EPIRUBICIN COMBINED WITH ESTRAMUSTINE PHOSPHATE IN HORMONE-RESISTANT PROSTATE-CANCER - A PHASE-II STUDY

Twenty-four assessable patients with hormone-resistant prostate cancer (HRPC) were to receive daily doses of oral estramustine phosphate (EM P), 10 mg kg(-1), and intravenous epirubicin (EPR) infusions, 100 mg m (-2), every third week up to a cumulative dose of 500 mg m(-2). Bioche mical response [greater than or equal to 50% reduction in pretreatment serum prostate-specific antigen (PSA) after three cycles of greater t han or equal to 3 weeks' duration] was demonstrated in 13 of 24 patien ts included (54%). No objective response (WHO criteria) was observed, although seven of nine evaluable patients achieved a greater than or e qual to 50% serum PSA reduction. Subjective improvement (pain score, p erformance status) occurred in 7 of 24 patients, whereas nine patients progressed subjectively. There was no correlation between subjective and biochemical response. Biochemical progression (greater than or equ al to 50% increase of nadir PSA) occurred after a median of 12 weeks. All but two patients were alive after a median follow-up time of 8.7 m onths for surviving patients (range 3.3-13.2). Eight patients experien ced grade 3/4 leucopenia, with no indication of cumulative myelosuppre ssion. Cardiovascular toxicity was experienced by four patients. Two p atients developed angioedema twice, in one patient requiring hospitali zation at the intensive ward. Based on this limited series, the combin ation of EPR and EMP in patients with HRPC is tolerable and appears to be effective in terms of significant PSA reduction. The results warra nt further investigations of the two drugs and, in particular, of the clinical significance of greater than or equal to 50% PSA decrease in patients with HRPC.