Bleomycin Chemotherapy Side Effects
Bleomycin causes pulmonary toxicity in approximately 10% of treated patients, with progression to fatal pulmonary fibrosis in 1% of cases, making lung toxicity the most critical and life-threatening side effect requiring vigilant monitoring. 1, 2
Major Side Effects by System
Pulmonary Toxicity (Most Critical)
Risk Factors:
- Age >40 years significantly increases risk (HR 2.3) 3
- Cumulative dose >300 units (HR 3.5 for toxicity) 3
- Renal dysfunction with GFR <80 ml/min (HR 3.3) 3
- Significant smoking history 4
- Pre-existing lung disease 4
- Stage IV disease at presentation (HR 2.6) 3
Clinical Presentation:
- Cough is the most sensitive early symptom and should trigger immediate investigation 4, 5
- Dyspnea develops as toxicity progresses 1, 6
- Symptoms typically appear during treatment but can manifest more than 10 years after cessation of therapy 7
- Median time to documented toxicity is 4.2 months from start of treatment 3
Mortality Impact:
- Overall mortality from bleomycin pulmonary toxicity is 4.2% of all treated patients 8
- Among patients who develop pulmonary toxicity, mortality reaches 24% 8
- Patients with pulmonary toxicity have 5-year overall survival of 63% versus 90% in unaffected patients (P=0.001) 8
Idiosyncratic Anaphylactoid Reactions
- Occur in approximately 1% of lymphoma patients 1, 2
- Consist of hypotension, mental confusion, fever, chills, and wheezing 1
- Usually occur after the first or second dose, requiring careful monitoring during initial administration 1, 2
- May be immediate or delayed for several hours 1
Dermatologic and Mucosal Toxicity
- Affect approximately 50% of treated patients 1
- Include erythema, rash, striae, vesiculation, hyperpigmentation, and skin tenderness 1
- Hyperkeratosis, nail changes, alopecia, pruritus, and stomatitis also reported 1
- Scleroderma-like skin changes can develop 1
- Typically manifest in the second and third week of treatment after 150-200 units administered 1
- Require discontinuation of therapy in 2% of patients 1
Vascular Toxicity
- Clinically heterogeneous events including myocardial infarction, cerebrovascular accident, thrombotic microangiopathy, and cerebral arteritis 1
- Raynaud's phenomenon reported, particularly when bleomycin combined with vinblastine with or without cisplatin 1
Other Systemic Effects
- Fever, chills, and vomiting 1
- Anorexia and weight loss that may persist long after medication termination 1
- Renal toxicity with deterioration in renal function tests 1, 2
- Hepatic toxicity with deterioration in liver function tests 1, 2
Special Considerations for Pre-existing Lung Disease
Bleomycin should be used with extreme caution in patients with compromised pulmonary function, as there are no absolute contraindications but pre-existing lung disease substantially increases risk. 4, 1, 2
- Patients with multiple risk factors (age >40, smoking history, renal dysfunction, pre-existing lung disease) are at highest risk 4
- These patients require enhanced monitoring with baseline HRCT and symptom surveillance 5, 9
- Consider alternative drug regimens or dose restriction in high-risk patients 3
Oxygen-Related Complications
- Bleomycin sensitizes lung tissue, creating greater risk of pulmonary toxicity when oxygen is administered during surgery 1
- Lung damage can occur at lower oxygen concentrations than usually considered safe 1
- Maintain FiO2 at approximately 25% (room air concentration) during surgery and postoperative period 1
- Focus fluid replacement on colloid rather than crystalloid administration 1