Carmustine pulmonary toxicity

Carmustine pulmonary toxicity is well documented. Eight patients developed interstitial pulmonary fibrosis 12-17 years after exposure to carmustine in a total dose of carmustine of 770-1410 mg/m (7). 

An important synergistic reaction between radiation-related pulmonary fibrosis and tamoxifen has been described in 196 women followed for a minimum of 5 years, with a relative risk of 2.0 (39). However, others have shown that tamoxifen did not increase the pulmonary toxicity of agents such as carmustine and dacarbazine (40). 

Carmustine BCNU, BiCNU Primary brain tumors Hodgkin disease non-Hodgkin lymphomas multiple myeloma Blood disorders (thrombocytopenia, leukopenia] Gl distress (nausea, vomiting] hepatotoxicity pulmonary toxicity... 

Both carmustine and lomustine can induce thrombocytopenia and leukopenia, leading to hemorrhage and massive infection. Acute (as well as potentially fatal delayed) pulmonary toxicity also is a risk. Pulmonary toxicity is dose-related, and individuals who received the drug in childhood or early adolescence are at higher risk for the delayed reaction. The grand mal seizures that are possible from the wafer formulation of carmustine appear to result from the wafer rather than from the nitrosourea. 

Figure 1 Chest radiograph in a male with carmustine-induced pulmonary toxicity. Note the predominant upper lobe distribution of the pulmonary infiltrates typical of nitrosourea...

Weinstein AS, Diener-West M, Nelson DF, et al. Pulmonary toxicity of carmustine in patients treated for malignant ghoma. Cancer Treat Rep 1986 70 943-946. 

The main drugs in this group are lomustine, carmustine, semustine and streptozotocin. The nitrosoureas are lipophilic and cross the blood-brain barrier. They are therefore effective against brain tumours. They cause a severe cumulative bone marrow depression that starts within 1-2 months of treatment. Lomustine and carmustine cause direct injury to the pulmonary epithelium leading to alveolar fibrosis. Streptozotocin has little bone marrow toxicity, but destroys the pancreatic 3 cells, causing diabetes mellitus. 

A clinical study that was started to find out if pentostatin would improve the immunosuppressive effects of cyclophosphamide, carmustine and etoposide in bone marrow transplant patients was stopped when acute and fatal cardiovascular collapse developed in the first 2 patients. Both patients had been given cyclophosphamide 800mg/m and etoposide 200 mg/m, both every 12 hours for 8 doses, and carmustine 112 mg/m daily for 4 doses. On day 3 pentostatin 4 mg/m, given over 4 hours, was added. Within 8 to 18 hours after completion of chemotherapy both patients developed confusion, hypothermia, hypotension, respiratory distress, pulmonary oedema, and eventually fatal ventricular fibrillation within 45 to 120 minutes of the first symptoms. A later study in rats similarly found that pentostatin markedly increased the acute toxicity of cyclophosphamide. The reasons for this cardiotoxicity are not understood. Neither of the 2 patients had previously shown any evidence of cardiac abnormalities. ... 

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