Myelosuppression is the dose-limiting toxicity of carboplatin. It is generally reversible and is not cumulative when carboplatin is used as single agent and at the recommended frequencies of administration.
Adverse effects which have been observed in studies to date can be grouped under the following organ systems: Blood and lymphatic system disorders:
Leucopenia (55%), thrombocytopenia (32%), anaemia (59%). Myelosuppression is dose-related, and appears to be most common and more severe in patients who have received prior antineoplastic therapy (especially cisplatin), those who have received or who are currently receiving other myelosuppressive drugs or radiation therapy, and those with renal impairment. Transfusional support has been required in about one-fifth of patients.
Haemolytic anaemia (sometimes fatal) has also been reported.
Clinical sequelae of bone marrow/haematologic toxicity such as fever, infections, sepsis/septic shock and haemorrhage may be expected.
Haemolytic uraemic syndrome has been reported.
Nausea and vomiting (53%), nausea only (25%), diarrhoea (6%), constipation (3%). Nausea and vomiting generally are delayed 6 to 12 hours after administration of carboplatin and disappear within 24 hours, but may persist for up to 3 days in some patients. Vomiting may be delayed for 24 hours or longer after treatment in some patients. Nausea and vomiting are readily controlled (or may be prevented) with antiemetic medication. Gastrointestinal pain, mucositis and stomatitis have also been reported.
Renal and urinary disorders:
Decrease in creatinine clearance (25%); increases in uric acid (25%), blood urea nitrogen (16%) and serum creatinine (7%). Acute renal failure has been reported rarely. Risk of carboplatin-induced nephrotoxicity (e.g., impaired creatinine clearance) becomes more prominent at relatively high dosages or in patients previously treated with cisplatin.
Decreases in serum magnesium (37%), potassium (16%) and, rarely, calcium (5%). Carboplatin may also cause decreases in serum sodium levels. These changes have not been severe enough to cause clinical symptoms.
Nervous system disorders:
Peripheral neuropathy (6%) which was mild, and dysgeusia (<1%). In the majority of patients, neurotoxicity manifests mainly as paraesthesias and decreased deep tendon reflexes. The effect, more common in patients over 65 years of age, appears to be cumulative, occurring mainly in patients receiving prolonged therapy and/or in those who have received prior cisplatin therapy. Central neurotoxicity has also been reported, although this may be related to concomitant antiemetic therapy. Fatigue has been reported in patients receiving carboplatin concomitantly with paclitaxel.
Ear and labyrinth disorders:
Subclinical decrease in hearing acuity as determined by audiogram, in the high frequency (4,000 to 8,000 Hz) range (15%); clinical ototoxicity, usually manifested as tinnitus (1%). Pre-existing hearing impairment may persist or worsen with carboplatin therapy. In patients who developed hearing loss as a result of cisplatin therapy, the impairment may persist or worsen.
Increases in liver enzymes have been transient in the majority of cases. Alkaline phosphatase (ALP) (30%), aspartate aminotransferase (AST) (15%), bilirubin (4%). Substantial abnormalities in liver function test have been reported in patients treated with carboplatin at high doses and autologous bone marrow transplantation.
Immune system disorders:
In less than 2% of patients, reactions similar to those seen after cisplatin have been observed. Erythematous rash, fever, perioral tingling, urticaria, pruritus, bronchospasm, hypotension, hypoxia and pyrexia have been observed. Anaphylaxis and anaphylactoid reactions have also occurred, while exfoliative dermatitis has been reported rarely. In a few cases, no cross-reactivity was present. The frequency of allergic reactions is higher in patients who receive carboplatin in conjunction with other antineoplastic agents. Hypersensitivity reactions may occur within a few minutes after IV administration of carboplatin.
Visual abnormalities, such as transient sight loss (which can be complete for light and colours) or other disturbances may occur in patients treated with carboplatin. Improvement and/or total recovery of vision usually occurs within weeks after the drug is discontinued. Cortical blindness has been reported in patients with impaired renal function receiving high-dose carboplatin.
Neoplasms - benign, malignant and unspecified:
There have been rare reports of acute myelogenous leukaemias and myelodysplastic syndromes arising in patients who have been treated with carboplatin, mostly when given in combination with other potentially leukaemogenic agents.
Cardiac failure, ischaemic coronary artery disorders (e.g. myocardial infarction, cardiac arrest, angina, myocardial ischaemia), Kounis syndrome (vasospastic allergic angina).
Skin and subcutaneous tissue disorders:
Exfoliative dermatitis may rarely occur. Erythematous rash, pruritus, urticaria and alopecia have also been reported in association with carboplatin.
Musculoskeletal and connective tissue disorders:
Myalgias/arthralgias. This can commonly occur in patients receiving carboplatin together with paclitaxel (see Interactions).
Metabolism and nutrition disorders:
Electrolyte abnormalities (hypokalaemia, hypocalcaemia, hyponatraemia and/or hypomagnesaemia).
Alopecia (2%), flu-like syndrome (1%), reaction at injection site (<1%). Taste abnormalities, and adverse respiratory and genitourinary effects have also been reported. Pain, most likely related to tumour size, and asthenia occur frequently in patients receiving carboplatin in conjunction with cyclophosphamide.