Hudes G R, Nathan F, Khater C, Haas N, Cornfield M, Giantonio B, Greenberg R, Gomella L, Litwin S, Ross E, Roethke S, McAleer C
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
J Clin Oncol. 1997 Sep;15(9):3156-63. doi: 10.1200/JCO.1997.15.9.3156.
To evaluate the antitumor activity of 96-hour paclitaxel and daily oral estramustine phosphate (EMP) in patients with metastatic hormone-refractory prostate cancer (HRPC).
Thirty-four patients with adenocarcinoma of the prostate that progressed after one or more hormonal therapies and a trial of antiandrogen withdrawal were enrolled onto this phase II trial. Patients received paclitaxel 120 mg/m2 by 96-hour intravenous (i.v.) infusion on days 1 through 4 of each 21-day cycle, together with daily oral EMP 600 mg/m2/d, continuously.
Four of nine patients with measurable disease had objective responses (one complete response [CR] and three partial responses [PRs]) in liver (two patients) or nodes (two patients) of 2, 6, 8, and 20 months' duration. Of 25 assessable patients with metastases limited to bone, 14 had a > or = 50% decline in pretreatment prostate-specific antigen (PSA) level sustained for at least 6 weeks and seven had a > or = 80% decline. Overall, 17 of 32 patients (53.1%) with elevated pretreatment PSA levels had a > or = 50% decline of PSA and nine (28.1%) had a > or = 80% decrease. The main toxicities (> or = grade 2) were nausea, fluid retention, and fatigue, which occurred in 33%, 33%, and 24.2% of patients. Median time to progression, based on increasing PSA level and other clinical criteria, was 22.5 weeks. The estimated median overall survival time is 69 weeks.
The combination of EMP and 96-hour paclitaxel is an active regimen for patients with HRPC. These results further support the therapeutic strategy of combining agents that impair microtubule function by complementary mechanisms.
评估96小时静脉滴注紫杉醇联合每日口服磷酸雌莫司汀（EMP）治疗转移性激素难治性前列腺癌（HRPC）患者的抗肿瘤活性。
34例前列腺腺癌患者在接受一种或多种激素治疗及抗雄激素撤药试验后病情进展，纳入该II期试验。患者在每21天周期的第1至4天接受96小时静脉输注紫杉醇120mg/m²，同时每日口服EMP 600mg/m²/d，持续给药。
9例可测量病灶的患者中有4例出现客观缓解（1例完全缓解[CR]和3例部分缓解[PR]），分别出现在肝脏（2例患者）或淋巴结（2例患者），缓解持续时间为2、6、8和20个月。25例可评估的骨转移患者中，14例患者前列腺特异性抗原（PSA）水平较治疗前下降≥50%，且持续至少6周，7例患者下降≥80%。总体而言，32例治疗前PSA水平升高的患者中，17例（53.1%）PSA水平下降≥50%，9例（28.1%）下降≥80%。主要毒性反应（≥2级）为恶心、液体潴留和疲劳，分别发生在33%、33%和24.2%的患者中。根据PSA水平升高及其他临床标准，中位疾病进展时间为22.5周。估计中位总生存时间为69周。
EMP与96小时紫杉醇联合方案对HRPC患者具有活性。这些结果进一步支持了通过互补机制联合使用损害微管功能药物的治疗策略。
