Kibel Adam S, Rosenbaum Eli, Kattan Michael W, Picus Joel, Dreicer Robert, Klein Eric A, Chatta Gurkamal S, Nelson Joel B, DiPaola Robert S, Roth Bruce J, Cookson Michael S, Wilding George, Jarrard David F, Beer Tomasz M, Ryan Christopher W, Petrylak Daniel P, Benson Mitchell C, Partin Alan W, Garrett-Mayer Elizabeth, Eisenberger Mario A
Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri 63105, USA.
J Urol. 2007 May;177(5):1777-81. doi: 10.1016/j.juro.2007.01.028.
Patients with adverse pathological features are at high risk for recurrence following radical prostatectomy. To improve outcomes in this population we performed a phase II study of adjuvant docetaxel in these high risk patients.
Patients with nonmetastatic radical prostatectomy at greater than 50% risk for recurrence by 3 years were eligible. Pathological findings were centrally reviewed and risk assessment was based on a validated multivariate Cox proportional hazards model. Treatment consisted of 6 cycles of 35 mg/m(2) docetaxel weekly given 4 to 12 weeks following surgery. Progression was defined as a prostate specific antigen of 0.4 ng/ml or greater, radiological/pathological evidence of recurrent disease or death from any cause. To screen for the potential benefit of adjuvant weekly docetaxel we used nomogram predicted progression-free survival as a historical control.
A total of 77 patients were registered between April 2002 and January 2004. Two patients had grade IV hyperglycemia and 20 had grade III toxicity. At a median followup of 29.2 months (range 1.6 to 39.2) 46 of 76 evaluable cases (60.5%) progressed. Observed median progression-free survival was 15.7 months (95% CI 12.8-25.1). Predicted median progression-free survival in a matched population was 10 months. Seven patients died, including 4 of prostate cancer, 1 with intra-abdominal bleeding during treatment and 2 of pneumonia and sudden cardiac death, respectively, following treatment.
Adjuvant docetaxel for prostate cancer is feasible with significant reversible but acceptable toxicity. The actual median progression-free survival of 15.7 months was longer than the nomogram predicted rate for this patient population. Adjuvant docetaxel treatment should be further evaluated in phase III trials in patients with high risk prostate cancer.
具有不良病理特征的患者在根治性前列腺切除术后复发风险较高。为改善该人群的治疗效果，我们对这些高危患者进行了一项多西他赛辅助治疗的II期研究。
符合条件的患者为非转移性根治性前列腺切除术患者，3年内复发风险大于50%。病理结果由中心审查，风险评估基于经过验证的多变量Cox比例风险模型。治疗包括在术后4至12周每周给予6个周期的35mg/m²多西他赛。疾病进展定义为前列腺特异性抗原达到0.4ng/ml或更高、复发性疾病的放射学/病理学证据或任何原因导致的死亡。为筛查辅助性每周多西他赛的潜在益处，我们使用列线图预测的无进展生存期作为历史对照。
2002年4月至2004年1月期间共登记了77例患者。2例患者出现IV级高血糖，20例出现III级毒性。在中位随访29.2个月（范围1.6至39.2个月）时，76例可评估病例中有46例（60.5%）出现疾病进展。观察到的中位无进展生存期为15.7个月（95%置信区间12.8 - 25.1）。匹配人群中预测的中位无进展生存期为10个月。7例患者死亡，其中4例死于前列腺癌，1例在治疗期间死于腹腔内出血，2例分别在治疗后死于肺炎和心源性猝死。
前列腺癌辅助性多西他赛治疗可行，毒性具有显著的可逆性但可接受。实际中位无进展生存期为15.7个月，长于该患者人群列线图预测的发生率。高危前列腺癌患者的辅助性多西他赛治疗应在III期试验中进一步评估。
