HIGH-DOSE (480 MG DAY) TAMOXIFEN WITH ETOPOSIDE - A STUDY OF A POTENTIAL MULTIDRUG-RESISTANCE MODULATOR/

Tamoxifen and its principle metabolite N-desmethyltamoxifen can modula te 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 so lid tumours. Venous thrombosis (2 patients), reversible neurological t oxicity (1 patient), and WHO grade III nausea/vomiting (3 patients) re lated to tamoxifen were observed but overall toxicity was manageable. One partial response occurred in 15 assessable patients. Mean plasma c oncentrations of tamoxifen and N-desmethyltamoxifen increased to 4.3 m u mol/l and 2.7 mu mol/l, respectively, by day 6. Plasma concentration s corresponding to active in vitro levels were attained by most patien ts.