Cisplatin, Alkylating Agent
is an inorganic complex formed by an atom of
platinum surrounded by
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.
limiting side-effects: nausea and vomiting, peripheral neuropathy,
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.
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.
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
of audiogram abnormalities in 24% of patients.
common: nausea/vomiting, kidney, neuropathy