Lomustine
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Lomustine: From Brain Tumors & Hodgkin's Lymphoma to Lymphosarcoma
One-Sentence Summary
Lomustine (CCNU, DrugBank DB01206) is a lipophilic nitrosourea alkylating agent originally used for primary/metastatic brain tumors and as a component of combination regimens for Hodgkin's lymphoma. The TxGNN model predicts it may be effective for Lymphosarcoma, with 17 clinical trials and 20 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Primary/metastatic brain tumors; Hodgkin's lymphoma (secondary combination therapy) — not present in local licensing data |
| Predicted New Indication | Lymphosarcoma |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L2 |
| Taiwan Market Status | Not Marketed (未上市) |
| Number of Authorizations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in this evidence pack (flagged as a High-severity data gap). Based on known pharmacology, lomustine is a lipophilic nitrosourea that alkylates and cross-links DNA, preferentially affecting rapidly dividing cells including lymphocytes — the same mechanism underlying its established role in Hodgkin lymphoma and non-Hodgkin lymphoma (NHL) combination regimens (e.g., MOPP/LOPP, LEMP, CAMP, PACET).
Lymphosarcoma is an older clinical term largely synonymous with non-Hodgkin lymphoma. Lomustine's original approved use already spans CNS tumors and Hodgkin's disease, both of which share pharmacological and disease-biology proximity to lymphosarcoma (lymphoid malignancy, CNS-penetrant regimens for CNS-involved lymphoma). This places the TxGNN prediction close to an established, adjacent-indication extension rather than a mechanistically novel hypothesis.
Multiple oral combination regimens containing lomustine (CCNU + etoposide + cyclophosphamide + procarbazine; CCNU + vincristine + procarbazine + prednisolone) have been studied specifically in NHL/lymphosarcoma populations, including AIDS-associated lymphoma and primary CNS lymphoma, reinforcing the biological plausibility of this prediction.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01775475 | Phase 2 | Completed | 7 | Randomized trial of CHOP vs. oral chemotherapy (incl. lomustine) with concomitant ART in HIV-associated lymphoma, Sub-Saharan Africa |
| NCT00049439 | Phase 2 | Completed | 54 | Dose-modified oral combination chemotherapy (lomustine, etoposide, cyclophosphamide, procarbazine) in AIDS-related NHL |
| NCT00003114 | Phase 2 | Completed | 5 | Oral combination chemotherapy with lomustine, etoposide, cyclophosphamide, procarbazine in AIDS-related Hodgkin's disease |
| NCT00074191 | Phase 2 | Completed | 1 | MPV regimen (methotrexate, procarbazine, CCNU) ± intra-ocular chemo for primary CNS lymphoma |
| NCT00989352 | Phase 2 | Unknown | 56 | Rituximab + high-dose methotrexate + lomustine + procarbazine, followed by maintenance, in elderly primary CNS lymphoma |
| NCT05518383 | Phase 4 | Recruiting | 300 | Pediatric/adolescent B-cell mature NHL treatment protocol; lomustine inclusion not explicitly confirmed |
| NCT00003113 | Phase 2 | Terminated | 6 | Oral combination chemo + G-CSF in elderly intermediate/high-grade NHL; terminated for poor accrual |
| NCT01989052 | Phase 1 | Terminated | 9 | CTO ± lomustine in bevacizumab-naïve recurrent malignant glioma; efficacy endpoint not lymphoma-specific |
| NCT04402073 | Phase 2 | Terminated | 20 | Personalized risk-adapted therapy for post-pubertal medulloblastoma; disease mismatch (not lymphoma) |
| NCT02551718 | NA | Completed | 34 | Chemosensitivity/genomics-guided treatment in relapsed/refractory acute leukemia; population mismatch |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 348294 | 1978 | RCT (CALGB) | Cancer | Randomized comparison of CCNU vs. methyl-CCNU in Hodgkin's disease, lymphosarcoma, and reticulum cell sarcoma |
| 10711848 | 1999 | Cohort | Drugs | Oral CCNU/etoposide/cyclophosphamide/procarbazine regimen in 38 patients with AIDS-related lymphoproliferative malignancies |
| 8436213 | 1993 | Cohort | European Journal of Haematology | LEMP (lomustine, etoposide, methotrexate, prednisone) in 22 patients with relapsed/refractory NHL |
| 21303800 | 2011 | Cohort | Annals of Oncology | Rituximab + methotrexate/procarbazine/lomustine (R-MCP) pilot trial in elderly primary CNS lymphoma |
| 15803492 | 2005 | Cohort | Cancer | CIBO-P regimen (incl. lomustine) for poor-prognosis refractory/recurrent aggressive NHL |
| 33336792 | 2021 | Cohort | British Journal of Haematology | DECC oral chemotherapy regimen (incl. lomustine) in relapsed/refractory diffuse large B-cell lymphoma |
| 8422281 | 1993 | Cohort | European Journal of Cancer | PACET regimen (incl. lomustine) in 27 patients with relapsed/refractory NHL; 26% complete response |
| 2259920 | 1990 | Phase 2 (Cohort) | Seminars in Oncology | CAMP regimen (lomustine, cytarabine, mitoxantrone, prednisone) in doxorubicin-resistant NHL |
| 30197327 | 2018 | Cohort | Journal of Cancer Research and Therapeutics | LACE (lomustine-containing) conditioning for autologous HSCT in refractory/relapsed lymphoma |
| 35999255 | 2022 | Cohort | Scientific Reports | Comparison of CEAC (lomustine-containing), BEAM, and IEAC conditioning regimens in autologous HSCT for PTCL |
Market Information (Taiwan)
Lomustine currently has no marketing authorization in Taiwan (market status: 未上市 / Not Marketed; 0 licenses on record). No product/dosage form data is available.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Alkylating agent, nitrosourea class) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Please refer to the package insert for safety information. (TFDA package insert warnings/contraindications and drug-interaction data are flagged as an unresolved, Blocking-severity data gap in this evidence pack.)
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Lomustine's mechanism of action and its established, closely related use in Hodgkin lymphoma and CNS lymphoma combination regimens provide strong mechanistic plausibility for lymphosarcoma; evidence includes one completed randomized Phase 2 trial (NCT01775475) and multiple cohort studies, meeting L2 evidence criteria. However, the drug is not currently marketed in Taiwan and safety/labeling data are unresolved.
To proceed, the following is needed:
- TFDA package insert (warnings, contraindications) — currently a Blocking data gap
- Confirmed mechanism of action (MOA) data from DrugBank
- Drug-drug interaction (DDI) profile
- Local regulatory pathway assessment given current "Not Marketed" status in Taiwan
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.