McKay Rana R, Gray Kathryn P, Hayes Julia H, Bubley Glenn J, Rosenberg Jonathan E, Hussain Arif, Kantoff Philip W, Taplin Mary-Ellen
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Genitourinary Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Cancer. 2015 Aug 1;121(15):2603-11. doi: 10.1002/cncr.29398. Epub 2015 Apr 22.
Patients with biochemical disease recurrence (BCR) after definitive treatment for prostate cancer comprise a heterogeneous population for whom standard therapy options are lacking. The purpose of the current trial was to evaluate the feasibility, toxicity, and efficacy of early multimodality systemic therapy in men with BCR.
Eligible patients had an increasing prostate-specific antigen (PSA) level, a PSA doubling time ≤10 months, and no evidence of metastases after radical prostatectomy (RP) and/or radiotherapy (RT) for localized disease. Treatment consisted of docetaxel at a dose of 75 mg/m(2) every 3 weeks for 4 cycles, bevacizumab at a dose of 15 mg/kg every 3 weeks for 8 cycles, and androgen deprivation therapy (ADT) for 18 months. The primary endpoint was the percentage of patients who were free from PSA progression 1 year after the completion of therapy.
A total of 41 patients were included in the analysis. At 1 year after the completion of ADT, 45% of patients (13 of 29 patients) and 29% of patients (5 of 17 patients) with a testosterone level ≥100 ng/dL and ≥240 ng/dL, respectively, had a PSA <0.2 ng/mL. The median follow-up was 27.5 months (interquartile range, 21.8-38.1 months). Eight patients (20%) were free from PSA progression, 19 patients (46%) did not reinitiate ADT, and 34 patients (83%) were free from metastasis. Sixteen patients (39%) experienced grade 3 and 5 patients (12%) experienced grade 4 toxicities (toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]).
Multimodality systemic therapy with docetaxel, bevacizumab, and ADT is feasible and produces PSA responses in men with BCR. Long-term follow-up is needed to determine the percentage of patients with a durable PSA response who are able to avoid having to reinitiate prostate cancer therapy.
前列腺癌确定性治疗后出现生化复发（BCR）的患者构成了一个异质性群体，目前缺乏针对他们的标准治疗方案。本试验的目的是评估早期多模式全身治疗对BCR男性患者的可行性、毒性和疗效。
符合条件的患者前列腺特异性抗原（PSA）水平升高，PSA倍增时间≤10个月，且在接受局限性疾病的根治性前列腺切除术（RP）和/或放射治疗（RT）后无转移证据。治疗方案包括每3周一次剂量为75mg/m²的多西他赛，共4个周期；每3周一次剂量为15mg/kg的贝伐单抗，共8个周期；以及18个月的雄激素剥夺治疗（ADT）。主要终点是治疗完成1年后无PSA进展的患者百分比。
共有41例患者纳入分析。在ADT完成1年后，睾酮水平≥100ng/dL和≥240ng/dL的患者中，分别有45%（29例中的13例）和29%（17例中的5例）的PSA<0.2ng/mL。中位随访时间为27.5个月（四分位间距，21.8 - 38.1个月）。8例患者（20%）无PSA进展，19例患者（46%）未重新开始ADT，34例患者（83%）无转移。16例患者（39%）出现3级毒性，5例患者（12%）出现4级毒性（毒性采用美国国立癌症研究所不良事件通用术语标准[3.0版]进行评估）。
多西他赛、贝伐单抗和ADT的多模式全身治疗对BCR男性患者是可行的，并能产生PSA反应。需要长期随访以确定能够避免重新开始前列腺癌治疗的具有持久PSA反应的患者百分比。
