Carplatin

Carplatin is indicated for:

• Cancer

The side effect rates given here come from pooled data on a large group of patients who had different pretreatment prognostic features. Haematologic toxicity Bone marrow suppression is the dose-limiting toxicity of Carboplatin. At the maximum tolerated doses, given as a single agent, thrombocytopenia with platelet counts below 50,000/mm3 occurs in 25% of patients. The nadir usually comes between days 14 and 21, and recovery happens within 35 days of starting therapy. Neutropenia with granulocyte counts below 1,000/mm3 occurs in 18% of patients. Leucopenia, with nadir WBC counts below 2000/mm3, occurs in 14%, but recovery from the nadir (day 14 to 28) can be slower and usually takes place within 42 days of starting therapy. Anaemia with haemoglobin below 11 g/dL has been seen in 71% of patients. Myelosuppression may be more severe and last longer in patients with impaired kidney function, extensive prior treatment, poor performance status and age above 65. It is also worse when Carboplatin is combined with other compounds that are toxic to the bone marrow. Used as a single agent at the recommended doses and frequencies, myelosuppression is usually reversible and not cumulative. Infectious complications have been reported in 4% of patients and haemorrhagic complications in 5%. Nephrotoxicity At usual doses, abnormal kidney function has been uncommon, even though Carboplatin has been given without high-volume fluid hydration or forced diuresis. Serum creatinine rises in 6% of patients, blood urea nitrogen in 14% and uric acid in 5%. These rises are usually mild and reverse in about half of the patients. Creatinine clearance has proven to be the most sensitive measure of kidney function in patients on Carboplatin. Twenty-seven percent of patients with a baseline value of 60 mL/min or greater have a fall in creatinine clearance during therapy. Serum sodium, potassium, calcium and magnesium fall in 29%, 20%, 22% and 29% of patients respectively. Early hypotension has been reported spontaneously, and it was generally reversed by sodium replacement or free water restriction. Gastrointestinal toxicity Nausea without vomiting occurs in about 15% of patients, and vomiting in 65%. One-third of those who vomit have severe emesis. Nausea and vomiting usually go away within 24 hours of treatment, and they usually respond to antiemetic medicine (which may also prevent them). Other gastrointestinal effects are pain (17%), diarrhoea (6%) and constipation (6%). Anorexia has been reported from post-marketing surveillance. Allergic reactions Reactions to Carboplatin are infrequent, reported in less than 2% of patients. They resemble those seen with other platinum-containing compounds: erythematous rash, fever with no other apparent cause, pruritus, urticaria, and rarely bronchospasm and hypotension. Hepatic toxicity In patients with normal baseline values, abnormal liver function tests were reported as follows: total bilirubin 5%, SGOT 15% and alkaline phosphatase 24%. In pretreated ovarian cancer patients the figures were 5%, 19% and 37% respectively. These abnormalities have generally been mild and reversed in about half of the cases, although metastatic tumour in the liver may make the assessment difficult in many patients. In a limited series of patients given very high doses of Carboplatin with autologous bone marrow transplantation, severe abnormalities of liver function tests were reported. Neurotoxicity Peripheral neuropathy occurs in 4% of patients treated with Carboplatin. In most of them it is limited to paresthesias and decreased deep tendon reflexes. This effect is more frequent and more intense in patients previously treated with cisplatin. Paresthesias already present before Carboplatin starts, particularly when linked to earlier cisplatin treatment, may persist or get worse during treatment. Central nervous system symptoms have been reported in 5% of patients and often seem to be related to the use of antiemetics. Neurologic side effects overall seem to be more frequent in patients getting Carboplatin in combination, which may also be related to longer cumulative exposure.