QUINIDINE AS A RESISTANCE MODULATOR OF EPIRUBICIN IN ADVANCED BREAST CANCER : MATURE RESULTS OF A PLACEBO-CONTROLLED RANDOMIZED TRIAL

PURPOSETo evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer.PATIENTS AND METHODSBetween 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses.RESULTSTen eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anth...