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 losoxantrone (DuP-941), an anthrapyrazole, in patients with metastatic hormone-refractory prostate cancer. Patients with metastatic prostate cancer progressing on androgen ablation therapy without demonstrable antiandrogen withdrawal response were treated with losoxantrone 50 mg/m2 i.v. bolus every 21 days. All of the patients had elevated serum prostate-specific antigen (PSA) before study entry and had no prior chemotherapy. Forty-three assessable 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 serum PSA, 173 microg/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 in the serum PSA. Two of nine patients with measurable disease had partial responses and three had minor responses. Thirty percent of patients had improvement in KPS and 37% had an improvement in symptoms with decrease in pain and/or decrease in analgesic requirement. Nonhematological grade 3 and 4 toxicities were one each of grade 3 headache, grade 4 hypocalcemia, grade 3 hyperbilirubinemia, and grade 3 dyspnea. Twenty-six patients (60%) had grade 3 or 4 absolute neutropenia. In conclusion, losoxantrone demonstrated a partial biochemical response rate of 25%, response in measurable disease sites in 22%, and improvement in clinical symptoms in one-third of patients. In this study, PSA increase was not necessarily associated with lack of palliative response.
Huan
S D
SD
Ottawa Regional Cancer Centre, Ontario Cancer Treatment and Research Foundation and University of Ottawa, Ontario, Canada.
Natale
R B
RB
Stewart
D J
DJ
Sartiano
G P
GP
Stella
P J
PJ
Roberts
J D
JD
Symes
A L
AL
Finizio
M
M
D000368:Aged; D000369:Aged, 80 and over; D000855:Anorexia / Q000139:chemically induced; D000880:Anthraquinones / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary; D003967:Diarrhea / Q000139:chemically induced; D019008:Drug Resistance, Neoplasm; D005500:Follow-Up Studies; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D006402:Hematologic Diseases / Q000139:chemically induced; D006728:Hormones / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D047069:Pyrazolones; D013280:Stomatitis / Q000139:chemically induced; D016019:Survival Analysis; D014839:Vomiting / Q000139:chemically induced
D000880:Anthraquinones; D000970:Antineoplastic Agents; D006728:Hormones; D011720:Pyrazoles; D047069:Pyrazolones; C050637:losoxantrone; D017430:Prostate-Specific Antigen