THE CARDIOPROTECTOR ADR-529 AND HIGH-DOSE EPIRUBICIN GIVEN IN COMBINATION WITH CYCLOPHOSPHAMIDE, 5-FLUOROURACIL, AND TAMOXIFEN - A PHASE-I STUDY IN METASTATIC BREAST-CANCER

The purpose of this study was to determine the maximal tolerable dose (MTD) of epirubicin and ADR-529 given in combination with cyclophospha mide, 5-fluorouracil, and tamoxifen. A total of 64 breast cancer patie nts with locally advanced disease or a first metastatic event were inc luded. Using fixed doses of cyclophosphamide, 5-fluorouracil, and tamo xifen, cohorts of ten patients were treated with escalating doses of e pirubicin and ADR-529. With the use of protocol criteria specifying ev aluation after the first course, the MTD was not reached. Dose reducti ons carried out due to hematologic toxicity during the first four cour ses made it impossible to escalate doses of epirubicin beyond 80 mg/m( 2) given together with ADR-529 600 mg/m(2). The vascular toxicity of A DR-529 necessitated central venous access in a number of patients. For phase m evaluation of ADR-529 given together with cyclophosphamide, e pirubicin, 5-fluorouracil, and tamoxifen (CEF/TAM) we re commend using epirubicin/ADR-529 at 60/600 mg/m(2) Together with evaluation of the cardioprotective properties of ADR-529, we recommend evaluating the im pact of ADR-529 on the efficacy of cytotoxic therapy and investigating further the toxicity of ADR-529.