Drug Interactions between cisplatin and Erbitux

MONITOR: The safety of cetuximab in combination with cisplatin and radiation therapy has not been established. Death and serious cardiotoxicity were observed in a single-arm trial with cetuximab, cisplatin (100 mg/m2), and delayed, accelerated (concomitant boost) fractionation radiation therapy conducted in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Two of 21 patients died, one from pneumonia and one from an unknown cause. Four patients discontinued treatment due to adverse events, two of which were cardiac events (myocardial infarction in one and arrhythmia, diminished cardiac output, and hypotension in the other). An integrated analysis across all clinical studies demonstrated that cisplatin does not affect the pharmacokinetics of cetuximab. In a controlled study of 940 patients with locally advanced SCCHN, the addition of cetuximab to cisplatin and radiation resulted in an increase in the incidence of grade 3 or 4 mucositis, radiation recall syndrome, acneiform rash, cardiac events, and electrolyte disturbances compared to radiation and cisplatin alone. Adverse reactions with fatal outcome were reported in 4.4% versus 3.0%, and myocardial ischemia in 2.0% versus 0.9%, of patients in the cetuximab combination arm compared to the control arm. The addition of cetuximab to radiation and cisplatin did not improve progression-free survival.

MANAGEMENT: Until more data are available, caution is advised if cetuximab is used in combination with cisplatin and/or radiation, particularly in patients with a history of coronary artery disease, congestive heart failure, or arrhythmias. Patients should be monitored closely for cardiotoxicity, and therapy discontinued if necessary.