High-Dose (480 mg/day) Tamoxifen with Etoposide: A Study of a Potential Multi-Drug Resistance ModulatorMillward M.J.a · Lien E.A.b · Robinson A.a · Cantwell B.M.J.a
aUniversity Department of Clinical Oncology, Newcastle General Hospital, Newcastle Upon Tyne, England, and bDepartment of Pharmacology and Toxicology, University of Bergen, Norway
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Tamoxifen and its principle metabolite N-desmethyltamoxifen can modulate multi-drug resistance in vitro. Tamoxifen 480 mg/day was given for 6 days with oral etoposide on days 4-6 to 17 patients with advanced solid tumours. Venous thrombosis (2 patients), reversible neurological toxicity (1 patient), and WHO grade III nausea/vomiting (3 patients) related to tamoxifen were observed but overall toxicity was manageable. One partial response occurred in 15 assessable patients. Mean plasma concentrations of tamoxifen and N-desmethyltamoxifen increased to 4.3 μmol/l and 2.7 μmol/l, respectively, by day 6. Plasma concentrations corresponding to active in vitro levels were attained by most patients.
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