Cisplatin, Alkylating Agent

• Cisplatin is an inorganic complex formed by an atom of platinum surrounded by chlorine and ammonia atoms in the cis position of a horizontal plane. Intracellularly, water displaces the chloride to form highly reactive charged platinum complexes. These complexes inhibit DNA through covalent binding leading to intrastrand, interstrand, and protein cross-linking of DNA. Experimental and clinical data suggest that cisplatin enhances radiation therapy effects. Early studies suggested that cisplatin was cell cycle phase-nonspecific, while more recent studies have shown complex and variable effects on the cell cycle.
• Dose limiting side-effects: nausea and vomiting, peripheral neuropathy, toxic nephropathy
• Severe nausea/vomiting in almost all patients
• Tubular necrosis of both proximal and distal renal tubules occurs. It is cumulative and occurs in 28-36% of patients. Nephrotoxicity can be minimized or prevented by IV hydration and mannitol diuresis. Furosemide diuresis is theoretically hazardous due to potential additive ototoxicity. Serum creatinine concentration is an inadequate indicator of nephrotoxicity in children. Nuclear medicine GFR measurement is preferred, when this test is available. Renal tubular abnormality such as acidosis, hypomagnesemia or hypokalemia may be present with normal glomerular function.
• Hypomagnesemia (magnesium wasting) may become severe enough to cause tetany. Monitor serum magnesium and supplement orally or intravenously as required. Hypomagnesemia may persist for greater than one year following treatment.
• Neurotoxicity consists of peripheral neuropathies which are sensory in nature but can also include motor difficulties, reduced deep-tendon reflexes and leg weakness. Symptoms usually occur after prolonged therapy (4-7 months) and may be irreversible. Seizures, altered taste, slurred speech, and memory loss have occurred rarely. Cisplatin should be discontinued if functionally important neuropathy develops.
• Ototoxicities consist of audiogram abnormalities in 24% of patients.
• Most common: nausea/vomiting, kidney, neuropathy