A multicenter phase II trial of losoxantrone (DuP-941) in hormone-refractory metastatic prostate cancer

Our purpose in this study was to determine the efficacy and toxicity of los oxantrone (DuP-941), an anthrapyrazole, in patients with metastatic hormone -refractory prostate cancer. Patients with metastatic prostate cancer progr essing on androgen ablation therapy without demonstrable antiandrogen withd rawal response were treated with losoxantrone 50 mg/m(2) i.v. bolus every 2 1 days. All of the patients had elevated serum prostate-specific antigen (P SA) before study entry and had no prior chemotherapy, Forty-three assessabl e patients were entered. The median age was 70.6 years (range, 53.9-85.9), median Karnofsky performance scale (KPS), 70% (50-90%), and the median seru m PSA, 173 mu g/liter (12.5-11.140). The median number of courses was 4 (1- 9). Five patients (25%) had a partial response as defined by >50% decline i n the serum PSA. Two of nine patients with measurable disease had partial r esponses and three had minor responses. Thirty percent of patients had impr ovement in KPS and 37% had an improvement in symptoms with decrease in pain and/or decrease in analgesic requirement. Nonhematological grade 3 and 4 t oxicities were one each of grade 3 headache, grade 4 hypocalcemia, grade 3 hyperbilirubinemia, and grade 3 dyspnea. Twenty-six patients (60%) had grad e 3 or 4 absolute neutropenia, In conclusion, losoxantrone demonstrated a p artial biochemical response rate of 25%, response in measurable disease sit es in 22%, and improvement in clinical symptoms in one-third of patients, I n this study, PSA increase was not necessarily associated with lack of pall iative response.