Huan S D, Natale R B, Stewart D J, Sartiano G P, Stella P J, Roberts J D, Symes A L, Finizio M
Ottawa Regional Cancer Centre, Ontario Cancer Treatment and Research Foundation and University of Ottawa, Ontario, Canada.
Clin Cancer Res. 2000 Apr;6(4):1333-6.
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.
我们开展这项研究的目的是确定蒽吡唑类药物洛索蒽醌（DuP - 941）对转移性激素难治性前列腺癌患者的疗效和毒性。接受雄激素剥夺治疗后病情进展且无明显抗雄激素撤药反应的转移性前列腺癌患者，接受洛索蒽醌50 mg/m²静脉推注，每21天一次。所有患者在研究入组前血清前列腺特异性抗原（PSA）均升高，且未曾接受过化疗。43例可评估患者入组。中位年龄为70.6岁（范围53.9 - 85.9岁），中位卡诺夫斯基功能状态评分（KPS）为70%（50 - 90%），中位血清PSA为173 μg/升（12.5 - 11,140）。中位疗程数为4（1 - 9）。5例患者（25%）出现部分缓解，定义为血清PSA下降>50%。9例可测量病灶患者中有2例出现部分缓解，3例出现轻微缓解。30%的患者KPS有所改善，37%的患者症状有所改善，疼痛减轻和/或镇痛需求减少。非血液学3级和4级毒性反应分别为1例3级头痛、1例4级低钙血症、1例3级高胆红素血症和1例3级呼吸困难。26例患者（60%）出现3级或4级绝对中性粒细胞减少。总之，洛索蒽醌的部分生化缓解率为25%，可测量病灶部位的缓解率为22%，三分之一的患者临床症状有所改善。在本研究中，PSA升高不一定与缺乏姑息性反应相关。
