Bleomycin
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Bleomycin: From Lymphoma and Head and Neck Cancer to Cauda Equina Neoplasm
One-Sentence Summary
Bleomycin is a cytotoxic anticancer antibiotic, originally used for Hodgkin and non-Hodgkin lymphomas, Langerhans cell histiocytosis and head and neck cancer. The TxGNN model ranks cauda equina neoplasm as its top predicted new indication, but this prediction rests on no clinical trials and 1 indirect publication. Among the other top-10 predictions, the best-supported is reticulum cell sarcoma (a historical term for non-Hodgkin lymphoma), with 11 clinical trials and 20 publications. It largely overlaps with bleomycin's existing lymphoma uses.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Lymphomas (Hodgkin and non-Hodgkin), Langerhans cell histiocytosis, head and neck cancer (the Singapore licence record contains no indication text) |
| Predicted New Indication | Cauda equina neoplasm |
| TxGNN Prediction Score | 99.30% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 1 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Bleomycin is a cytotoxic antibiotic that is generally known to cause DNA single- and double-strand breaks. Its efficacy in lymphoma is established, and this mechanism may plausibly apply to germ cell tumours.
For cauda equina neoplasm, the only linked paper describes radiation therapy for relapsed CNS germinoma after chemotherapy that included carboplatin, etoposide and bleomycin (PEB). This is indirect evidence. Bleomycin also penetrates the blood-brain and blood-spinal cord barriers poorly, which weakens the rationale for a tumour in this location.
Other predictions in the top 10 show different strengths:
- Reticulum cell sarcoma (rank 3, score 99.14%): this is the strongest-supported prediction. The term is historical for diffuse large B-cell/non-Hodgkin lymphoma, so it largely overlaps with bleomycin's approved lymphoma uses. This limits its repurposing novelty.
- Adult astrocytic tumour (rank 2, score 99.28%): older studies of bleomycin in glioma exist, but there are no controlled efficacy data.
- Interdigitating dendritic cell sarcoma (rank 8, score 98.63%): several case reports describe remission after ABVD chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine).
- Primary pulmonary lymphoma, pulmonary blastoma, small cell lung carcinoma, well-differentiated fetal adenocarcinoma of the lung, acute lymphoblastic leukaemia and astrocytoma (excluding glioblastoma): evidence is absent, indirect or limited to case reports. Bleomycin's pulmonary toxicity is an added concern for lung diseases.
Clinical Trial Evidence
No clinical trials are registered for the top-ranked prediction, cauda equina neoplasm. Currently no related clinical trials registered.
The trials below were linked to the lymphoma-type predictions (reticulum cell sarcoma and interdigitating dendritic cell sarcoma). Almost all test bleomycin-containing combinations, so bleomycin's individual contribution cannot be isolated.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00002565 | Phase 3 | Completed | 61 | Alternating triple therapy vs CHOP in intermediate-grade and immunoblastic lymphoma |
| NCT00002835 | Phase 3 | Completed | 116 | Early intensification vs alternating triple therapy in poor-prognosis lymphoma |
| NCT00005867 | Phase 3 | Completed | 310 | CHOP vs PMitCEBO in good-risk aggressive non-Hodgkin lymphoma |
| NCT00003815 | Phase 3 | Unknown | Not reported | High-dose chemotherapy/radiotherapy with autologous transplant in high-grade non-Hodgkin lymphoma |
| NCT00003110 | Phase 2 | Completed | 5 | 72-hour continuous infusion bleomycin as salvage therapy in AIDS-related and immunocompetent non-Hodgkin lymphoma |
| NCT00002571 | Phase 2 | Completed | 52 | ProMACE-CytaBOM with antiviral therapy and G-CSF in AIDS-related lymphoma |
| NCT00002524 | Phase 2 | Completed | 46 | Combination chemotherapy pilot in AIDS-related lymphoma |
| NCT00002657 | Phase 2 | Completed | 20 | ProMACE-CytaBOM with immunosuppression reduction and interferon in post-cardiac transplant lymphoproliferation |
| NCT00032149 | Phase 1/2 | Unknown | 30 | PMitCEBO plus G-CSF in good-prognosis HIV-related lymphoma |
| NCT00031902 | Phase 1 | Unknown | Not reported | Rituximab plus PVB chemotherapy in poor-prognosis HIV-related non-Hodgkin lymphoma |
Literature Evidence
