Cisplatin should be administered only under constant supervision by physicians experienced in therapy with cytotoxic agents and only when potential benefits of cisplatin therapy outweigh the possible risks. Appropriate facilities should be available for adequate management of complications should they arise.
To minimise the risk of nephrotoxicity, hydrate before, during and after therapy (see Dosage & Administration). Prior to initial therapy, then before subsequent doses, the following parameters should be monitored: renal function including Glomerular Filtration Rate (GFR), Blood Urea Nitrogen (BUN), serum creatinine and creatinine clearance; electrolytes to detect hypomagnesaemia or hypocalcaemia; auditory function; red blood cells, white blood cells and platelets; liver function and neurological status.
Nephrotoxicity: Cumulative and dose-related renal insufficiency is the major dose-limiting toxicity of cisplatin. The most commonly observed changes are a fall in GFR reflected by a rise in serum creatinine and a reduction in effective renal plasma flow.
Pre- and post-treatment hydration may reduce nephrotoxicity (see Dosage & Administration).
Renal function must return to normal before further doses are given.
Myelosuppression: Haematological toxicity is dose-related and cumulative. The lowest levels of circulating platelets and leucocytes generally occur between 18-23 days (range 7.3-45) with most patients recovering after 39 days (range 13-62). Leucopenia and thrombocytopenia are more pronounced at doses greater than 50 mg/m2.
Subsequent courses of cisplatin should not be instituted until platelets are present at levels greater than 100,000/mm3 and white cells greater than 4,000/mm3.
Anaemia: Anaemia (decrease of greater than 2 g% haemoglobin) occurs in a significant number of patients, usually after several courses of treatment. Transfusions of packed red cells may be necessary in severe cases.
A Coombs' positive haemolytic anaemia has been reported with cisplatin. Further courses with cisplatin in sensitised individuals may cause increased haemolysis.
Nausea and Vomiting: Marked nausea and vomiting occur in almost all patients treated with cisplatin and are occasionally so severe that dosage reduction or discontinuance of treatment is necessary.
Ototoxicity: Ototoxicity is cumulative and occurs mainly with high dose regimes. Tinnitus or occasional decreased ability to hear normal conversation are indications of ototoxicity, which have been frequently observed. Tinnitus is usually transient lasting from a few hours to a week after cessation of therapy. Hearing loss is usually unilateral or bilateral and occurs in the 4000 to 8000 Hz range. Frequency and severity of these hearing disorders increases with repeated doses and severe impairment may not be reversible. Auditory function should be monitored to avoid these symptoms of ototoxicity.
Hypomagnesaemia and Hypocalcaemia: Hypomagnesaemia occurs frequently and is probably due to renal tubular damage leading to wasting of magnesium ions. Secondary hypocalcaemia may occur with resulting tetany. Monitoring of electrolytes is necessary.
Neurotoxicity: Peripheral neuropathy, postural hypotension, myasthenic syndromes, seizures and visual loss may occur especially after prolonged cisplatin treatment. Cessation of cisplatin is recommended if these symptoms occur.
Anaphylaxis: Occasionally reactions secondary to cisplatin therapy have been reported. Patients receiving cisplatin should be observed carefully for possible anaphylactic like reactions and the necessary equipment and medication should be readily available to treat such reactions. Patients with a family history of atopy are at particular risk.
Cardiovascular Toxicity: Cisplatin has been found to be associated with cardiovascular toxicity (see Adverse Reactions). Patients may experience clinically heterogeneous venous thromboembolic events, myocardial infarction, cerebrovascular accidents, thrombotic microangiopathy and cerebral arteritis. Cases of pulmonary embolism (including fatalities) have been reported (see Adverse Reactions).
Use in Pregnancy: Category D: Cisplatin has been shown to be mutagenic in bacterial cultures and produces chromosome aberrations in animal cells in tissue culture. In mice cisplatin is teratogenic and embryotoxic, and its use in pregnant women is not recommended. Women of childbearing potential should use adequate contraception and cisplatin should only be used if the potential benefits outweigh the risk of therapy.
If the patient becomes pregnant whilst receiving the drug she should be advised of the hazard to the fetus.
Use in Lactation: It is not known whether cisplatin is excreted in breast milk. However, because of the potential risk to the newborn it is recommended that breastfeeding be discontinued during therapy with cisplatin in lactating women.