Hudes G R, Greenberg R, Krigel R L, Fox S, Scher R, Litwin S, Watts P, Speicher L, Tew K, Comis R
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.
J Clin Oncol. 1992 Nov;10(11):1754-61. doi: 10.1200/JCO.1992.10.11.1754.
Estramustine phosphate (EMP) and vinblastine are two microtubule inhibitors with distinct molecular targets and at least additive antimicrotubule effects in vitro. Their modest single-agent activities in hormone-refractory prostate cancer, nonoverlapping toxicities, and lack of cross-resistance prompted a phase II trial in hormone-refractory prostate cancer.
Thirty-six assessable patients at the Fox Chase Cancer Center and seven Fox Chase Cancer Center Network institutions were treated with oral EMP 600 mg/m2 on days 1 to 42 and vinblastine 4 mg/m2 intravenously (IV) once a week for 6 weeks. Courses were repeated every 8 weeks. Response assessment was based on a change in serum prostate-specific antigen (PSA) levels and was correlated with change in pain scores.
PSA decreased from baseline by at least 50% in 22 patients (61.1%) and by > or = 75% in eight patients (22.2%). A 50% or more decrease in PSA on three successive 2-week measurements together with an improved or stable pain score, performance status, and measurable soft tissue disease (if present) was required for a partial response (PR), which occurred in 11 patients for an overall response rate of 30.5% (95% confidence interval, 15.6% to 45.6%). In seven patients with measurable nonosseous disease, there was one PR (14%) and one minor response (MR). In 28 patients with assessable pain, major pain responses occurred in 12 (42.9%). PSA response (> or = 50% decrease times three measurements) was predictive of major pain response with a 93.7% specificity, a 50% sensitivity, and a positive predictive value of 85.7%.
We conclude that EMP and vinblastine is an active combination in hormone-refractory prostate cancer.
磷酸雌莫司汀（EMP）和长春碱是两种微管抑制剂，它们具有不同的分子靶点，在体外至少具有相加的抗微管作用。它们在激素难治性前列腺癌中的单药活性适中、毒性不重叠且不存在交叉耐药性，因此开展了一项针对激素难治性前列腺癌的II期试验。
福克斯蔡斯癌症中心及七个福克斯蔡斯癌症中心网络机构的36例可评估患者接受治疗，第1至42天口服EMP 600 mg/m²，长春碱4 mg/m²静脉注射，每周1次，共6周。每8周重复一个疗程。疗效评估基于血清前列腺特异性抗原（PSA）水平的变化，并与疼痛评分的变化相关。
22例患者（61.1%）的PSA较基线水平降低至少50%，8例患者（22.2%）降低≥75%。部分缓解（PR）要求连续3次2周测量时PSA降低50%或更多，同时疼痛评分、体能状态及可测量的软组织疾病（若存在）改善或稳定，11例患者出现PR，总缓解率为30.5%（95%置信区间，15.6%至45.6%）。7例有可测量非骨疾病的患者中，有1例PR（14%）和1例轻微缓解（MR）。28例有可评估疼痛的患者中，12例（42.9%）出现主要疼痛缓解。PSA缓解（≥50%降低且测量3次）对主要疼痛缓解具有预测性，特异性为93.7%，敏感性为50%，阳性预测值为85.7%。
我们得出结论，EMP和长春碱联合用药对激素难治性前列腺癌有效。
