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JNCI Journal of the National Cancer Institute 1991 83(2):105-110; doi:10.1093/jnci/83.2.105
© 1991 by Oxford University Press
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Journal of the National Cancer Institute, Vol. 83, No. 2, 105-110, January 16, 1991
© 1991 Oxford University Press

Systemic Toxic Effects Associated With High-Dose Verapamil Infusion and Chemotherapy Administration

Gregory D. Pennock, William S. Dalton*, William R. Roeske, Christopher P. Appleton, Kurt Mosley, Patricia Plezia, Thomas P. Miller, Sydney E. Salmon

Department of Internal Medicine, University of Arizona Tucson, Ariz
Public Health Service grants CA-43043 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services
Public Health Service grants CA-17094 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services

*Correspondence to: William S. Dalton, MD, PhD, Department of Internal Medicine, University of Arizona Cancer Center, College of Medicine, 1515 N Campbell, Tucson, AZ 85724

Aside from its more conventional uses as a cardiovascular drug, the calcium channel blocker verapamil has recently been added to chemotherapeutic regimens to reduce drug resistance in B-cell and other neoplasms that express the P-glyco-protein. We recently treated patients with continuous-infusion verapamil (0.15 mg/kg per hour to 0.60 mg/kg per hour) over a 5-day period in combination with continuous-infusion vincristine and doxorubicin plus oral dexamethasone. Seventy-one courses involving 35 hospitalized patients were prespectively studied for cardiovascular and other side effects. Cardiovascular side effects were observed most frequently and consisted of first-degree heart block, hypotension, sinus bradycardia, and junctional rhythms. We observed higher degree heart block, but the QRS interval remained narrow and the ventricular escape rate remained relatively normal. Effects on mean arterial pressure, heart rate, and PR interval were both time and dose related. Severe, symptomatic congestive heart failure was rarely observed. The most common noncardiovascular side effects were constipation, peripheral edema, and weight gain. All systemic toxic effects observed were easily treated or disappeared with either temporary or permanent discontinuation of the verapamil infusion or by a decrease in the dose of verapamil. We conclude that the cardiovascular side effects associated with continuous, high-dose intravenous verapamil therapy are significant and dose limiting but are rapidly reversible. Less cardiotoxic chemosensitizers are needed to reverse multidrug resistance in cancer. [J Natl Cancer Inst 83:105–110,1991]


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