A reassessment of cardiac toxicity associated with Taxol.
Cardiac toxicity was first noted in patients receiving Taxol during continuous cardiac monitoring, which was performed because of the high incidence of serious hypersensitivity reactions noted early in phase I trials. After cardiac events were documented, patients with cardiac disease and those on medications known to alter cardiac conduction were excluded from most trials. The cardiac events reported with Taxol from the initiation of NCI-sponsored clinical trials through August 1992 are summarized. Adverse cardiac events were reviewed in four clinical databases: 1) the Cancer Therapy Evaluation Program's Adverse Drug Reaction database following treatment of more than 3400 patients; 2) all cardiac toxicities in patients on GOG-111 who were randomized to cisplatin plus either Taxol or cyclophosphamide; 3) cardiac toxicity in 198 patients who received 618 courses of Taxol with or without cisplatin during continuous cardiac monitoring; and 4) cardiac toxicities reported for the first 696 patients on NCI TRC-9103 for ovarian cancer. Published reports of studies of taxine's cardiac effects, and of cardiac toxicity associated with yew poisoning, Cremophor EL, and H1 and H2 antagonists, are also reviewed. In patients without significant cardiac risk factors, asymptomatic sinus bradycardia is frequent (approximately 30%). Heart block and conduction abnormalities occur infrequently and are often asymptomatic. The casual relationship of Taxol to atrial and ventricular arrhythmias and cardiac ischemia is less clear because many patients had other conditions known to be associated with cardiac events. Nevertheless, the incidence of serious cardiac events was low. Routine cardiac monitoring is not required for patients without risk factors. There are, however, insufficient data to make treatment recommendations for patients with cardiac disease and those taking medications that alter cardiac conduction. To maximize patient safety and the clinical database, physicians who administer Taxol should continue to be alert to potential cardiac toxicities associated with Taxol.