Bleomycin A2
Also known as: Blenoxane, Bleocin, Bleomycin A2, Bleomycin sulfate, Bleomycin sulfate (major component), BLM A2, NSC-125066
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Summary
Bleomycin A2 is a glycopeptide antibiotic that also functions as an antineoplastic agent. It is administered by injection (intravenous, intramuscular, subcutaneous, intracavitary or intratumoral) and is approved for prescription use. Clinically it is employed in systemic chemotherapy for certain cancers and, more recently, as an intralesional sclerosant for lymphatic and venous vascular malformations.
Mechanism of Action
Bleomycin A2 binds DNA, preferentially at guanine‑cytosine rich regions, and in the presence of Fe(II) and oxygen generates free‑radical species that cleave phosphodiester bonds, producing low‑molecular‑weight DNA fragments. The drug also degrades nucleolar DNA, impairing ribosomal RNA synthesis. Cellular metabolism by bleomycin hydrolase converts the drug to less active metabolites, attenuating its cytotoxicity.
What the Research Shows
Early work demonstrated that bleomycin A2 degrades nucleolar DNA at low micromolar concentrations, with higher doses needed to affect nucleoplasmic DNA, and that this leads to reduced nuclear RNA synthesis in hepatoma cells. Radiolabelled bleomycin binds DNA with high affinity (K≈10^5–10^6 M⁻¹) and can be quantified by radioimmunoassay down to 1 ng/mL. Bleomycin hydrolase metabolises the drug, markedly lowering its cytotoxic potency. A systematic review of intralesional bleomycin for vascular malformations (27 studies, 1325 patients) reported 84–87 % size reduction in lymphatic and venous lesions, with no cases of pulmonary fibrosis and fewer severe adverse events compared with alternative sclerosants. Studies also described the self‑inactivation of Fe(II)‑bleomycin when DNA is absent, indicating a loss of cleavage activity.
Reported Benefits
In oncology, bleomycin A2 provides DNA‑targeted cytotoxicity useful against certain solid tumours and lymphomas. In the context of vascular malformations, intralesional injection yields substantial lesion shrinkage (over 80 % of cases) and appears to cause fewer severe complications than other sclerosants. The ability to monitor drug levels via specific radioimmunoassays facilitates therapeutic drug monitoring.
Limitations of the Evidence
Evidence for intralesional use derives mainly from low‑ to moderate‑quality studies; long‑term outcomes and comparative efficacy remain uncertain. Systemic administration carries a known risk of pulmonary fibrosis, a complication not observed in the reviewed local‑therapy data but still a concern. Most mechanistic insights are from in‑vitro or animal models, and optimal dosing regimens for non‑cancer indications have not been established.
Safety Considerations
Systemic bleomycin is associated with dose‑dependent pulmonary toxicity, skin hyperpigmentation, and mucocutaneous reactions. Intralesional delivery appears to avoid pulmonary fibrosis, but local inflammation, ulceration, and rare severe complications have been reported. Metabolism by bleomycin hydrolase reduces toxicity, yet variability in enzyme activity may influence individual risk. Self‑inactivation of Fe(II)‑bleomycin reduces DNA‑cleaving activity when the drug is not bound to DNA.
How It Is Administered
Bleomycin A2 is supplied as a sulfate salt for injection. It can be given intravenously, intramuscularly, subcutaneously, intracavitarily (e.g., pleural space) or directly into tumours or vascular malformations. Formulations are sterile solutions intended for single‑use administration; the route is selected based on the therapeutic indication.
Routes of Administration
Goals & Uses
- Testicular germ cell tumor treatmentOncologyHigh
- Testicular cancerOncologyHigh
- Hodgkin's lymphoma treatmentOncologyHigh
- Squamous cell carcinoma treatmentOncologyHigh
- Malignant pleural effusion sclerotherapyPalliative OncologyModerate
- Hodgkin lymphomaOncologyHigh
- Non-Hodgkin's lymphoma treatmentOncologyModerate
- Squamous cell carcinoma of head/neckOncologyHigh
Contraindications
- Known hypersensitivity to bleomycinImmuneHigh
- Significant pre-existing pulmonary diseasePulmonaryHigh
- PregnancyPopulationHighPotential fetal risk or insufficient safety data
- Hypersensitivity to bleomycinAllergy/immunologyHigh
- Severe renal impairment (CrCl <25 mL/min)RenalHigh
- Prior severe pulmonary toxicity from bleomycinPulmonaryHigh
- Severe pulmonary fibrosisRespiratoryHigh
Adverse Effects
- Pulmonary fibrosis / pneumonitisPulmonaryUncommon
- Mucocutaneous toxicity (skin thickening, hyperpigmentation, rash)DermatologicCommon
- Pulmonary toxicity (fibrosis, pneumonitis)RespiratoryCommon
- Fever and chillsConstitutionalCommon
- Nausea and vomitingGastrointestinalCommon
- MucositisGastrointestinal / MucosalUncommon
- Skin reactions (hyperpigmentation, erythema)DermatologicCommon
- Raynaud's phenomenonVascularUncommon
- Anaphylactoid reactionsImmunologicUncommon
Drug Interactions
- Live vaccinesHigh
- Supplemental oxygen (high FiO2)High
- Other pulmonary toxic agents (e.g., cyclophosphamide, methotrexate)Moderate
- CisplatinHigh
- Vinca alkaloids (vincristine, vinblastine)Moderate
- High inspired oxygen concentrationsHigh
- Granulocyte colony-stimulating factors (G-CSF)Moderate
Population Constraints
- SmokersLifestyleRelative
- Renal impairmentOrgan ImpairmentRelative
- Elderly patients (≥70 years)AgeRelative
- Pediatric patientsAgeRelative
- Patients requiring general anesthesiaProceduralRelative
- Patients with renal impairmentOrgan ImpairmentRelative
- Elderly patientsAgeRelative
Regulatory Status
- European UnionApprovedApproved: Hodgkin lymphoma, Testicular cancer, Head and neck cancers
- United StatesApprovedApproved: Hodgkin lymphoma, Testicular cancer, Squamous cell carcinoma of head and neck, Gestational trophoblastic diseaseAdministered as bleomycin sulfate injection
- United KingdomApprovedApproved: Hodgkin lymphoma, Testicular cancer, Head and neck cancers
Approved as part of the bleomycin sulfate mixture by the FDA. The mixture contains bleomycin A2 and B2 as primary components. Individual fractions are not separately approved but are covered under the bleomycin sulfate NDA. Cumulative dose limits (typically ≤400 units lifetime) are recommended to reduce pulmonary toxicity risk.
