Bone marrow suppression is the dose-limiting toxicity of carboplatin. Thrombocytopenia with platelet counts below 50,000/mm3
occurs in 25% of the patients; neutropenia with granulocyte counts below 1000/mm3
occurs in 16% of the patients; leukopenia with white blood cell counts above 2000/mm3
occurs in 15% of the patients. This usually occurs about day 21 in patients receiving single agent therapy. By day 28, 90% of the patients have platelet counts above 100,000/mm3
, 74% have neutrophil counts above 2000/mm3
; 67% have leucocyte counts above 4000/mm3
. Marrow suppression is usually more severe in patients with impaired kidney function. Patients with poor performance status have also experienced a higher incident of severe leukopenia and thrombocytopenia. Anemia with hemoglobin less than 11 g/dL occurs in majority of the patients who starts therapy with a baseline above value. The incidence of anemia increases with the increasing exposure to carboplatin. Transfusions may be required in some patients treated with carboplatin. Bone marrow depression may be more severe when carboplatin is combined with other bone marrow suppressing drugs or with radiotherapy.
Vomiting occurs in about 65% of the patients, and in one third of these patients, it is severe. Nausea alone occurs in an additional 10-15% of patients. Both nausea and vomiting usually cease within 24 hours of treatment and are often responsive to antiemetic measures. Emesis was increased when carboplatin was used in combination with other emetogenic compound. Other gastrointestinal effects observed frequently were in pain in 17% of the patients; diarrhea, in 6% and constipation, also in 6%.
Peripheral neuropathies have been observed in small numbers of patients receiving carboplatin with mild paresthesias occurring most frequently. Patients older than 65 years have an increased risk for peripheral neuropathies. Clinical ototoxicity and other sensory abnormalities such as visual disturbances and change in taste occur rarely. Central nervous systems have been reported in fewer patients and appear to be most often related to the use of antiemetics. Although the overall incidence of peripheral neurologic adverse effects induced by carboplatin is low. Prolonged treatment may result in cumulative neurotoxicity.
Development of abnormal renal function test results is uncommon with carboplatin. Creatinine clearance has proven to be the most sensitive measures of kidney functions in patients receiving carboplatin, and it appears to be most useful test for correlating drug clearance and bone marrow suppression.
Abnormal liver function tests in patients may be found with normal baseline value. These abnormalities (eg, SGOT, total bilirubin and alkaline phosphatase) have generally been mild and reversible in about half of the cases, although the role of metastatic tumor in the liver may complicate the assessment in many patients.
The abnormally decreased serum electrolyte values may be found in some patients. Electrolyte supplementation is not routinely administered concomitantly with carboplatin and these electrolyte abnormalities are rarely associated with symptoms.
Hypersensitivity to carboplatin develops only in small number of patients and consists of rash, urticaria, erythema, pruritus and rarely, bronchospasm and hypotension. These reactions are successfully managed with standard epinephrine, corticosteroid and antihistamine therapy.
Pain and asthenia occurs most frequently. Alopecia, cardiovascular, respiratory, genitourinary and mucosal adverse effects occur only in small number of patients.