Incidences of adverse reactions reported here under are based on cumulative data obtained in a large group ofpatients with various pretreatment prognastic features.Haematologic toxicity: Bone marrow suppression is the dose-limited toxicity of Carboplatin. At maximum tolerated dosages of Carboplatin administered as a single agent, thrombocytopenia, with platelet counts of less than 50,000/mm 3 , occurs in 25% of the patients. The nadir usually occurs between days 14 and 21, with recovery within 35 days from the start of therapy. Neutropenia with granulocyte counts below 1,000/mm 3 occurs in 18% of patients. Leucopenia, with nadir WBC counts of less than 2000/mm 3 , occurs in 14% of the patients but its recovery from the day of nadir (day 14-28) may be slower and usually occurs within 42 days from the start of therapy. Anaemia with haemoglobin values below 11 g/dL has been is observed in 71% of the patients. Myelosuppression may be more severe and prolonged in patients with impaired kidney function, extensive prior treatment, poor performance status and age above 65. Myelosuppression is also worsened by therapy combining Carboplatin with other compounds that are toxic to the bone marrow. Myelosuppression is usually reversive and not cumulative when Carboplatin is used as a single agent and at the recommended dosages and frequencies of administration. Infectious and haemorrhagic complications have been reported in 4% and 5% of the patients given Carboplatin, respectively.Nephrotoxicity: When given in usual doses, development of abnormal renal function has been uncommon, despite the fact that Carboplatin has been administered without high-volume fluid hydration and/or forced diuresis. Elevation of serum creatinine occurs in 6% of patients, elevation of blood urea nitrogen in 14%, and of uric acid in 5% of patients. These are usually mild and are reversible in about one-half the patients. Creatinine clearance has proven. to be the most sensitive renal function measure in patients receiving Carboplatin. Twenty-seven percent of patients who have a baseline value of 60 mL/min or greater, experience a reduction in creatinine clearance during Carboplatin therapy. Decreases in serum electrolytes sodium, potassium, calcium, magnesium occur in 29%, 20%, 22%, 29% of patients respectively. Spontaneous reports of early hypotension have been reported which were generally reversed by sodium replacements or free water restriction.Gastrointestinal toxicity: Nausea without vomiting occurs in about 15% of the patients receiving Carboplatin; vomiting has been reported in 65% of the patients. One-third of those patients who vomit suffer severe emesis. Nausea and vomiting usually disappear within 24 hours after treatment and are usually responsive to (and may be prevented by) antiemetic medication. Other gastrointestinal side effects consist of pain (17%); diarrhoea (6%), and constipation (6%). Anorexia has been reported from post-marketing surveillance.Allergic reactions: Infrequent reactions to Carboplatin have been reported in less than 2% of the patients. These reactions are similar to those observed after administration of other platinum-containing compounds, i.e. erythematous rash, fever with no other apparent cause, pruritus, urticaria, rarely bronchospasm and hypotension.Hepatic Toxicity: The incidences of abnormal liver function tests in patients with normal baseline values were reported as follows: total bilirubin, 5%; SGOT, 15%; and alkaline phosphatase, 24%; (5%, 19%, and 37%, respectively, in pretreated ovarian cancer patients). These abnormalities have generally been mild and reversible in about one-half of the cases, although the role of metastatic tumor in the liver may complicate the assessment in many patients. In a limited series of patients receiving very high dosages of carboplatin and autologous bone marrow transplantation, severe abnormalities of liver function tests were reported.Neurotoxicity: The incidence of peripheral neuropathies after treatment with Carboplatin is 4%. In the majority of the patients neurotoxicity is limited to paresthesias and decreased deep tendon reflexes. The frequency and intensity of this side effect increase in patients previously treated with cisplatin. Paresthesias present before commencing Carboplatin therapy, particularly if related prior cisplatin treatment, may persist or worsen during treatment with Carboplatin. Central nervous symptoms have been reported in 5% of patients and often appear to be related to the use of antiemectics. The overall frequency of neurologic side effects seems to be increased in patients receiving Carboplatin in combination. This may also be related to longer cumulative exposure.