Evidence & Sources
- Journal ArticleLowSeki T, et al.1985-01-01T00:00:00.000000Z
- Journal ArticleLowCrooke ST, et al.1975-01-01T00:00:00.000000Z
- Intralesional Bleomycin Injections for Vascular Malformations: A Systematic Review and Meta-AnalysisJournal ArticleHighHorbach SER, et al.2016-01-01T00:00:00.000000Z
- Journal ArticleLowSebti SM, et al.1989-01-01T00:00:00.000000Z
- Journal ArticleLowRoy SN, et al.1981-01-01T00:00:00.000000Z
- Journal ArticleLowNakamura M, Peisach J1988-01-01T00:00:00.000000Z
Frequently Asked Questions
What medical conditions is bleomycin A2 used to treat?
Bleomycin A2 is approved for systemic chemotherapy of certain cancers, such as Hodgkin lymphoma and testicular cancer, and is employed off‑label as an intralesional sclerosant to shrink lymphatic and venous vascular malformations.
How does bleomycin destroy cancer cells or abnormal vessels?
The drug binds to DNA and, with iron and oxygen, generates free radicals that cut DNA strands. This interferes with replication and RNA synthesis, leading to cell death. When injected into a malformation, the same DNA damage induces fibrosis and reduces lesion size.
What are the main safety concerns with bleomycin?
When given systemically, bleomycin can cause dose‑related lung fibrosis, skin changes, and mucosal irritation. Intralesional use has not shown pulmonary fibrosis in studies but may cause local inflammation or ulceration. Individual differences in bleomycin‑hydrolase activity can affect toxicity.
Is bleomycin administered as a pill or injection?
Bleomycin A2 is only available as an injectable solution. It is delivered intravenously for cancer therapy or directly into lesions (intratumoral, intralesional, intracavitary) for local treatment.
Can doctors monitor bleomycin levels in the blood?
Yes. Radioimmunoassays using antibodies specific for the bleomycinic acid moiety can detect bleomycin concentrations as low as 1 ng/mL, allowing clinicians to measure drug levels in serum.
What is Bleomycin A2?
Bleomycin A2 is a glycopeptide antibiotic that also functions as an antineoplastic agent. It is administered by injection (intravenous, intramuscular, subcutaneous, intracavitary or intratumoral) and is approved for prescription use. Clinically it is employed in systemic chemotherapy for certain cancers and, more recently, as an intralesional sclerosant for lymphatic and venous vascular malformations.
What is Bleomycin A2 used for?
Bleomycin A2 is educationally associated with: Testicular germ cell tumor treatment, Testicular cancer, Hodgkin's lymphoma treatment, Squamous cell carcinoma treatment, Malignant pleural effusion sclerotherapy, Hodgkin lymphoma, Non-Hodgkin's lymphoma treatment, Squamous cell carcinoma of head/neck. Educational only — not medical advice.
How is Bleomycin A2 administered?
Recorded routes of administration: Intracavitary, Intramuscular, Intratumoral, Intravenous, Subcutaneous.
What are the potential side effects of Bleomycin A2?
Reported adverse effects include: Pulmonary fibrosis / pneumonitis, Mucocutaneous toxicity (skin thickening, hyperpigmentation, rash), Pulmonary toxicity (fibrosis, pneumonitis), Fever and chills, Nausea and vomiting, Mucositis, Skin reactions (hyperpigmentation, erythema), Raynaud's phenomenon, Anaphylactoid reactions. This list is not exhaustive — consult a qualified clinician.
Who should avoid Bleomycin A2?
Recorded contraindications: Known hypersensitivity to bleomycin, Significant pre-existing pulmonary disease, Pregnancy, Hypersensitivity to bleomycin, Severe renal impairment (CrCl <25 mL/min), Prior severe pulmonary toxicity from bleomycin, Severe pulmonary fibrosis. Consult a qualified clinician before use.