Pienta K J, Fisher E I, Eisenberger M A, Mills G M, Goodwin J W, Jones J A, Dakhil S R, Crawford E D, Hussain M H
University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Prostate. 2001 Mar 1;46(4):257-61. doi: 10.1002/1097-0045(20010301)46:4<257::aid-pros1031>3.0.co;2-4.
The combination of oral estramustine and oral etoposide has generated response rates of 40-50% in patients with hormone refractory prostate cancer in single institution trials. This study tested this regimen in a multi-institutional setting.
Fifty-five patients were accrued over a period of 4 months between 1 March 1996 and 1 July 1996. Two patients were not analyzable and two patients were ineligible. They were given an oral regimen consisting of estramustine 15 mg/kg/day (capped at 1120 mg per day) and etoposide 50 mg/M(2)/day, days 1-21 every 28 days. Patients received a median of two cycles of therapy.
Toxicities included 11 patients (20%) with grades 3 or 4 granulocytopenia, 5 patients (10%) with grades 3 or 4 edema, and 3 patients (6%) with a thrombotic event. There were two treatment-related deaths, one as a result of anemia and the other as a result of a myocardial infarction. Of the 32 men who received at least 2 cycles of therapy, 7 men (22%) demonstrated a partial response to this regimen as measured by prostate-specific antigen (PSA) criteria of a 50% decline from pretreatment values.
This trial demonstrates the toxicity of estramustine delivered in high dose. It also illustrates the difficulty of conducting phase II trials in prostate cancer in the cooperative group setting where the experience and comfort level of oncologists with new agents is less than that of the physicians at the institution where the therapy was developed. As the activity of this regimen with low-dose estramustine is defined, further multi-institutional studies may be warranted.
在单中心试验中，口服雌莫司汀与口服依托泊苷联合使用，使激素难治性前列腺癌患者的缓解率达到了40% - 50%。本研究在多中心环境中对该方案进行了测试。
在1996年3月1日至1996年7月1日的4个月期间，招募了55名患者。两名患者无法进行分析，两名患者不符合条件。他们接受了一种口服方案，即雌莫司汀15毫克/千克/天（每日上限为1120毫克）和依托泊苷50毫克/平方米/天，每28天的第1 - 21天用药。患者接受治疗的中位周期数为两个周期。
毒性反应包括11名患者（20%）出现3或4级粒细胞减少，5名患者（10%）出现3或4级水肿，3名患者（6%）发生血栓事件。有两例与治疗相关的死亡，一例死于贫血，另一例死于心肌梗死。在32名接受至少两个周期治疗的男性中，7名男性（22%）根据前列腺特异性抗原（PSA）标准显示对该方案有部分缓解，即较治疗前值下降50%。
该试验证明了高剂量雌莫司汀的毒性。它还说明了在协作组环境中进行前列腺癌II期试验的困难，在这种环境下，肿瘤学家对新药物的经验和熟悉程度低于开发该疗法的机构中的医生。随着低剂量雌莫司汀方案活性的明确，可能需要进一步的多中心研究。
