Indications
Contraindications
Pharmacology
- Bleomycin is an Antibiotic Derived from Streptomyces Verticillus: in 1962
Anti-Neoplastic Mechanisms
- Direct Cytotoxic Effect
- Prevention of Tumor Angiogenesis
- Stimulation of Cytokine Production
- Free Radical generation Via Formation of Complex Between Ferrous Iron and Oxygen: this mechanism probably plays a role in the synergism between bleomycin and oxygen (which may persist for months-years after bleomycin administration)
Myelosuppression
- Bleomycin is Not Considered Myelosuppressive
Bleomycin Pulmonary Toxicity
- Likely Involves Oxidative Injury in the Lung: as bleomycin hydrolase (the enzyme which inactivates bleomycin) is not active in the lung or skin
- Activation of Alveolar Macrophages
- Inflammatory Cytokines
Administration
- IV: xxx
- Intrapleural (For Malignant Pleural Effusion)
Adverse Effects
Allergic/Immunologic Adverse Effects
Anaphylaxis-Like Syndrome (see Anaphylaxis, [[Anaphylaxis]])
- Epidemiology: occurs in 1% of lymphoma patients treated with bleomycin
- Clinical
- Usually occurs after first or second dose
- Onset: may be immediate or delayed (for several hours)
Cardiovascular Adverse Effects
Acute Chest Pain During Bleomycin Infusion (see Chest Pain, [[Chest Pain]])
- Epidemiology: occurs in 3% of cases
- Physiology: due to pleuropericarditis
Dermatologic Adverse Effects
Skin Toxicity
- Epidemiology: usually a late manifestation, developing in the 2nd-3rd week of treatment (after patient receives 150-200 U of bleomycin)
- Related to cumulative dose
- Clinical
Gastrointestinal Adverse Effects
Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
Weight Loss
- Epidemiology: may persist after cessation of bleomycin
Otolaryngologic Adverse Effects
Stomatitis (see Stomatitis, [[Stomatitis]])
Pulmonary Adverse Effects
General Comments
- Prevalence: bleomycin-inducred lung toxicity is the most prevalent and best understood chemotherapy-induced lung disease
- Incidence: between 0-46% of Bleomycin-treated patients develop lung toxicity
- By PFT’s and CXR: 20% of Bleomycin-treated patients develop lung toxicity
- Average Latency Between Bleomycin Administration and Onset of Lung Toxicity: 4 months
- Risk Factors for Bleomycin Lung Toxicity
- Age >70 y/o: known risk factor
- High FIO2 Administration (in OR, PACU, etc.): synergistically increases incidence of bleomycin lung toxicity
- Although duration of risk after receiving bleomycin is not known (risk may extend for years), bleomycin within the last 6 months probably poses greatest risk
- Toxicity associated with oxygen use begins about 18 hrs after exposure to oxygen (and may progress to acute lung injury-ARDS)
- Concomitant Cyclophosphamide Administration (see Cyclophosphamide, [[Cyclophosphamide]]): increases risk of bleomycin lung toxicity
- Concomitant Granulocyte Colony Stimulating Factor (GSCF) Administration (see Granulocyte Colony Stimulating Factor, [[Granulocyte Colony Stimulating Factor]]): controversial as to whether this increases risk of bleomcyin lung toxicity
- Cumulative Bleomycin Dose: increased risk of toxicity with cumulative dose >450 U
- Cumulative Dose >550 U: death rate increases to 10%
- However, doses as low as 50 U may be toxic, in conjunction with other risk factors
- Pediatric Age Group
- 70% of children treated with Bleomycin for rhabdomyosarcoma developed pumonary toxicity in one study
- Pre-Existing Lung Disease
- Prior or Concomitant Thoracic Radiation Therapy: markedly and synergistically increases incidence of severe Bleomycin lung toxicity
- Rapid Intravenous Bleomycin Infusion: may be a risk factors (slower infusion rates and IM injection have been suggested to address this issue)
- Renal Failure (see Chronic Kidney Disease, [[Chronic Kidney Disease]]): 80% of Bleomycin is eliminated renally
Classic Bleomycin Pneumonitis
- Epidemiology: most common pattern
- Diagnosis
- Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]]): restrictive pattern
- DLCO
- Detection of Decreased DLCO on Pre-Bleomycin Screening: predicts the subsequent development of clinical pulmonary disease
- Progressive Decrease in DLCO During Bleomycin Treatment: further bleomycin administration should stopped
- VC and Pulmonary Capillary Blood Flow: may be better predictors of lung toxicity
- CXR/Chest CT
- Alveolar or interstitial pattern with lower-lobe predominance
- Primarily subpleural location
- Chest CT Scan Has Better Sensitivity Than CXR: CXR is positive in only 15% of cases, while CT is positive in 38% of cases
- Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]]): useful to exclude infection
- Bronchoalveolar Lavage: polymophonuclear or lymphocyte or eosinophil predominance
- Lung Biopsy
- Diffuse alveolar damage: non-specific
- End-stage bleomycin-induced fibrosis resembles usual interstitial pneumonitis (see Usual Interstitial Pneumonia, [[Usual Interstitial Pneumonia]])
- Clinical
- Treatment
- Withdraw Drug Permanently: if progressive decrease in DLCO
- Corticosteroids (see Corticosteroids, [[Corticosteroids]]): indicated
- Prognosis
- Mild-Moderate Pulmonary Toxicity: if patient survives the acute event, pulmonary function test and radiographic changes are fully reversible within 6 mo-2 yrs
- Moderate-Severe Pulmonary Toxicity (with Severe Hypoxemia Due to Pulmonary Fibrosis): usually progresses despite corticosteroids
- Mortality Rate: up to 3% of bleomycin-treated patients die from pulmonary toxicity
Bleomycin-Induced Pulmonary Infiltrates with Eosinophilia-Type Pattern (see Drug-Induced Pulmonary Eosinophilia, [[Drug-Induced Pulmonary Eosinophilia]])
- Epidemiology: less common pattern
- Physiology: hypersensitivity reaction
- Diagnosis
- CXR/Chest CT: alveolar or interstitial pattern with lower-lobe predominance
- Bronchoscopy (see Bronchoscopy, [[Bronchoscopy]])
- Bronchoalveolar Lavage: eosinophilia
- Clinical
- Fever (see Fever, [[Fever]]): acute onset
- Bronchoalveolar Lavage Fluid Eosinophilia (see Bronchoscopy, [[Bronchoscopy]])
- Peripheral Eosinophilia (see Peripheral Eosinophilia, [[Peripheral Eosinophilia]])
- Treatment
- Withdraw Drug + Corticosteroids (see Corticosteroids, [[Corticosteroids]]): usually rapidly responsive to corticosteroids
Bleomycin-Induced “Radiation Recall” Phenomenon (see Radiation Therapy, [[Radiation Therapy]])
- Epidemiology: bleomycin may reactivate prior radiation-induced lung disease
Bleomycin-Induced Lung Nodules (Cryptogenic Organizing Pneumonia-Type Pattern) (see Cryptogenic Organizing Pneumonia, [[Cryptogenic Organizing Pneumonia]] and Lung Nodule or Mass, [[Lung Nodule or Mass]])
- Epidemiology
- Rare pattern
- First reported in Cancer, 1989
- Seen mostly in the setting of lymphoma and seminoma
- Diagnosis
- CXR/Chest CT: lung nodules
- Lung Biopsy: cryptogenic organizing pneumonia
- Clinical: nodular pattern mimics tumor metastases (may require surgical biopsy to differentiate these lesions from metastases
Acute Chest Pain During Bleomycin Infusion (see Chest Pain, [[Chest Pain]])
- Epidemiology: occurs in 3% of cases
- Physiology: due to pleuropericarditis
Pneumothorax (see Pneumothorax, [[Pneumothorax]])
- Epidemiology: case reports
Pneumomediastinum (see Pneumomediastinum, [[Pneumomediastinum]])
- Epidemiology: case reports
Pulmonary Veno-Occlusive Disease (see Pulmonary Veno-Occlusive Disease, [[Pulmonary Veno-Occlusive Disease]])
- Epidemiology: case reports
Rheumatologic Adverse Effects
Scleroderma-Like Syndrome (see Scleroderma, [[Scleroderma]])
- Epidemiology: case reports
Other Adverse Effects
- Fever (see Fever, [[Fever]])
References
- Pulmonary veno-occlusive disease due to bleomycin therapy for lymphoma. Case reports. S Afr Med J. 1983 Oct 8;64(16):636-8
- Pulmonary veno-occlusive disease after chemotherapy. Human Pathology, Volume 14, Issue 1, January 1983, Pages 88-91