What are the contraindications for bleomycin, including hypersensitivity, pre‑existing pulmonary fibrosis or interstitial lung disease, severe chronic lung disease (e.g., severe COPD), impaired renal function (creatinine clearance <30 mL/min), pregnancy, breastfeeding, and cumulative dose limits (>400‑450 units or >300 units in patients >70 years)?

Bleomycin Contraindications

There are no absolute contraindications to bleomycin, but extreme caution is required in patients over 40 years of age, those with impaired renal function (GFR <80 ml/min), significant smoking history, and pre-existing lung disease—particularly pulmonary fibrosis. 1

Relative Contraindications Requiring Heightened Caution

Age-Related Risk

• Patients over 40 years have a twofold increased risk of bleomycin-induced pulmonary toxicity and should not receive bleomycin if safer alternatives exist. 1
• Those over 30 years demonstrate 4.8% higher grade ≥1 toxicity compared to younger patients. 1
• Baseline CT thorax is mandatory for all patients over 40 before initiating bleomycin therapy. 1

Renal Impairment

• GFR <80 ml/min increases the hazard ratio for bleomycin pulmonary toxicity by 3.3-fold and represents a major risk factor. 2
• Since bleomycin is 70% renally excreted, reduced renal function prolongs drug half-life and increases toxicity risk. 1
• Fatal pulmonary toxicity has been reported with cumulative doses as low as 60 units in patients with chronic renal insufficiency. 3
• Renal function must be checked prior to every cycle of bleomycin administration. 1
• Concomitant cisplatin use further compounds renal toxicity and bleomycin accumulation risk. 1

Pre-Existing Pulmonary Disease

• Pre-existing pulmonary fibrosis or symptomatic lung pathology represents a major contraindication to bleomycin use. 1, 4
• Patients with pre-existing lung disease should only receive bleomycin after careful risk-benefit assessment by a consultant. 1
• Hypoxic patients should generally not receive bleomycin (66% of UK specialists would never use it in this population). 1

Smoking History

• Significant smoking history increases bleomycin pulmonary toxicity risk, though specific pack-year thresholds are not definitively established. 1, 4
• The majority (77%) of specialists would consider bleomycin use in smokers only after individual risk assessment. 1

Cumulative Dose Limits

• Cumulative bleomycin doses >300 units increase the hazard ratio for pulmonary toxicity by 3.5-fold. 2
• All patients receiving >300 units must undergo post-treatment CT scan. 1
• Stage IV disease at presentation increases toxicity risk (HR 2.6), particularly when combined with high cumulative doses. 2

Critical Monitoring Requirements

Baseline Assessment

• CT thorax for all patients over 40 years. 1
• Baseline pulmonary function tests (PFTs) should be considered as a reference point for future comparison, though they should not be used in isolation to predict toxicity or guide treatment decisions. 1
• Renal function assessment is mandatory before initiating therapy. 1

During Treatment Surveillance

• A toxicity checklist must be used before and after every cycle, with particular attention to new cough—the most sensitive symptom for predicting toxicity. 1, 5
• Renal function must be checked prior to every cycle. 1
• If new cough or dyspnea develops, omit the bleomycin dose immediately and obtain HRCT before any further administration. 1, 4
• Chest X-ray has extremely low sensitivity and should never be used to investigate suspected toxicity. 1, 5

High-Risk Patient Management

• Patients with multiple risk factors (age >40, GFR <80 ml/min, smoking history, pre-existing lung disease) should be considered for alternative regimens such as etoposide-cisplatin (EP) or carboplatin-etoposide. 1, 2
• Continuation of bleomycin in the face of new respiratory symptoms requires consultant-level decision-making with multidisciplinary team input including experienced radiologists. 1

Common Pitfalls to Avoid

• Never rely on PFTs alone to decide whether to initiate bleomycin therapy—they are only weakly correlated with toxicity and only at the end of treatment. 1, 4
• Never use chest X-ray to investigate suspected bleomycin toxicity—HRCT is the investigation of choice. 1, 5
• Never continue bleomycin without consultant approval when new respiratory symptoms develop—cessation may reverse lung damage while continuation can worsen toxicity. 1
• Do not assume bleomycin toxicity is purely dose-dependent—idiosyncratic severe reactions can occur at lower doses. 1
• Do not overlook infection as a potential mimic or coexisting condition with bleomycin toxicity. 1, 5