanistic plausibility but do not directly show that lomustine works in lymphosarcoma.
The only study that directly names lymphosarcoma is a mouse study of intracranially transplanted lymphosarcoma. Lomustine extended survival 1.6-fold on its own and 3.3-fold when combined with gemcitabine. Veterinary data in canine T-cell lymphoma add supportive but non-human evidence. This 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 |
| NCT00989352 | Phase 2 | Unknown | 56 | Rituximab, high-dose methotrexate, lomustine and procarbazine in primary CNS lymphoma in patients over 65 |
| NCT01775475 | Phase 2 | Completed | 7 | CHOP vs oral chemotherapy including lomustine in HIV-associated lymphoma; very small |
| NCT00003113 | Phase 2 | Terminated | 6 | Oral combination chemotherapy with G-CSF in elderly intermediate- and high-grade non-Hodgkin lymphoma |
| NCT00074191 | Phase 2 | Completed | 1 | Methotrexate, procarbazine and CCNU in primary CNS lymphoma; only 1 patient |
| NCT00003114 | Phase 2 | Completed | 5 | Lomustine, etoposide, cyclophosphamide and procarbazine in AIDS-related Hodgkin’s disease |
| NCT00003929 | Phase 2 | Withdrawn | 0 | Lomustine, procarbazine, filgrastim and radiation in primary CNS lymphoma; no data generated |
| NCT03678883 | Phase 2 | Active, not recruiting | 350 | 9-ING-41 with chemotherapy in refractory cancers; lomustine is not the investigational agent |
None of these trials studies lymphosarcoma by name.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 22888657 | 2012 | Preclinical (mouse) | Voprosy Onkologii | In mice with intracranial lymphosarcoma, lomustine extended lifespan 1.6-fold and gemcitabine plus lomustine 3.3-fold |
| 10711848 | 1999 | Clinical study | 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; lomustine is one of several combination partners with high-dose methotrexate |
| 21303800 | 2011 | Pilot trial | Annals of Oncology | Rituximab, methotrexate, procarbazine and lomustine for elderly primary CNS lymphoma |
| 8436213 | 1993 | Clinical study | Eur J Haematol | LEMP regimen (lomustine, etoposide, methotrexate, prednisone) in 22 patients with relapsed or refractory non-Hodgkin lymphoma |
| 35999255 | 2022 | Retrospective comparison | Scientific Reports | CEAC (lomustine-based) vs BEAM vs IEAC conditioning before stem cell transplant in 52 peripheral T-cell lymphoma patients |
| 28508557 | 2018 | Cohort (canine) | Vet Comp Oncol | LOPP protocol as first-line therapy in dogs with T-cell lymphoma |
| 30117253 | 2018 | Cohort (canine) | Vet Comp Oncol | Modified LOPP chemotherapy in 35 dogs with T-cell lymphoma |
| 28222789 | 2017 | Review (canine) | BMC Vet Res | Appraisal of CCNU for canine cutaneous epitheliotropic lymphoma; no clear consensus on benefit |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Registration No. 27908 | Belustine 40 Capsule (Mediclone Health Care) | Bottle of 10 capsules | Not specified |
| Registration No. 137802 | Moostin 40mg Capsule (Miracalus Pharma) | Strip of 6 capsules | Not specified |
| Registration No. 125974 | Lomat 40mg Capsule (Neon Laboratories) | Strip of 4 capsules | Not specified |
| Registration No. 125072 | Lustine 40mg Capsule (Samarth Life Sciences) | Strip of 4 capsules | Not specified |
All four licences are valid single-ingredient oral capsule products.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (nitrosourea alkylating agent) |
| Myelosuppression Risk | High (delayed myelosuppression with leukopenia and thrombocytopenia is a recognised concern) |
| Emetogenicity Classification | Moderate to high |
| Monitoring Items | CBC with differential and platelets, liver and renal function, pulmonary status |
| Handling Protection | Follow cytotoxic drug handling regulations |
Safety Considerations
- Conditions flagged as contraindicated or of concern: kidney disease, thrombocytopenia, leukopenia, hyperbilirubinemia (including Gilbert syndrome), drug-induced liver injury, pulmonary fibrosis, and active infectious or fungal disease. These come from relation data, not label text.
- Drug Interactions: 172 interactions were identified. Major ones include cimetidine, deferiprone, adalimumab and samarium (153Sm) lexidronam. Moderate ones include mercaptopurine, zidovudine, aldesleukin, alemtuzumab and chloramphenicol. Because of the overlapping myelosuppression and immunosuppression, co-medications need careful review.
Package insert warnings and contraindications for the Indian products are not available in the compiled data. Please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The evidence level is L4. The only study directly addressing lymphosarcoma is a mouse study. The human trials are small, mostly terminated, withdrawn or very small, and cover related lymphoma subtypes in multi-drug regimens, so the specific contribution of lomustine cannot be separated out.
To proceed, the following is needed:
- Human studies that directly address lymphosarcoma with lomustine
- Mechanism of action data
- Package insert warnings and contraindications for the Indian products
- A myelosuppression monitoring and interaction management plan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.