Cyclophophamide toxicity

Gastrointestinal distress, myelosuppression, and alopecia are expected adverse effects of cyclophosphamide. Hemorrhagic cystitis resulting from 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 antidiuretic hormone (ADH) secretion The most prominent toxicities of both drugs (after alopecia, nausea, vomiting, and diarrhea) are bone marrow depression, especially leukocytosis, and hemorrhagic cystitis, which can lead to fibrosis of the bladder. The latter toxicity has been attributed to acrolein in the urine in the case of cyclophosphamide and to toxic metabolites of ifosfamide. [Note: Adequate hydration as well as IV injection of MESNA (sodium 2-mercaptoethane sulfonate), which neutralizes the toxic metabolites, minimizes this problem.] Other toxicities include effects on the germ cells, resulting in amenorrhea, testicular atrophy, aspermia, and sterility. Veno-occlusive disease of the liver is seen in about 25 percent of the patients. A fairly high incidence of neurotoxicity has been reported in patients on high-dose ifosfamide, probably due to the metabolite, chloroacetaldehyde. Secondary malignancies may appear years after therapy.