Lomustine
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Lomustine: From CNS Tumors and Hodgkin’s Lymphoma to Lymphosarcoma
One-Sentence Summary
Lomustine (CCNU) is a lipid-soluble nitrosourea alkylating agent historically used as a chemotherapy backbone for brain tumors and Hodgkin’s/non-Hodgkin’s lymphoma combination regimens (its formal original-indication record is a data gap in this evidence pack — the drug is not marketed in Taiwan). The TxGNN model predicts it may be effective for Lymphosarcoma, with 16 clinical trials and 20 publications currently identified, several of which directly test lomustine-containing regimens in lymphoma populations.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not confirmed in this evidence pack (Taiwan: unmarketed, no license records; historically used for CNS tumors/Hodgkin’s lymphoma per background literature) |
| Predicted New Indication | Lymphosarcoma |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L2 |
| Taiwan Market Status | Not marketed (Not Marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available from DrugBank (flagged as a High-severity data gap, DG002). Based on established oncology knowledge reflected throughout the collected evidence, Lomustine (CCNU) is a lipid-soluble nitrosourea alkylating agent capable of crossing the blood-brain barrier and forming DNA/RNA cross-links, and it has long served as a component of combination chemotherapy regimens (e.g., PCV, LOPP, LEMP, DECC, PACET) for CNS tumors and Hodgkin’s/non-Hodgkin’s lymphoma.
Because lymphosarcoma is a lymphoproliferative malignancy closely related to non-Hodgkin’s lymphoma, and lomustine’s cytotoxic alkylating activity is already an accepted partner drug in several NHL and primary CNS lymphoma regimens (LEMP, R-MCP, DECC, PACET, CAMP, CIBO-P), the mechanistic leap from “established lymphoma-adjacent chemotherapy component” to “predicted efficacy in lymphosarcoma” is biologically plausible rather than speculative.
The clinical evidence, however, is dominated by small, older, or non-lymphosarcoma-specific trials (Phase 1/2, N often <60), and a meaningful share of the supporting literature is veterinary (canine/feline) rather than human. This tempers confidence: the mechanistic and combination-regimen rationale is reasonably strong, but a dedicated, adequately powered human lymphosarcoma trial is still lacking.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01989052 | Phase 1/2 | Terminated | 9 | CTO combined with lomustine in recurrent malignant glioma; directly tests lomustine’s role but terminated with very small sample |
| NCT05518383 | Phase 4 | Recruiting | 300 | B-cell mature non-Hodgkin lymphoma treatment protocol in children/adolescents; large validation-style study of existing treatment pathway |
| NCT01775475 | Phase 2 | Completed | 7 | CHOP vs. oral chemotherapy (incl. lomustine-containing regimen) in HIV-associated non-Hodgkin lymphoma; underpowered |
| NCT06816134 | Phase 2 | Recruiting | 48 | RCT of TmBU vs. mBUCY conditioning before allo-HSCT in high-risk/relapsed acute leukemia |
| NCT00049439 | Phase 2 | Completed | 54 | Lomustine + etoposide + cyclophosphamide + procarbazine (CEPP-type) oral regimen in AIDS-related non-Hodgkin lymphoma, US and Africa |
| NCT00003114 | Phase 2 | Completed | 5 | Lomustine + etoposide + cyclophosphamide + procarbazine in AIDS-related Hodgkin’s disease (stage IIB–IV) |
| NCT00989352 | Phase 2 | Unknown | 56 | Rituximab + methotrexate + lomustine + procarbazine, followed by procarbazine maintenance, for primary CNS lymphoma in patients >65 years |
| NCT00074191 | Phase 2 | Completed | 1 | Methotrexate + procarbazine + lomustine ± intraocular chemotherapy for primary CNS lymphoma |
| NCT00003929 | Phase 2 | Withdrawn | 0 | Lomustine + procarbazine + filgrastim + radiotherapy for AIDS-related and immunocompetent primary CNS lymphoma; no data generated (withdrawn) |
