Dose-related and cumulative renal insufficiency associated with renal tubular damages the major dose-limiting toxicity of Cisplatin. A single dose of 50 mg/m2
BSA has caused renal toxicity in 28 - 36% patients. Elevations in BUN and creatinine, serum uric acid and/or a decrease in creatinine clearance are first sign during the second week after the dose. Renal function must return to normal before the next dose of Cisplatin can be given.
Manifested by tinnitus and/or loss of hearing in the high frequency range. Decreased ability to hear normal conversational tones may occur occasionally. Hearing loss can be unilateral or bilateral. A single dose of 50 mg/m2
BSA has caused ototoxicity in up to 31% of patients. Cisplatin induced ototoxicity in up to 31% of patients. Cisplatin induced ototoxicity is cumulative, may be more severe in children and it is unclear whether reversible or not.
Dose-related myelosuppression occurs in 25 - 30% of patients. The lowest platelet and leukocyte counts occur between days 18 - 23 (ranges 7.5 - 45). Most patients recover by day 39 (range 13 - 62). Anemia (decrease of > 2 g Hb/100 mL) occurs at approximately the same frequency and with the same timing as leucopenia and thrombocytopenia.
Marked nausea and vomiting occur in almost all patients and are occasionally so severe that the drug must be discontinued. Nausea and vomiting usually begin within 1 - 4 hours after treatment and last up to 24 hours. Various degrees of nausea and anorexia may persist up to one week after treatment.
Has occurred in some patients. It is usually manifested by peripheral neuropathies and rarely by optic neuritis, papilledema, cerebral blindness, loss of appetite and seizures. Cisplatin induced neuropathies may occur after prolonged therapy (4 - 7 months), but may also occur after a single dose. The drug should be discontinued when the symptoms are first observed. Improvement and/or total recovery usually occurs. In some patients, however, peripheral neuropathy may be irreversible.
Have been occasionally reported in patients previously exposed to Cisplatin. The reactions consist of facial edema, wheezing, tachycardia and hypotension within a few minutes or drug administration.
Serum electrolyte disturbances:
Hypocalcemia, hypokalemia and hypophosphatemia have occurred and are probably related to renal tubular damage. Tetany has occasionally accompanied hypocalcemia and hypomagnesemia. Discontinuation usually restores the serum electrolyte levels to normal.
Occurs at approximately the same frequency as the increased in BUN and serum creatinine. It peaks between 3 - 5 days after the dose. Allopurinol therapy effectively reduces uric acid levels.
Other toxicities which rarely occurred are cardiac abnormalities, anorexia and elevated SGOT.