Gastrointestinal Disorders: Severe nausea and vomiting usually begin 1-4 hours after treatment and may persist for up to a week. This may necessitate stopping treatment. These side effects are only partially relieved by standard antiemetics. Reported toxicity includes gingival platinum line.
Renal and Urinary Disorders: Acute renal toxicity, which was highly frequent in the past and represented the major dose-limiting toxicity of cisplatin, has been greatly reduced by the use of 6 to 8 hour infusions as well as by concomitant intravenous hydration and forced diuresis. Cumulative toxicity, however, remains a problem and may be severe. Renal impairment, which is associated with tubular damage, may first be noted during the second week after a dose and is manifested by an increase in serum creatinine, BUN, serum uric acid and/or decrease in creatinine clearance. Renal insufficiency is generally mild to moderate and reversible at the usual doses of the drug, however, high or repeated doses can increase the severity and duration of renal impairment and may produce irreversible renal insufficiency (sometimes fatal). Renal failure has been reported following intraperitoneal instillation of the drug.
Blood and Lymphatic System Disorders: Mild bone marrow toxicity may occur with both leucopenia and thrombocytopenia. These effects are usually reversible after ceasing treatment. Cisplatin may also induce anaemia: this is not clearly dose related and is occasionally caused by haemolysis.
Immune System Disorders: Anaphylactic and anaphylactic like reactions such as flushing, facial oedema, wheezing, tachycardia, and hypotension have been reported in patients previously exposed to cisplatin. The reactions usually occur within a few minutes of cisplatin administration and may be controlled with IV adrenaline, corticosteroids and/or antihistamines.
Ear and Labyrinth Disorders: Unilateral or bilateral tinnitus and/or hearing loss in high frequencies (>4000Hz) may occur in 10% of patients and is usually reversible. The damage to the hearing system appears to be dose related and cumulative, and it is reported more frequently in very young or very old patients. Auditory function should be monitored more closely during treatment.
Nervous System Disorders: Peripheral neuropathies occur infrequently with usual doses of the drug. They are generally sensory in nature (e.g., paraesthesia of the upper and lower extremities), but can also include motor difficulties, reduced or absent reflexes and leg weakness. Autonomic neuropathy, seizures, slurred speech, loss of taste and memory loss have also been reported. These neuropathies usually appear after prolonged therapy, but have also developed after a single drug dose. Areflexia and loss of proprioception and vibratory sensation may be seen, especially if cisplatin is given at higher doses or more frequently than recommended. In some patients they may be irreversible however, they have been partially or completely reversible in others following discontinuance of cisplatin therapy. Cerebrovascular accident has been reported in patients treated with cisplatin.
Eye Disorders: Retinal toxicity manifests as blurred vision and altered colour perception. Optic neuritis, papilloedema and cortical blindness have been reported rarely following the administration of cisplatin. These events are usually reversible after drug withdrawal.
Cardiac Disorders: Cardiovascular abnormalities (coronary disease, congestive heart failure, arrhythmias, postural hypotension, thrombotic microangiopathy etc).
Vascular Disorders: Venous thromboembolism: A significant increase in the risk of venous thromboembolic events has been reported in patients with advanced solid tumours and treated with cisplatin compared with non-cisplatin-based chemotherapy.
Vascular toxicity coincident with the use of cisplatin in combination with other antineoplastic agents have been reported rarely. The events are clinically heterogeneous and may include myocardial infarction, cerebrovascular accident (haemorrhagic and ischaemic stroke), thrombotic microangiopathy (haemolytic uremic syndrome) or cerebral arteritis. Various mechanisms have been proposed for these vascular complications.
Respiratory, Thoracic and Mediastinal Disorders: Pulmonary toxicity has been reported in patients treated with cisplatin in combination with bleomycin or 5-fluorouracil.
Hepatobiliary Disorders: Mild and transient elevations of serum AST and ALT levels may occur infrequently.
Skin and Subcutaneous Tissue Disorders: Mild alopecia. Rarely, urticarial or maculopapular skin rashes have also been observed.
Musculoskeletal and Connective Tissue Disorders: Myalgia.
Reproductive System and Breast Disorders: Cisplatin can affect male fertility. Impairment of spermatogenesis and azoospermia have been reported. Although the impairment of spermatogenesis can be reversible, males undergoing cisplatin treatment should be warned about the possible adverse effects on male fertility.
Metabolism and Nutrition Disorders: Cisplatin may also cause serious electrolyte disturbances, mainly represented by hypomagnesaemia, hypocalcaemia, and hypokalaemia, and associated with renal tubular dysfunction. Hypomagnesaemia and/or hypocalcaemia may become symptomatic, with muscle irritability or cramps, clonus, tremor, carpopedal spasm and/or tetany. Other reported toxicities are hyperuricaemia, hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH). Allopurinol may be administered to reduce serum uric acid levels.
General Disorders and Administration Site Conditions: Pyrexia, local effects such as phlebitis, cellulitis and skin necrosis (following extravasation of the drug) may also occur.