The only paper linked to cauda equina neoplasm is listed first. The remaining rows are the most relevant papers for the other predictions.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 9440744 | 1998 | Cohort | J Clin Oncol | Radiation therapy to salvage relapsed CNS germinoma after primary PEB chemotherapy (carboplatin, etoposide, bleomycin); indirect for cauda equina neoplasm |
| 14962711 | 2004 | Trial analysis | Eur J Cancer | Long-term efficacy of the bleomycin-containing CHVmP/BV regimen in 936 patients across three randomised EORTC trials in aggressive non-Hodgkin lymphoma |
| 4109401 | 1972 | Clinical study | Br Med J | Bleomycin alone in 54 patients with Hodgkin disease, 17 with lymphosarcoma, 22 with reticulum cell sarcoma and 7 with mycosis fungoides; 29% of Hodgkin patients remitted |
| 27888880 | 2016 | Review | Hematol Oncol Clin North Am | Optimising outcomes in primary mediastinal B-cell lymphoma |
| 6164465 | 1981 | Randomised trial | Cancer | 118 patients with grade III-IV astrocytoma; confirmed the value of postoperative irradiation but found no survival benefit from adding bleomycin |
| 12416544 | 2002 | Phase I trial | J Neurooncol | Continuous intratumoral bleomycin infusion for recurrent glioblastoma |
| 22783364 | 2012 | Case report | Korean J Hematol | Successful ABVD treatment of disseminated interdigitating dendritic cell sarcoma |
| 26106005 | 2015 | Case report | J Clin Exp Hematop | Complete remission of systemic skin interdigitating dendritic cell sarcoma after ABVD |
| 18827617 | 2008 | Case report | J Thorac Oncol | Biphasic pulmonary blastoma with germ cell differentiation; markers responded to four cycles of bleomycin, etoposide and cisplatin, but the tumour did not regress |
| 2414409 | 1985 | Clinical study | J Clin Oncol | Bleomycin, etoposide and cisplatin in 53 patients with advanced non-small cell lung cancer; 44% response rate (not small cell) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN08426P | DBL Bleomycin Sulfate for Injection 15000 iu/vial (Zydus Hospira Oncology Private Limited) | Injection, powder, for solution | Not listed in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (antitumour antibiotic) |
| Myelosuppression Risk | Generally low; the literature describes bleomycin as marrow-sparing, but it is usually given in combination regimens that cause myelosuppression |
| Emetogenicity Classification | Low |
| Monitoring Items | Pulmonary function and chest imaging (pulmonary toxicity is the key concern), CBC, liver and renal function; fever or hyperpyrexic reactions after the first doses |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Pulmonary toxicity: the literature linked to this report repeatedly describes bleomycin pulmonary toxicity, including interstitial pneumonitis, a risk that increases with age, and enhanced toxicity when combined with radiotherapy. This matters particularly for any lung-related use.
- Hyperpyrexic reaction: a case report describes fatal hyperpyrexia in a lymphoma patient.
- Drug interactions: 100 interactions were identified. The only one with a classified level is levofloxacin (Minor); the rest are unclassified. Examples include pantoprazole, palonosetron, lactulose, aprepitant, morphine, omeprazole, vancomycin, prednisone, hydrocortisone and ondansetron.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for the full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The top-ranked prediction, cauda equina neoplasm, has no clinical trials and only one indirect paper. Poor penetration of the blood-brain and blood-spinal cord barriers further weakens the case. The best-supported prediction, reticulum cell sarcoma, is essentially non-Hodgkin lymphoma, which bleomycin already treats, so it offers little repurposing novelty. Bleomycin's contribution within multi-drug regimens also cannot be isolated.
To proceed, the following is needed:
- Package insert warnings and contraindications from the Singapore regulator, as safety screening cannot proceed without them
- Approved indication text for the Singapore licence
- Mechanism of action data
- For CNS or spinal tumours: evidence on drug delivery across the blood-brain and blood-spinal cord barriers, and any direct clinical data for cauda equina neoplasm
- For lymphoma-type predictions: confirmation of how the predicted disease differs from bleomycin's existing lymphoma uses
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.