Pulmonary toxicity
Cytarabine
An antimetabolite chemotherapy utilized for a number of indications including AML, ALL and as part of conditioning regimens prior to stem cell transplantation. Pulmonary toxicity occurs as an adverse event of cytarabine therapy in 12-20% of treated patients. Patients have presented with pulmonary infiltrates and pulmonary edema requiring drug discontinuation approximately 1-2 weeks after treatment. In a review of 72 cases of cytarabine pulmonary toxicity, many occurred in relapsed leukemia patients, indicating an association between prior chemotherapy treatment and development of cytarabine pulmonary toxicity.
Patients present with mild fever, dyspnoea, cough, hypoxia and crackles on physical exam. Treatment is drug discontinuation, supportive care and possibly corticosteroids, although to date the data to support corticosteroids remains sparse. Re-challenge is not recommended, as reoccurrence of symptoms is likely.
Pulmonary toxicity
Dasatinib
A BCR-ABL tyrosine kinase inhibitor chemotherapy agent administered for CML and ALL. Severe fluid retention, which includes pulmonary edema and pleural effusions, can occur during dasatinib treatment in up to 10-23% of patients. Other lung changes can occur, such as parenchymal lung changes, ground-glass or alveolar lung opacities, or septal thickening. The time on onset of these lung changes or pleural effusions is wide-ranging, from 1 month to 500 days.
Permanent drug discontinuation is not typically required, as diuresis or thoracentesis can provide adequate treatment for the majority of pleural effusions. Instead, dasatinib may be reintroduced at a lower dosage (40 mg twice daily), often without recurrence of severe pulmonary side effects. Corticosteroids have been utilized in a small number of case reports of pulmonary changes (not pleural effusions) at doses of 40-60 mg/day of methylprednisolone with potentially positive results.
Imatinib
A BCR-ABL tyrosine kinase inhibitor chemotherapy agent used for CML, ALL and gastrointestinal stromal tumors (GIST). Fluid retention and edema can occur with imatinib treatment, including pulmonary edema, pericardial and pleural effusions. Severe fluid retention (defined as: pulmonary edema, pericardial/pleural effusion and ascites) occurred in 1.3% of newly diagnosed CML patients receiving imatinib. This increases to 2-6% with other CML patients receiving imatinib and 9-13.1% in patients with GIST.
There are cases of ILD with imatinib therapy, the largest being a case series of 27 patients. The average time to onset is 1.5 months and drug discontinuation is typically required. Symptom presentation is non-specific findings of drug cough, potentially fever, and dyspnea on exertion. Treatment is supportive care and corticosteroid treatment is usually also required for complete symptom resolution.
Leave a Reply