Oregon Health and Science University, Portland, Oregon 97239-3098, USA.
Oncologist. 2013 Jun;18(6):687-8. doi: 10.1634/theoncologist.2011-0234. Epub 2013 Jun 5.
Prostate cancer (PC) is the most commonly diagnosed noncutaneous malignancy in American men. PC, which exhibits a slow growth rate and multiple potential target epitopes, is an ideal candidate for immunotherapy. GVAX for prostate cancer is a cellular immunotherapy, composed of PC-3 cells (CG1940) and LNCaP cells (CG8711). Each of the components is a prostate adenocarcinoma cell line that has been genetically modified to secrete granulocyte-macrophage colony-stimulating factor. Hypothesizing that GVAX for prostate cancer could be effective in a neoadjuvant setting in patients with locally advanced disease, we initiated a phase II trial of neoadjuvant docetaxel and GVAX. For the trial, the clinical effects of GVAX were assessed in patients undergoing radical prostatectomy (RP).
Patients received docetaxel administered at a dose of 75 mg/m(2) every 3 weeks for 4 cycles. GVAX was administered 2-3 days after chemotherapy preoperatively for four courses of immunotherapy. The first dose of GVAX was a prime immunotherapy of 5×10(8) cells. The subsequent boost immunotherapies consisted of 3×10(8) cells. After RP, patients received an additional six courses of immunotherapy. Pathologic complete response, toxicity, and clinical response were assessed. The primary endpoint of the trial was a pathologic state of pT0, which is defined as no evidence of cancer in the prostate.
Six patients completed neoadjuvant docetaxel and GVAX therapy. No serious drug-related adverse events were observed. Median change in prostate-specific antigen (PSA) following neoadjuvant therapy was 1.47 ng/ml. One patient did not undergo RP due to the discovery of positive lymph nodes during exploration. Of the five patients completing RP, four had a downstaging of their Gleason score. Undetectable PSA was achieved in three patients at 2 months after RP and in two patients at 3 years after RP.
Neoadjuvant docetaxel/GVAX is safe and well tolerated in patients with high-risk locally advanced PC. No evidence of increased intraoperative hemorrhage or increased length of hospital stay postoperatively was noted. These results justify further study of neoadjuvant immunotherapy.
前列腺癌（PC）是美国男性中最常见的非皮肤恶性肿瘤。PC 生长缓慢，具有多个潜在的靶标表位，是免疫治疗的理想候选者。前列腺癌 GVAX 是一种细胞免疫疗法，由 PC-3 细胞（CG1940）和 LNCaP 细胞（CG8711）组成。每个成分都是经过基因修饰以分泌粒细胞-巨噬细胞集落刺激因子的前列腺腺癌细胞系。假设前列腺癌 GVAX 在局部晚期疾病患者的新辅助治疗中可能有效，我们启动了新辅助多西他赛和 GVAX 的 II 期试验。在该试验中，通过接受根治性前列腺切除术（RP）的患者评估 GVAX 的临床效果。
患者每 3 周接受 75mg/m2 的多西他赛治疗 4 个周期。化疗后 2-3 天进行 4 个疗程的术前 GVAX 免疫治疗。GVAX 的第一个剂量为 5×108 个细胞的初始免疫治疗。随后的增强免疫治疗包括 3×108 个细胞。RP 后，患者接受了另外六轮免疫治疗。评估病理完全缓解、毒性和临床反应。该试验的主要终点是 pT0 的病理状态，定义为前列腺中无癌症证据。
六名患者完成了新辅助多西他赛和 GVAX 治疗。未观察到严重的药物相关不良反应。新辅助治疗后前列腺特异性抗原（PSA）的中位数变化为 1.47ng/ml。由于在探查期间发现淋巴结阳性，一名患者未进行 RP。在完成 RP 的五名患者中，有四名 Gleason 评分降级。三名患者在 RP 后 2 个月和两名患者在 RP 后 3 年实现了 PSA 无法检测。
高危局部晚期 PC 患者新辅助多西他赛/GVAX 安全且耐受良好。未观察到术中出血增加或术后住院时间延长。这些结果证明新辅助免疫治疗是合理的。
