Cisplatin

Myelosuppression is a major dose-related toxicity.

Cisplatin is a vesicant at higher concentrations, and an irritant at lower concentrations; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. Local infusion site reactions may occur; monitor infusion site during administration.

Nausea and vomiting are dose-related toxicities. Cisplatin is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016). Nausea and vomiting are dose-related and may be immediate and/or delayed. Diarrhea may also occur.

Anaphylactic-like reactions have been reported; may include facial edema, bronchoconstriction, tachycardia, and hypotension and may occur within minutes of administration. Symptoms may be managed with epinephrine, corticosteroids, and/or antihistamines.

Hyperuricemia has been reported with cisplatin use, and is more pronounced with doses >50 mg/m2; consider antihyperuricemic therapy to reduce uric acid levels.

Severe (and possibly irreversible) neuropathies (including stocking-glove paresthesias, areflexia, and loss of proprioception/vibratory sensation) may occur with higher than recommended doses or more frequent administration; may require therapy discontinuation. Seizures, loss of motor function, loss of taste, leukoencephalopathy, and posterior reversible leukoencephalopathy syndrome (PRES [formerly RPLS]) have also been described.

Ototoxicity, which may be more pronounced in children, is manifested by tinnitus and/or loss of high frequency hearing and occasionally deafness; may be significant. Ototoxicity is cumulative and may be severe. Audiometric testing should be performed at baseline and prior to each dose. Certain genetic variations in the thiopurine S-methyltransferase (TPMT) gene may be associated with an increased risk of ototoxicity in children administered conventional cisplatin doses (Pussegoda 2013). Controversy may exist regarding the role of TPMT variants in cisplatin ototoxicity (Ratain 2013; Yang 2013); the association has not been consistent across populations and studies. Children without the TPMT gene variants may still be at risk for ototoxicity. Cumulative dose, prior or concurrent exposure to other ototoxic agents (eg, aminoglycosides, carboplatin), prior cranial radiation, younger age, and type of cancer may also increase the risk for ototoxicity in children (Knight 2005; Landier 2014). Pediatric patients should receive audiometric testing at baseline, prior to each dose, and for several years after discontinuing therapy. An international grading scale (SIOP Boston scale) has been developed to assess ototoxicity in children (Brock 2012).

Cumulative renal toxicity associated with cisplatin is severe. Monitor serum creatinine, blood urea nitrogen, creatinine clearance, and serum electrolytes (calcium, magnesium, potassium, and sodium) closely. According to the manufacturer’s labeling, use is contraindicated in patients with preexisting renal impairment and renal function must return to normal prior to administering subsequent cycles; some literature recommends reduced doses with renal impairment. Nephrotoxicity may be potentiated by aminoglycosides.

Secondary malignancies have been reported with cisplatin in combination with other chemotherapy agents. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Select dose cautiously and monitor closely in elderly patients; they may be more susceptible to nephrotoxicity and peripheral neuropathy. Other warnings/precautions:

Doses >100 mg/m2/cycle (once every 3 to 4 weeks) are rare; verify with the prescriber. Exercise caution to avoid inadvertent overdose due to potential sound-alike/look-alike confusion between CISplatin and CARBOplatin or prescribing practices that fail to differentiate daily doses from the total dose per cycle. At the approved dose, cisplatin should not be administered more frequently than once every 3 to 4 weeks.

Should be administered under the supervision of an experienced cancer chemotherapy physician. Adequate diagnostic and treatment facilities and appropriate management of potential complications should be readily available.

Patients should receive adequate hydration, with or without diuretics, prior to and for 24 hours after administration; serum electrolytes, particularly magnesium and potassium, should be monitored and replaced as needed during and after therapy.