The following dose-dependent side effects can occur, which in most cases are reversible.
Blood: Leucocytopenia, with the risk of life-threatening infections; thrombocytopenia, with the risk of bleeding; and anaemia, with a haemoglobin decrease of >2 g/100 mL compared to the initial value. The lowest leucocyte and thrombocyte counts normally occur 1-2 weeks after start of treatment and recover within 3-4 weeks.
A combination treatment with other myelosuppressive agents may require dose adjustments. Therefore, the doctor should refer to the relevant tables on dose adjustment of cytotoxic drugs to the blood counts at the beginning of the cycle and the nadir-adjusted dosage of cytostatic agents.
Gastrointestinal Side Effects: Frequently, nausea and vomiting; seldom anorexia, diarrhoea, constipation and stomatitis.
Haemorrhagic colitis and ulcerations on the buccal mucosa have been reported in isolated cases.
Urogenital Tract: Therapy-dependent cystitis after administration of Endoxan is a frequent side effect requiring an interruption of treatment.
After elimination into the urine, cyclophosphamide and its metabolites lead to changes in the bladder eg, bladder-wall oedema, suburothelial bleedings, interstitial inflammations with fibrosis and, eventually, to a rigidity of the bladder wall. Cystitis is initially sterile, but secondary microbial invasion may occur. In isolated cases, haemorrhagic cystitis with subsequent death has been reported. Renal lesions (in particular with a history of impaired renal function) are rare side effects after high doses.
Note: Treatment with Uromitexan (mesna), adequate hydration and alkalinisation of the urine can markedly reduce the frequency and severity of these urotoxic side effects.
In case of concomitant diuretic treatment, urinary alkalinisation is not allowed due to the risk of an increased bladder toxicity.
Hepatotoxicity: In rare cases, impaired liver function has been reported, identified by an increase of the relevant laboratory parameters (SGOT, SGPT, γ-GT, alkaline phosphatase, bilirubin).
Cardiovascular System: Secondary cardiomyopathy induced by cytotoxic drugs has particularly been reported after high doses of cyclophosphamide (120-240 mg/kg body weight). There are signs indicating an enhanced cardiotoxicity of cyclophosphamide after previous radiotherapy of the cardiac region and concomitant anthracycline treatment.
Secondary Tumours: As with cytotoxic therapy in general, treatment with cyclophosphamide involves the risk of secondary tumours and their precursors as late sequelae. The risk of developing urinary tract cancer as well as myelodysplastic alterations partly progressing to acute leukaemias is increased. Animal studies prove that the risk of bladder cancer can be markedly reduced by giving an adequate dose of Uromitexan (mesna).
Other Side Effects: Alopecia, a frequent side effect, is in general reversible. Cases of pigment changes of the palms, finger nails and the soles have also been reported. In addition, the following side effects were observed:
Partly irreversible impairment of spermatogenesis, with resulting azoospermia or persistent oligospermia. Less frequently irreversible ovulation disturbances with resulting amenorrhea.
Chronic interstitial lung fibrosis.
Syndrome of inappropriate ADH secretion (Schwarz-Bartter syndrome) with hyponatraemia and water retention.
Inflammation of the skin and mucous membrane.
Hypersensitivity reactions, in isolated cases progressing to shock.
Blurred vision and episodes of dizziness.
Note: Attention should be paid to meticulous oral hygiene. Regular blood counts are indicated during treatment: Intervals of 5-7 days at initial therapy, intervals of 2 days in case the level of white cells decreases <3000/mm3, eventually daily. Checks every 2 weeks are generally sufficient in case of long-term therapy. The urinary sediment should be checked regularly for erythrocytes.