Cyclophosphamide pulmonary toxicity

Cyclophosphamide Cytoxan, Neosar Acute and chronic lymphocytic leukemia acute and chronic myelocytic leukemia carcinoma of ovary, breast Hodgkin disease non-Hodgkin lymphomas multiple myeloma Blood disorders (anemia, leukopenia, thrombocytopenia] Gl distress (nausea, vomiting, loss of appetite] bladder irritation hair loss car-diotoxicity pulmonary toxicity... 

Adverse Effects. Cyclophosphamide is used very cautiously as an immunosuppressant because of the possibility of severe side effects, including carcinogenic effects during long-term use. Other side effects include hematologic disorders (leukopenia, thrombocytopenia), cardiotoxicity, nephrotoxicity, and pulmonary toxicity. 

Kharasch VS, Lipsitz S, Santis W, Hallowell JA, Goorin A. Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors. Med Pediatr Oncol 1996 27(2) 85-91. 

Toxicity Gastrointestinal distress, myelosuppression, and alopecia are expected adverse effects. Hemorrhagic cystitis due to the formation of acrolein may be decreased by vigorous hydration and by use of mercaptoethanesulfonate (mesna). Cyclophosphamide may also cause cardiac dysfunction, pulmonary toxicity, and a syndrome of inappropriate ADH secretion. 

Note also that there is some evidence that colony-stimulating factors may potentiate the pulmonary toxicity of bleomycin , (p.618) and cyclophosphamide , (p.625). 

These interaetions are not firmly established, but good pulmonary function monitoring appears to be advisable when colony-stimulating factors are used with antineoplastics causing pulmonary toxicity, such as bleomycin. If interstitial pneumonia occurs, the drugs should be discontinued and high-dose corticosteroids started immediately. More study is needed. Consider also Cyclophosphamide + Colony-shmulating factors , p.625. 

Early-onset pulmonary toxicity occurred in one patient taking amiodarone after high-dose cyclophosphamide was given. Fatal pulmonary toxicity occurred in another patient taking amiodarone after a single dose of cyclophosphamide. 

Pulmonary toxicity may occur in about 10% of patients given amiodarone. Pulmonary toxicity due to cyclophosphamide may occur between 1 to 6 months after exposure or occttr as a more insidiotts form after about 6 months. The early onset of symptorrrs in the patients described above suggests accelerated mechanisms of ptrlmonary toxicity. Both cyclophosphamide and amiodarone pulmonary toxicity appear to be erthanced by oxygen and the combination of cyclophosphamide with amiodarone may enhance oxidative stress and therefore ptrlmonary toxicity. 

Although information seems to be limited to the two case reports cited, the potential for both cyclophosphamide and amiodarone to cause pulmonary toxicity is established. Be alert to the possibility of enhanced pulmonary toxicity if these drugs are given together. 

A toxicity that is unique to cyclophosphamide and ifosfamide is cystitis. Dysuria and decreased urinary frequency are the most common symptoms. Rarely, fibrosis and a permanently decreased bladder capacity may ensue. The risk of development of carcinoma of the bladder also is increased. Large intravenous doses have resulted in impairment of renal water excretion, hyponatremia, and increased urine osmolarity and have been associated with hemorrhagic subendocardial necrosis, arrhythmias, and congestive heart failure. Interstitial pulmonary fibrosis may also result from chronic treatment. Other effects of chronic drug treatment include infertility, amenorrhea, and possible mutagenesis and carcinogenesis. 

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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