Noguchi Masanori, Mine Takashi, Yamada Akira, Obata Yayoi, Yoshida Kazumi, Mizoguchi Junko, Harada Mamoru, Suekane Shigetaka, Itoh Kyogo, Matsuoka Kei
Department of Urology, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Oncol Res. 2007;16(7):341-9. doi: 10.3727/000000006783980955.
The aim of this study was to investigate prognostic factors of patients with metastatic hormone refractory prostate cancer (HRPC) under combined administration of personalized peptide vaccination and low-dose estramustine phosphate (EMP). From February 2001 to July 2004, 58 men with metastatic HRPC received the combination therapy of personalized peptide vaccination and low-dose EMP. Conducted immune monitorings for those patients were peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay. Clinical responses and survival times were also evaluated. The combination therapy was well tolerated with no major adverse effects. Increased levels of CTL precursors and IgG responses to the vaccinated peptides were observed in 29 of 37 (78%) patients and in 36 of 41 (88%) patients tested, respectively. A prostate-specific antigen decline of at least 50% occurred in 24% of patients. The median survival time was 17 months (95% confidence interval, 12-25 months). Cox proportional hazards analysis showed that a low number of lymphocytes (p = 0.0075, odds ratio 2.700), a negative immunological activity response after the vaccination (p = 0.0185, odds ratio 2.658), and poor performance status (p = 0.0347, odds ratio 2.569) were independent predictors of disease death. These encouraging results show the need for further evaluation of the combination of personalized peptide vaccination and low dose of EMP for metastatic HRPC patients.
本研究的目的是调查接受个性化肽疫苗接种与低剂量磷酸雌莫司汀（EMP）联合治疗的转移性激素难治性前列腺癌（HRPC）患者的预后因素。2001年2月至2004年7月，58例转移性HRPC男性患者接受了个性化肽疫苗接种与低剂量EMP的联合治疗。对这些患者进行的免疫监测包括通过干扰素-γ产生进行肽特异性细胞毒性T淋巴细胞（CTL）前体分析，以及通过酶联免疫吸附测定进行肽反应性免疫球蛋白G（IgG）检测。还评估了临床反应和生存时间。联合治疗耐受性良好，无重大不良反应。在37例接受检测的患者中有29例（78%）观察到CTL前体水平升高，在41例接受检测患者中有36例（88%）观察到对接种肽的IgG反应增强。24%的患者前列腺特异性抗原下降至少50%。中位生存时间为17个月（95%置信区间，为12 - 25个月）。Cox比例风险分析表明，淋巴细胞数量少（p = 0.0075，比值比2.700）、接种疫苗后免疫活性反应为阴性（p = 0.0185，比值比2.658）以及体能状态差（p = 0.0347，比值比2.569）是疾病死亡的独立预测因素。这些令人鼓舞的结果表明，需要对转移性HRPC患者的个性化肽疫苗接种与低剂量EMP联合治疗进行进一步评估。
