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Bleomycin: Chemotherapie of Germ Cell Tumors
Mechanism of Action of Bleomycin
Bleomycin is a cytostatic agent (glycopeptid antibiotic) from the bacterium Streptomyces verticillus. Bleomycin binds specifically to DNA, causes DNA strand breaks and leads to apoptosis. In high concentrations, bleomycin acts as an endonuclease and cleaves the DNA.
Urologic Indications for Bleomycin
Metastatic germ cell tumors of the testes or extragonadal germ cell tumors.
Pharmacokinetics of Bleomycin
Renal elimination half-life initially 24 min, then 2–4 h. In renal insufficiency, a dosage adjustment is necessary.
Side Effects of Bleomycin
Pulmonary Side Effects:Bleomycin may cause a subacute or chronic pneumonia (interstitial plasmacellular pneumonia) with fibrosis. In 1% of treated patients, pulmonary side effects are severe and potentially leathal. Risk factors: advanced age, pulmonary disease and cumulative bleomycin dosage more than 300 mg.
Signs and symptoms of bleomycin pneumonia: cough, shortness of breath and fever. Diagnosis is achieved with chest x-ray, CT-thorax and pulmonary function testing. At the first signs of interstitial pneumonia, further bleomycin treatment is contraindicated.
Other Side-Effects of Bleomycin
- Skin: eruptions of the skin, nail changes, hair loss, skin necrosis
- Chills and fever, especially for first response, is typical for bleomycin. A lethal hyperthermia is possible, especially in lymphoma patients. A test dose of 1 mg, followed by an observation of 4 hours, is recommended prior to first therapeutic dosage.
- Gastrointestinal tract: nausea and vomiting, diarrhea, loss of appetite
- Joint and muscle pain
- Raynaud's syndrome, mycardial infarction or cerebrovascular events possible
Interactions with Bleomycin
Avoide nephrotoxic or myelosuppressive agents. No live vaccines.
Contraindications of Bleomycin
- Bleomycin intolerance
- Lung fibrosis
- Relative contraindications (depending on the severity): restrictive or obstructive lung disease, lung irradiation, kidney or liver insufficiency.
Dosage of Bleomycin
Bleomycin (15 mg/m2) on day 1, 8, and 15 as a i.v. bolus. One cycle of PEB regimen lasts 21 days. Maximum dosage is 3–4 cycles.
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Deutsche Version: Bleomycin