I have started a new chemotherapy job and the staff does not add potassium magnesium and mannitol to the hydration regimens for cisplatin, even at 200 mg IV doses of cisplatin. I haven’t ever heard of not adding these drugs. Is there any evidence to support adding or not adding these agents to the hydration for cisplatin?
Cisplatin is used for the treatment of many cancers. One dose-limiting adverse effect of cisplatin is nephrotoxicity. Cisplatin is predominantly excreted by the kidneys, and concentrations in the kidneys are higher than in the blood or other tissues. As a result, the tubular epithelial cells of the proximal renal tubules may be damaged. Cisplatin also causes nephrotoxicity by causing vasoconstriction in the renal microvasculature, reduced renal blood flow, and expression of pro-inflammatory cytokines.
Nephrotoxicity due to cisplatin is cumulative and associated with higher doses and duration of therapy. The risk of nephrotoxicity may also be increased by concomitant administration of other nephrotoxic medications (eg, the aminoglycoside antibiotics) in patients with pre-existing renal dysfunction, or in elderly or pediatric patients. Patients may experience impaired renal function, affecting clearance of cisplatin and other medications, elevations in serum creatinine (SCr) and blood urea nitrogen (BUN), and may also experience electrolyte wasting. Alterations in serum electrolytes including hypomagnesemia, hypokalemia, hyponatremia, hypocalcemia, and hypophosphatemia have been reported in studies evaluating various doses of cisplatin.
Patients should be monitored for nephrotoxicity at baseline and prior to each dose of cisplatin, with labs including SCr, BUN, and electrolytes such as potassium and magnesium.1 To reduce the risk of nephrotoxicity, it is recommended that patients be hydrated with 1 to 2 liters of IV fluids. Hydration is recommended to induce diuresis and reduce the concentration of cisplatin in the kidneys. Isotonic saline (0.9% sodium chloride) is recommended for hydration fluids, and many centers also include potassium and magnesium in these hydration fluids due to the risk of electrolyte wasting.
Mannitol and furosemide have also been used to increase diuresis, although there are not clinical studies demonstrating that these interventions are superior to hydration alone. Some references recommend that cisplatin be infused over several hours in solution with mannitol,2 however this duration of cisplatin infusion is not appropriate for many chemotherapy regimens.