| NCT00003113 | Phase 2 | Terminated | 6 | Oral combination chemotherapy + G-CSF in elderly patients with intermediate/high-grade NHL |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 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 for elderly primary CNS lymphoma |
| 33336792 | 2021 | Cohort | British Journal of Haematology | DECC (dexamethasone, etoposide, chlorambucil, lomustine) oral regimen in relapsed/refractory DLBCL |
| 348294 | 1978 | Randomized study | Cancer | CALGB randomized comparison of CCNU vs. methyl-CCNU in advanced Hodgkin’s disease, lymphosarcoma, and reticulum cell sarcoma |
| 30197327 | 2018 | Cohort | Journal of Cancer Research and Therapeutics | Lomustine-containing LACE conditioning for autologous HSCT in refractory/relapsed lymphoma |
| 2259920 | 1990 | Phase 2 | Seminars in Oncology | CAMP (lomustine, cytarabine, mitoxantrone, prednisone) in doxorubicin-resistant intermediate/high-grade NHL; 27% CR |
| 15803492 | 2005 | Phase 2 | Cancer | CIBO-P (lomustine, ifosfamide, bleomycin, vincristine, cisplatin) for refractory/relapsed aggressive NHL |
| 10711848 | 1999 | Cohort | Drugs | Oral lomustine + etoposide + cyclophosphamide + procarbazine in 38 patients with AIDS-related lymphoproliferative malignancy |
| 8422281 | 1993 | Cohort | European Journal of Cancer | PACET (prednisolone, cytarabine, lomustine, etoposide, thioguanine) in 27 patients with relapsed/refractory NHL; 26% CR |
| 22888657 | 2012 | Preclinical | Voprosy Onkologii | Gemcitabine + lomustine combination increased survival 3.3-fold vs. control in mice with intracranial lymphosarcoma LIO-1 |
Taiwan Market Information
Lomustine currently has no marketing authorization in Taiwan (market status: Not marketed, 0 registered licenses). No product/dosage-form/indication records are available to summarize.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (nitrosourea alkylating agent, CCNU class) |
| Myelosuppression Risk | High — delayed and cumulative (class-typical thrombocytopenia/leukopenia nadir around 4–6 weeks post-dose); product-specific TFDA labeling data needed to confirm exact thresholds (see Data Gap DG001) |
| Emetogenicity Classification | Moderate (typical for oral nitrosoureas under standard oncology emetogenicity classification; TFDA-specific data not available) |
| Monitoring Items | CBC with differential (extended monitoring through 6 weeks due to delayed nadir), pulmonary function (nitrosourea-class pulmonary fibrosis risk), hepatic and renal function |
| Handling Protection | Standard cytotoxic drug handling and disposal precautions required |
Safety Considerations
Drug Interactions: 172 interactions on record. Notable Major-level interactions include Cimetidine, Deferiprone, Samarium (153Sm) lexidronam, and Adalimumab; Moderate-level interactions include Naltrexone, Palifermin, Mercaptopurine, Zidovudine, and several immunomodulators/vaccines.
TFDA-specific key warnings and contraindications are not yet available for this drug (data gap, Blocking severity — see DG001); safety review cannot proceed to initial (S1) assessment until this label data is obtained.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The mechanistic and combination-regimen rationale for lymphosarcoma is reasonably supported (Evidence Level L2, multiple lomustine-containing regimens already used in NHL/lymphoma settings), but a Blocking-severity data gap on TFDA warnings/contraindications prevents entry into initial safety assessment, and the drug remains completely unregistered in Taiwan (0 licenses).
To proceed, the following is needed:
- TFDA product label (warnings, contraindications, dosing) — currently a Blocking data gap
- DrugBank/formal mechanism-of-action confirmation
- A dedicated, adequately powered human lymphosarcoma/NHL trial (most current evidence is repurposed from adjacent indications, small-N, or veterinary)
- Assessment of import/named-patient access pathways given unmarketed 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.