[.
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Action/Kinetics:
Binds to DNA and causes production of intrastrand cross-links and formation of DNA adducts. The drug is cell-cycle nonspecific.
t
1/2, plasma: 20-30 min.
Terminal t
1/2, blood cells: 36-47 days. Incomplete urinary excretion (only 35%-51% after 5 days). Concentrates in liver, kidneys, and large and small intestines, with low penetration of CNS. Over 90% bound to plasma protein.
Uses:
Palliative therapy. Combination therapy in metastatic testicular tumors and for metastatic ovarian tumors (e.g., with cyclophosphamide) in those who have received appropriate surgical or radiotherapeutic procedures. Single agent in metastatic ovarian tumors as secondary therapy in those refractive to standard therapy who have not previously received cisplatin. Single agent in transitional cell bladder cancer that is no longer amenable to surgery or radiotherapy.
Additional Contraindications:
Lactation. Preexisting renal impairment, myelosuppression, impaired hearing, history of allergic reactions to platinum compounds.
Additional Side Effects:
Renal: Severe cumulative renal toxicity, including renal tubular damage and renal insufficiency.
Electrolytes: Low levels of calcium, magnesium, potassium, phosphate, and sodium.
Neurologic: Seizures, taste loss, peripheral neuropathies. Neurotoxicity may occur 4-7 months after prolonged therapy.
Otic: Ototoxicity characterized by tinnitus, especially in children.
Ophthalmologic: Papilledema, cerebral blindness, optic neuritis. High doses have resulted in blurred vision and altered color perception.
Miscellaneous:
Anaphylactic reactions hyperuricemia.
Laboratory Test Alterations:
Plasma iron levels. Nephrotoxicity results in
serum uric acid, BUN, and creatinine and
C
CR.
Overdose Management:
Symptoms: Liver and kidney failure, deafness, ocular toxicity (including retinal detachment), significant myelosuppression, intractable N&V;, neuritis, death.
Treatment: General supportive measures.
Additional Drug Interactions:
-
Aminoglycosides / Cumulative nephrotoxity
-
Anticonvulsants / Anticonvulsant plasma levels may become subtherapeutic
-
Loop diuretics / Additive ototoxicity
-
Phenytoin /
Phenytoin effect R/T
plasma levels
How Supplied:
Injection: 1 mg/mL
Dosage
?IV only
Metastatic testicular tumors.
20 mg/m
2/day for 5 days/cycle.
Metastatic ovarian tumors.
Cisplatin: 75-100 mg/m
2 once every 4 weeks/cycle. Cyclophosphamide: 600 mg/m
2 once every 4 weeks on day 1. Administer cisplatin and cyclophosphamide sequentially.
Advanced bladder cancer.
50-70 mg/m
2 per cycle once q 3-4 weeks, depending on prior radiation or chemotherapy. For those heavily pretreated, give an initial dose of 50 mg/m
2/cycle repeated q 4 weeks.
NOTE: Repeat courses should not be administered until (1) serum creatinine is below 1.5 mg/dL and/or the BUN is below 25 mg/dL; (2) platelets are equal to or greater than 100,000/mm
3 and leukocyte count is equal to or greater than 4,000/mm
3; and (3) auditory activity is within the normal range.
