Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence - From US Military Cancer Institute clinical trials group study I-01 and I-02
Optimal dose and schedule of an HER-2/neu (E75) peptide vaccine to prevent breast cancer recurrence - From US Military Cancer Institute clinical trials group study I-01 and I-02
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DOI：
10.1002/cncr.23772
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发表时间：
2008-10-01
期刊：
影响因子：
6.2
通讯作者：
Peoples, George E.
中科院分区：
文献类型：
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作者：
Holmes, Jarrod P.;Gates, Jeremy D.;Peoples, George E.
背景E75是一种HER-2/neu衍生肽，在无疾病淋巴结阳性（NP）和淋巴结阴性（NN）乳腺癌（BCa）患者中作为预防性疫苗与粒细胞-巨噬细胞集落刺激因子（GM-CSF）一起给药。最佳生物剂量（OBD）的基础上确定的毒性和免疫反应。患者在6个月内（3、4或6次）接种不同剂量的E75加GM-CSF。根据国家癌症研究所通用术语标准对毒性进行分级。通过迟发型超敏反应试验（DTH）测定免疫应答，并通过人白细胞抗原-A2：免疫球蛋白G diner和流式细胞术定量E75特异性CD 8（+）T细胞。99名患者（48名NP和51名NN）在7个剂量组中接种疫苗。OBD为每月1000 μ g E75加250 μ g GM-CSF × 6。最佳剂量组（ODG，n = 29）的毒性与次佳剂量组（SDG，n = 70）相似，次佳剂量组由其余6组组成。ODG显示出平均疫苗后二聚体增加的趋势（0.87 +/- 0.10% vs 0.67 +/- 0.05%; P = 0.07），DTH反应显著更大（21.5 +/- 2.5 mm vs 11.3 +/- 1.3 mm; P = 0.0002），以及复发率降低的趋势（3.4% vs 12.9%; P = 0.27）。与SDG相比，ODG的肿瘤更大（≥ T2的百分比：55% vs 23%; P = 0.004），阳性淋巴结更多（NP百分比：76% vs 37%; P = 0.001），肿瘤分级更高（3级百分比：52% vs 30%; P = 0.07），但中位随访时间更短（20个月vs 32个月; P
BACKGROUND. E75, a HER-2/neu-derived peptide, was administered as a preventive vaccine with graulocyte-macrophage-colony-stimulating factor (GM-CSF) in disease-free lymph node-positive (NP) and lymph node-negative (NN) breast cancer (BCa) patients. The optimal biologic dose (OBD) was determined based on toxicity and immunologic response.METHODS. Patients were vaccinated over 6 months (3, 4, or 6 times) with different doses of E75 plus GM-CSF. Toxicities were graded per National Cancer Institute Common Terminology Criteria. GM-CSF vas reduced for significant toxicity Immunologic response was measured by delayed type hypersensitivity test (DTH), and E75-specific CD8(+) T-cells were quantified with human leukocyte antigen-A2:immunoglobulin G diner and flow cytometry.RESULTS. Ninety-nine patients (48 NP and 51 NN) were vaccinated in 7 dose groups. The OBD was 1000 mu g E75 plus 250 mu g GM-CSF monthly x 6. The optimal dose group (ODG, n = 29) experienced similar toxicities to the suboptimal dose group (SDG, n = 70), which was comprised of the remaining 6 groups. The ODG demonstrated a trend toward an increase in the average postvaccine dimer (0.87 +/- 0.10% vs 0.67 +/- 0.05%; P =.07), a significantly larger DTH response (21.5 +/- 2.5 mm vs 11.3 +/- 1.3 mm; P =.0002), and a trend toward decreased recurrences (3.4% vs 12.9%; P =.27). Compared with the SDG, the ODG had larger tumors (percentage >= T2: 55% vs 23%; P =.004), more positive nodes (percentage NP: 76% vs 37%; P =.001), and higher grade tumors (percentage grade 3: 52% vs 30%; P =.07), but a shorter median follow-up time (20 months vs 32 months; P