A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer
A randomized phase II trial of personalized peptide vaccine plus low dose estramustine phosphate (EMP) versus standard dose EMP in patients with castration resistant prostate cancer
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DOI：
10.1007/s00262-010-0822-4
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发表时间：
2010-07-01
影响因子：
5.8
通讯作者：
Itoh, Kyogo
中科院分区：
文献类型：
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作者：
Noguchi, Masanori;Kakuma, Tatsuyuki;Itoh, Kyogo
个性化肽疫苗接种（PPV）联合化疗可能是许多癌症患者的新方法。在这项随机研究中，我们评价了PPV联合低剂量磷酸雌莫司汀（EMP）与标准剂量EMP相比在HLA-A2或A24阳性去势抵抗性前列腺癌患者中的抗肿瘤作用和安全性。患者被随机分为接受PPV加低剂量EMP（280 mg/天）或标准剂量EMP（560 mg/天）的组。疾病进展后，患者转为相反方案。主要终点是无进展生存期（PFS）。我们随机分配28例患者接受PPV加低剂量EMP，29例患者接受标准剂量EMP。PPV组和EMP组分别有19起和20起事件发生在首次治疗期间。PPV组首次治疗的中位PFS为8.5个月，EMP组为2.8个月，风险比（HR）为0.28（95% CI，0.14-0.61;对数秩P = 0.0012），而第二次治疗的中位PFS无差异。总生存期的HR为0.3（95% CI，0.1-0.91），PPV+低剂量EMP组更有利（对数秩，P = 0.0328）。PPV加低剂量EMP耐受性良好，无重大不良反应，IgG和细胞毒性T细胞对接种肽的应答水平增加。与标准剂量EMP单药相比，PPV+低剂量EMP与基于PSA的PFS改善相关。
Personalized peptide vaccination (PPV) combined with chemotherapy could be a novel approach for many cancer patients. In this randomized study, we evaluated the anti-tumor effect and safety of PPV plus low-dose estramustine phosphate (EMP) as compared to standard-dose EMP for HLA-A2- or -A24-positive patients with castration resistant prostate cancer. Patients were randomized into groups receiving either PPV plus low-dose EMP (280 mg/day) or standard-dose EMP (560 mg/day). After disease progression, patients were switched to the opposite regime. The primary end point was progression-free survival (PFS). We randomly assigned 28 patients to receive PPV plus low-dose EMP and 29 patients to receive standard-dose EMP. Nineteen events in the PPV group and 20 events in the EMP group occurred during the first treatment. Median PFS for the first treatment was 8.5 months in the PPV group and 2.8 months in the EMP group with a hazard ratio (HR) of 0.28 (95% CI, 0.14-0.61; log-rank P = 0.0012), while there was no difference for median PFS for the second treatment. The HR for overall survival was 0.3 (95% CI, 0.1-0.91) in favor of the PPV plus low-dose EMP group (log-rank, P = 0.0328). The PPV plus low-dose EMP was well tolerated without major adverse effects and with increased levels of IgG and cytotoxic-T cell responses to the vaccinated peptides. PPV plus low-dose EMP was associated with an improvement in PSA-based PFS as compared to the standard-dose EMP alone.