From the Guidelines
Post chemotherapy pneumonitis should be treated with corticosteroids, such as prednisone at 1 mg/kg/day for 1-2 weeks, followed by a gradual taper over 4-6 weeks, as recommended by the American College of Chest Physicians evidence-based clinical practice guidelines 1.
Treatment Approach
The treatment approach for post chemotherapy pneumonitis involves stopping the offending chemotherapy agent and initiating anti-inflammatory therapy with corticosteroids.
- Corticosteroids, such as prednisone, are recommended at a dose of 1 mg/kg/day for 1-2 weeks, followed by a gradual taper over 4-6 weeks 1.
- Macrolides can be considered as steroid-sparing agents, as mentioned in the American College of Chest Physicians evidence-based clinical practice guidelines 1.
- Supportive care includes supplemental oxygen if hypoxemia is present, and antibiotics may be necessary if infection cannot be ruled out.
Prevention Strategies
Prevention strategies for post chemotherapy pneumonitis include:
- Limiting the cumulative dose of high-risk agents, especially bleomycin 1.
- Avoiding concurrent oxygen therapy during bleomycin administration 1.
- Considering dose reductions in patients with pre-existing lung disease or renal impairment 1.
- Monitoring patients with pulmonary function tests before and during treatment with high-risk agents 1.
Clinical Presentation
The condition occurs because chemotherapy drugs can directly damage lung tissue through oxidative stress, immune-mediated inflammation, or direct cytotoxicity to pneumocytes.
- Symptoms typically include progressive dyspnea, dry cough, fatigue, and sometimes fever, usually appearing weeks to months after chemotherapy initiation 1.
- Early recognition is crucial as the condition can progress to pulmonary fibrosis if not properly managed 1.
Diagnosis and Management
The diagnosis and management of post chemotherapy pneumonitis involve a comprehensive approach, including:
- Identifying risk factors, such as patients with dysimmune risk factors or personal comorbidities 1.
- Educating the patient and their entourage on potential side effects of immunotherapy 1.
- Pursuing warning signs and eliminating the most serious illnesses that would require immediate treatment 1.
- Performing an extensive differential work-up to address the most common overlapping toxicities 1.
- Seeking expert advice and collaborating with organ specialists 1.
From the FDA Drug Label
Pneumonitis, pulmonary fibrosis, pulmonary veno-occlusive disease and other forms of pulmonary toxicity leading to respiratory failure have been reported during and following treatment with cyclophosphamide. Late onset pneumonitis (greater than 6 months after start of cyclophosphamide) appears to be associated with increased mortality Pneumonitis may develop years after treatment with cyclophosphamide. Monitor patients for signs and symptoms of pulmonary toxicity.
Post chemotherapy pneumonitis is a potential side effect of cyclophosphamide treatment.
- The condition may occur during or after treatment with cyclophosphamide.
- Late onset pneumonitis (occurring more than 6 months after starting cyclophosphamide) is associated with increased mortality.
- Patients should be monitored for signs and symptoms of pulmonary toxicity. 2
From the Research
Post Chemotherapy Pneumonitis
- Post chemotherapy pneumonitis is a complication of high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) regimens containing BCNU, with an incidence of 22% 3.
- The risk factors for pneumonitis include prior mediastinal radiation, total BCNU dose above 1000 mg, and age less than 54 3.
- Immune checkpoint inhibitors can also cause pneumonitis, with a prevalence of 4% in patients treated with these agents 4.
- Steroid-resistant/refractory pneumonitis is a serious condition with a high mortality rate of 67% at 2 months 4.
- Cyclophosphamide may be a treatment option for pneumonitis after corticosteroid failure, but further investigations are needed 4.
Pneumonitis after Chemoradiation and Durvalumab
- The cumulative grade >2 pneumonitis rate was 26.5% in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy followed by durvalumab 5.
- Pneumonitis development did not significantly impact progression-free survival or overall survival in these patients 5.
- Durvalumab re-challenge appeared feasible after pneumonitis treatment with steroids, with a recurrence rate of 14% 5.
Mechanisms of Pneumonitis and Fibrosis
- Activation of lymphocytes by immunotherapy or infiltration of inflammatory cells can induce pneumonitis 6.
- The polarization of macrophages toward M2 cells and the release of anti-inflammatory cytokines stimulate fibrosis 6.
- Other changes such as epithelial-mesenchymal transition (EMT), oxidative stress, and the upregulation of inflammatory mediators can also potentiate lung fibrosis and pneumonitis 6.