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Intermittent high-dose tamoxifen as a potential modifier of multidrug resistance

Authors
Journal
European Journal of Cancer
0959-8049
Publisher
Elsevier
Publication Date
Volume
28
Identifiers
DOI: 10.1016/0959-8049(92)90119-m

Abstract

Abstract In vitro tamoxifen reverses multidrug resistance (MDR). To evaluate the clinical potential of using tamoxifen in this way, intermittent high-dose tamoxifen was combined with oral etoposide in 86 patients. At 320 mg/day tamoxifen for 6 days, mean plasma levels of tamoxifen in 11 patients increased from 453 ng/ml (range 269–664) on day 2 to 984 ng/ml (578–1336) on day 6. Of 31 patients who had plasma tamoxifen measured during the time of etoposide administration (days 4–6), 13 (43%) were over 1111 ng/ml (3 μmol/l), an active in vitro level. Potentially active levels of the principal metabolite, N-desmethyl tamoxifen, were also obtained but accumulation was slower. Emesis and thromboembolism were toxicities. Tamoxifen is a modifier of MDR, a role that warrants further clinical studies.

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