Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study.
OBJECTIVE
The vascular endothelium plays a central role in the regulation of arterial vasomotor tone, releasing nitric oxide for vasodilation. Endothelial-dependent vasodilation can be assessed in vivo, using high resolution ultrasound to measure changes in diameter of the brachial artery. Animal studies have demonstrated that anthracyclines can damage the endothelium and impair the vasodilatory response of arteries; however, there are no comparable data in humans. This is a pilot study assessing endothelial toxicity from anthracyclines in pediatric cancer patients.


METHODS
Fourteen control patients and 14 cancer patients (4 to 21 years) were studied. Cancer patients had completed chemotherapy containing no less than 300 mg/m2 of anthracyclines 2 to 60 months before study. Brachial artery diameters were measured at rest and 1 minute after blood pressure cuff occlusion. Brachial artery reactivity (BAR) was calculated as percent change between baseline and after cuff deflation measurements. Results were compared using unpaired, two-tailed t-test.


RESULTS
Baseline characteristics, including age, percentage of females, blood pressure, and resting vessel diameters were similar between the two groups. BAR in the controls averaged 6.7% with a standard deviation (SD) of 3.3%, while BAR in patients receiving anthracyclines averaged 3.8% with an SD of 3.4%, demonstrating a significant decrease (P < .05) in vasomotor reactivity in the treated group.


CONCLUSIONS
These results suggest that anthracyclines cause impaired endothelial function, an important and newly recognized toxicity. Since endothelial dysfunction is an early event in atherogenesis, there may be important clinical implications from these findings. Further study is required to confirm these preliminary results in a larger cohort.
Department of Pediatrics, Lucile Salter Packard Children's Hospital, Stanford University, Stanford, CA 94304, USA.
Amy Y
AY
Chow
Clifford
C
Chin
Gary
G
Dahl
David N
DN
Rosenthal
D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003324:Coronary Artery Disease / Q000139:chemically induced; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D010865:Pilot Projects; D014463:Ultrasonography
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin