Lomustine
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Lomustine: From Undocumented Original Indication to Lymphosarcoma
One-Sentence Summary
Lomustine (CCNU, DrugBank DB01206) is a nitrosourea alkylating-agent chemotherapy drug; its original approved indication is not documented in the current evidence pack, and the drug is not currently marketed in this jurisdiction. The TxGNN model predicts strong relevance to Lymphosarcoma, and this pairing is already supported by 17 clinical trials and 20 publications, much of which reflects lomustine’s long-established international use in lymphoma-directed chemotherapy regimens rather than a purely novel signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not documented in available data (drug not currently marketed in this jurisdiction) |
| Predicted New Indication | Lymphosarcoma |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L2 |
| US Market Status | ✗ Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for lomustine is not available in this evidence pack (data gap DG002). Based on the literature retrieved within this pack itself, lomustine (CCNU) is a nitrosourea alkylating agent — the same pharmacologic class as BCNU and methyl-CCNU — noted for its lipophilicity and ability to cross the blood-brain and hemo-meningeal barriers, which historically made it a mainstay for CNS-penetrant chemotherapy (PMID 782694, PMID 1470749).
This class-level mechanism is directly relevant to lymphosarcoma: alkylating agents damage DNA in rapidly dividing lymphoid cells, and nitrosoureas in particular have been used for decades in Hodgkin’s disease and non-Hodgkin lymphoma (NHL) regimens — including LOPP, LEMP, CAMP, PACET, and CIBO-P — several of which are represented in the literature and trial evidence below. The predicted indication therefore does not represent a mechanistically novel hypothesis so much as a re-confirmation of a well-documented, if not currently regulatory-filed, clinical use pattern.
Because original indication and regulatory history are undocumented in this jurisdiction (market status: 未上市, 0 licenses), the primary uncertainty is not mechanistic plausibility but local regulatory and safety documentation — this is captured as a Blocking-severity data gap (DG001) below.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01775475 | Phase 2 (Randomized) | Completed | 7 | RCT comparing IV CHOP vs. oral chemotherapy (incl. lomustine, etoposide, procarbazine) in HIV-associated NHL, Sub-Saharan Africa |
| NCT00049439 | Phase 2 | Completed | 54 | Dose-modified oral lomustine + etoposide + cyclophosphamide + procarbazine in AIDS-related non-Hodgkin lymphoma (US and Africa) |
| NCT00074191 | Phase 2 | Completed | 1 | Methotrexate, procarbazine, lomustine (MPC) ± intraventricular/intra-ocular chemo for primary CNS lymphoma |
| NCT00003114 | Phase 2 | Completed | 5 | Oral lomustine, etoposide, cyclophosphamide, procarbazine for stage IIB–IV AIDS-related Hodgkin’s disease |
| NCT00989352 | Phase 2 | Unknown | 56 | Rituximab + high-dose methotrexate + lomustine + procarbazine, then maintenance, in elderly primary CNS lymphoma |
| NCT00003113 | Phase 2 | Terminated | 6 | Oral combination chemotherapy + G-CSF in elderly intermediate/high-grade NHL |
| NCT00003929 | Phase 2 | Withdrawn | 0 | Lomustine, procarbazine, filgrastim + radiation for AIDS-related and immunocompetent primary CNS lymphoma |
| NCT00317408 | N/A | Unknown | 96 | Combination chemotherapy + total-body irradiation + stem cell transplant for relapsed anaplastic large cell lymphoma (childhood) |
| NCT05518383 | Phase 4 | Recruiting | 300 | B-cell mature NHL treatment protocol for pediatric/adolescent patients, evaluating MRD and risk stratification |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 348294 | 1978 | RCT (CALGB) | Cancer | Randomized comparison of CCNU vs. methyl-CCNU in advanced Hodgkin’s disease, lymphosarcoma, and reticulum cell sarcoma |
| 21303800 | 2011 | Pilot Trial | Annals of Oncology | Rituximab + methotrexate + procarbazine + lomustine (R-MCP) for primary CNS lymphoma in elderly patients |
| 15803492 | 2005 | Clinical Trial | Cancer | Lomustine + ifosfamide + bleomycin + vincristine + cisplatin (CIBO-P) for refractory/recurrent aggressive NHL |
| 2259920 | 1990 | Phase II Study | Seminars in Oncology | Lomustine, cytarabine, mitoxantrone, prednisone (CAMP) for doxorubicin-resistant intermediate/high-grade NHL |
| 8422281 | 1993 | Clinical Study | European J of Cancer | Prednisolone, cytarabine, lomustine, etoposide, thioguanine (PACET) for relapsed/refractory NHL |
| 8436213 | 1993 | Clinical Study | European J of Haematology | Lomustine, etoposide, methotrexate, prednisone (LEMP) for relapsed/refractory NHL |
| 10711848 | 1999 | Clinical Study | Drugs | Oral lomustine, etoposide, cyclophosphamide, procarbazine regimen in AIDS-related lymphoproliferative malignancies (38 patients) |
| 30197327 | 2018 | Retrospective | J of Cancer Research and Therapeutics | Lomustine-containing LACE conditioning regimen before autologous HSCT in refractory/relapsed lymphoma |
| 35999255 | 2022 | Retrospective | Scientific Reports | Comparison of lomustine-containing CEAC vs. BEAM vs. IEAC conditioning before ASCT in peripheral T-cell lymphoma |
| 33336792 | 2021 | Case Series | British J of Haematology | DECC (dexamethasone, etoposide, chlorambucil, lomustine) oral regimen in relapsed/refractory diffuse large B-cell lymphoma |
US Market Information
Currently no marketing authorization is on file for this jurisdiction (Market status: 未上市 / Not Marketed; total licenses: 0).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Nitrosourea alkylating agent) |
| Myelosuppression Risk | High — nitrosoureas cause delayed, cumulative, dose-limiting myelosuppression; the evidence pack itself includes a case of hemorrhagic diathesis and bone marrow aplasia following lomustine overdose (PMID 31062418) |
| Emetogenicity Classification | Moderate to High (single oral alkylating-agent dosing) |
| Monitoring Items | CBC with differential (delayed nadir, typically 4–6 weeks post-dose), pulmonary function (nitrosourea-associated lung toxicity is described in the retrieved literature, PMID 1470749), renal and hepatic function |
| Handling Protection | Cytotoxic drug handling precautions required per standard oral chemotherapy protocols |
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: While the drug-disease pairing has reasonable supporting evidence (L2 — one completed randomized Phase 2 trial plus a substantial body of historical lymphoma-chemotherapy literature), the evidence pack has a Blocking-severity data gap (DG001): TFDA label warnings and contraindications are entirely undocumented, which by definition prevents even a preliminary (S1) safety assessment. The drug also has no marketing history in this jurisdiction, so local safety and dosing precedent cannot be assumed.
To proceed, the following is needed:
- TFDA/local label PDF for lomustine, including warnings and contraindications (DG001, Blocking)
- Confirmed mechanism-of-action and original-indication data from DrugBank or an equivalent regulatory source (DG002, High)
- A formal drug-drug interaction (DDI) review, since the current DDI query returned no results
- Given the high myelosuppression risk of this drug class, a hematological monitoring plan before any S1 safety evaluation can be completed
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.