Treatment of Metastatic Hormone Refractory Prostate Cancer with Ketoconazole, Hydrocortisone, and Cyclophosphamide

A. Pecora, F. Richter, A. Pavlick, V. Lanteri, John Scheuch, S. Levy, G. Rosenberg, J. Vitenson
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Abstract

Objective: Patients with metastatic hormone-refractory prostate cancer have a poor overall survival rate. Newer agents have shown promise in slowing disease progression but are mostly ineffective in improving the overall survival rate, are toxic, and require intravenous administration. In an attempt to maintain treatment efficacy, but to minimize toxicity and improve ease of use, we conducted a pilot trial of an oral regimen consisting of ketoconazole, hydrocortisone, and cyclophosphamide combination therapy. Materials and Methods: Twenty-seven patients with metastatic hormone-refractory prostate cancer were treated with an oral regimen of ketoconazole, 400 mg tid, and hydrocortisone, 20 mg qam and 10 mg qpm, on Days 1–28. Cyclophosphamide, 100 mg/m2, was added on Days 1–14. Treatment was recycled every 28 days. Progression of disease was defined by a progressively rising prostate specific antigen (PSA) level, new lesions as seen on bone scans, or progression of soft-tissue disease. Patient age ranged from 57 to 87 years. Performance status (PS; Eastern Cooperative Oncology Group scale) was 0–2. Pretreatment PSA values ranged from 5.8 ng/mL to 3400 ng/mL (median 68). Results: Twenty-one (78%) of 27 patients with elevated PSA levels demonstrated a ≥50% decline in PSA level for 3 consecutive months. Of the remaining six patients (22%), two progressed within 3 months, two withdrew from the study due to toxicity, and two responded with 96 months, with a median response duration of 9 months. Twenty-two (81%) of 27 patients experienced no significant toxicity, 4 of 27 patients experienced Grade I–III gastrointestinal toxicity, and 1 of 27 patients experienced Grade III hematologic toxicity. Conclusions: The combination of ketoconazole, hydrocortisone, and cyclophosphamide is a well-tolerated oral regimen for the treatment of patients with metastatic hormone-refractory prostate cancer with significant disease activity, and it warrants further investigation.
酮康唑、氢化可的松和环磷酰胺治疗转移性激素难治性前列腺癌
目的:转移性激素难治性前列腺癌患者的总生存率较低。较新的药物在减缓疾病进展方面显示出希望,但在提高总体生存率方面大多无效,而且有毒性,需要静脉注射。为了保持治疗效果,同时尽量减少毒性和提高易用性,我们进行了一项由酮康唑、氢化可的松和环磷酰胺联合治疗的口服方案的试点试验。材料与方法:27例转移性激素难治性前列腺癌患者口服酮康唑400 mg tid,氢化可的松20 mg qam和10 mg qpm,第1-28天。第1-14天,添加环磷酰胺100 mg/m2。每28天循环一次。疾病进展的定义是前列腺特异性抗原(PSA)水平逐渐升高,骨扫描中出现新的病变,或软组织疾病进展。患者年龄57 ~ 87岁。性能状态(PS;东部肿瘤合作小组(Eastern Cooperative Oncology Group)评分为0-2。预处理PSA值从5.8 ng/mL到3400 ng/mL不等(中位数68)。结果:27例PSA水平升高患者中,21例(78%)连续3个月PSA水平下降≥50%。其余6例患者(22%)中,2例在3个月内进展,2例因毒性退出研究,2例在96个月内出现反应,中位反应持续时间为9个月。27例患者中有22例(81%)无明显毒性,27例患者中有4例出现I-III级胃肠道毒性,27例患者中有1例出现III级血液毒性。结论:酮康唑、氢化可的松、环磷酰胺联合治疗转移性激素难治性前列腺癌患者是一种耐受性良好的口服治疗方案,值得进一步研究。
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