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
Danish Study of Bleomycin Lung Toxicity in Patients with Germ Cell Cancer (J Clin Oncol, 2016) [MEDLINE]
After 5 Years of Follow-Up, 15 of 565 Patients Died of Progressive Disease or Toxicity (Including One Patient from Bleomycin-Induced Pneumonitis)
Risk Factors for Pulmonary Function Abnormalities Following Bleomycin Treatment Included Lung Surgery, Pulmonary Embolism, Tobacco Use, and International Germ Cell Cancer Collaborative Group (IGCCCG) Prognostic Group
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): increases risk of bleomycin lung toxicity
Concomitant Granulocyte Colony Stimulating Factor (GSCF) Administration (see 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 (see 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)
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
