Bone marrow suppression is the dose-limiting toxicity of carboplatin. Thrombocytopenia with platelet counts below 50,000/mm3
occurs in 35% of pretreated ovarian cancer patients. The nadir usually occurs between 14-21 days, with recovery within 35 days from the start of therapy.
Leucopenia has also occurred in approximately 20% of patients but its recovery from the day of nadir (14-28 days) may be slower and usually occurs within 42 days from the start of therapy. A hemoglobin decrease may be observed in some patients.
Myelosuppression may be more severe and prolonged in patients with impaired renal function, extensive prior treatment, poor performance status and age above 65.
Myelosuppression is also worsened by therapy combining carboplatin with other compounds that are myelosuppressive.
Myelosuppression is usually reversible and not cumulative when carboplatin is used as a single agent and at the recommended dosage and frequencies of administration.
Infections as complications have occasionally been reported. Hemorrhagic complications, usually minor, have also been reported.
Renal toxicity is usually not dose-limiting in patients receiving carboplatin, nor does it require preventive measures such as high volume fluid hydration or forced diuresis. Nevertheless, increasing blood urea or serum creatinine levels can occur. Renal function impairment, as defined by a decrease in the creatinine clearance below 60 mol/min, may also be observed. The incidence and severity of nephrotoxicity may increase in patients who have impaired kidney function before carboplatin treatment. It is not clear whether an appropriate hydration program might overcome such an effect, but dosage reduction or discontinuation of therapy is required in the presence of severe alteration of renal function tests.
Decreases in serum electrolytes (magnesium, potassium and rarely, calcium) have been reported after treatment with carboplatin but have not been reported to be severe enough to cause the appearance of clinical signs or symptoms.
Nausea without vomiting occurs in about ¼ of the patients receiving carboplatin; vomiting has been reported in half of the patients and 1/3 of these suffer severe emesis. Nausea and vomiting usually disappear within 24 hours after treatment and are usually responsive to (and may be prevented by) anti-emetic medication. ¼ of patients experience no nausea or vomiting.
Hypersensitivity to carboplatin has been reported in 2% of the patients. These allergic reactions have been similar in nature and severity to those reported with other platinum-containing compounds, i.e., rash, urticaria, erythema, pruritus, and rarely, bronchospasm and hypotension.
Subclinical decrease in hearing acuity, consisting of high-frequency (4000-8000 Hz) hearing loss determined by audiogram, has been reported in 15% of the patients treated with carboplatin. However, only 1% of patients present with clinical symptoms, manifested in the majority of cases by tinnitus. In patients who have been previously treated with cisplatin and have developed hearing loss related to such treatment, the hearing impairment may persist, or worsen.
The incidence of peripheral neuropathies after treatment with carboplatin is 6%. In the majority of the patients neurotoxicity is limited to paraesthesia and decreased deep tendon reflexes. The frequency and intensity of this side effect increases in patients previously treated with cisplatin.
Abnormalities of liver function tests (usually mild to moderate) have been reported with carboplatin in about 1/3 of the patients with normal baseline values. The alkaline phosphatase level is increased more frequently than SGOT, SGPT or total bilirubin. The majority of these abnormalities regress spontaneously during the course of treatment.
Pain and asthenia were the most frequently reported miscellaneous adverse effects; their relationship to the tumor and to anemia was likely. Alopecia was reported (3%). Cardiovascular, respiratory, genitourinary and mucosal side effects have occurred in 6% or less of the patients. Cardiovascular events (cardiac failure, embolism, cerebrovascular accidents) were fatal in less than 1%of the patients and did not appear to be related to chemotherapy. Cancer-associated hemolytic uremic syndrome has been reported rarely.