Heart failure cyclophosphamide

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. 

Of 80 patients who received cyclophosphamide 50 mg/ kg/day for 4 days in preparation for bone marrow grafting 17% had symptoms consistent with cyclophosphamide cardiotoxicity (6). Six died from congestive heart failure. Older patients were at greatest risk of developing cardiotoxicity. 

In six patients who developed heart failure after high-dose conditioning therapy before stem cell transplantation, cyclophosphamide was suspected, despite the possible involvement of four drugs (7). The authors suggested monitoring high-risk patients. 

Corrected QT dispersion was a predictor of acute heart failure after high-dose cyclophosphamide chemotherapy (5.6 g/m over 4 days) in 19 patients (8). 

The most common cause of hyponatremia in hospital patients is SIADH. However, other disorders can cause dilutional hyponatremia and must be differentiated from SIADH. These conditions include (1) congestive heart failure, (2) renal insufficiency, (3) nephrotic syndrome, (4) liver cirrhosis, and (5) hypothyroidism. Excessive administration of hypotonic fluids and treatment with drugs that stimulate AVP (e.g., chlorpropamide, vincristine, clofibrate, carbamazepine, nicotine, phenothiazines, and cyclophosphamide) can cause dilutional hyponatremia as well. Hyponatremia may also occur from renal or extrarenal sodium losses (depietional hyponatremia) as a result of vomiting, diarrhea, excessive sweating, diuretic abuse, saltlosing nephropathy, or mineralocorticoid deficiency. 

D. Monoclonal Antibodies Rituximab is a monoclonal antibody to a surface protein in non-Hodgkin s lymphoma cells. It is presently used with conventional anticancer drugs (eg, cyclophosphamide plus vincristine plus prednisone) in low grade lymphomas. Trastuzumab is a monoclonal antibody to a surface protein in breast cancers that overexpress the HER2 protein. Acute toxicity of these antibodies includes nausea and vomiting, chills, fevers, and headache. Rituximab use is associated with hypersensitivity reactions and myelosuppression. Trastuzumab may cause cardiac dysfunction, including congestive heart failure. 

---