Table 1.
Best-practice guidelines for the use of bleomycin in germ cell tumours in the UK
| Stage | Recommendation | Evidence |
|---|---|---|
| Baseline investigations | Patients over the age of 40 should receive a baseline CT Thorax prior to commencing bleomycin. | 10(Level 1b) |
| Pulmonary function tests | Baseline PFTs can be a useful reference in the case of subsequent toxicity and should be considered where possible. | Expert opinion (Level 5) |
| PFTs should not be used in isolation to aid in a decision as to whether or not to treat with bleomycin. | 10(Level 1b) | |
| PFTs should not be used as a first-line investigation for suspected lung toxicity. | 10(Level 1b) | |
| PFTs may aid in the diagnosis of suspected toxicity and may guide management of toxicity. Involvement of a respiratory physician should be considered. |
28(Level 1b) Expert opinion (Level 5) |
|
| Contraindications to bleomycin | There are no absolute contraindications to use but caution should be exercised with increasing age, significant smoking history, reduced renal function and pre-existing lung disease (in particular pre-existing fibrosis or other symptomatic pathology) | Expert opinion (Level 5) |
| Administration of bleomycin | There is no evidence to support a bolus vs. continuous administration regimen. Typical administration schedules involve a weekly bleomycin bolus or short infusion. | 10(Level 1b)20 (Level 1b) |
| Development of bleomycin-related lung toxicity | Cessation of therapy may reverse lung damage and continuing bleomycin therapy may result in worsening toxicity. Continuation in the face of new symptoms should be a consultant decision. | 35(Level 1b) |
| Cough is the most sensitive symptom for prediction of toxicity. Dyspnoea is also a significant symptom. | 10(Level 1b)15 (Level 2a) | |
| All CT-confirmed diagnoses of bleomycin lung toxicity should be considered for oral Prednisolone (0.5 mg/kg) for 7 days and reduce | 32,33(Level 4) Expert opinion (Level 5) | |
| HRCT chest is indicated if toxicity is suspected with referral to a respiratory physician with an interest in interstitial lung disease. | Expert opinion (Level 5) | |
| Infection should always be considered and treated, and may mimic, coexist with and drive bleomycin-related lung toxicity | Expert opinion (Level 5) | |
| PFTs may have a role in cases of diagnostic uncertainty or high-risk groups (see text) | Expert opinion (Level 5) | |
| Post-treatment monitoring | All patients receiving more than 300 units of bleomycin should receive a post-treatment CT scan | 13(Level 2a) Expert opinion (Level 5) |
| Further investigations should be symptom-led. PFTs are only weakly correlated with increased toxicity at the end of treatment, with DLCO being most significant. | 10(Level 1b) | |
| Symptom monitoring | A ‘toxicity checklist’ should be used before and after every cycle of bleomycin. An example of this can be found in supplementary information 2. | Expert opinion (Level 5) |
| Renal function should be checked prior to every cycle of treatment. | Expert opinion (Level 5) | |
| Cough is the most important symptom and development of a new cough should trigger further investigation (with HRCT in the first instance). |
10(Level 1b) Expert opinion (Level 5) |
|
| Advice sheet | Every patient receiving bleomycin should receive a post-treatment advice sheet. An example of this can be found in supplementary information 3. | Expert opinion (Level 5) |
Levels of evidence are based on the Centre for Evidence-based Medicine Levels of Evidence. http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/