Department of Surgery, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Int J Oncol. 2012 May;40(5):1492-500. doi: 10.3892/ijo.2012.1351. Epub 2012 Feb 1.
Since the prognosis of non-small cell lung cancer (NSCLC) remains poor, the development of novel therapeutic approaches, including cancer vaccines, is highly desirable. In the current study, we conducted a phase II study of personalized peptide vaccination (PPV), in which a maximum of 4 peptides were selected based on pre-existing humoral immune responses and administered subcutaneously (weekly for 6 consecutive weeks and bi-weekly thereafter) in refractory NSCLC patients. Forty-one refractory NSCLC patients (4 stage IIIb, 22 stage IV and 15 recurrent), who had failed to respond to chemotherapy and/or targeted therapy (median number of regimens, 3; median duration, 10 months), were enrolled. Median overall survival (OS) was 304 days with a one-year survival rate of 42% in the enrolled patients. The main toxicity of PPV was skin reactions at the injection sites, but no serious adverse events were observed. In order to identify potential biomarkers for predicting OS, pre-vaccination and post-vaccination clinical findings and laboratory data were retrospectively assessed and evaluated by multivariate Cox regression analysis. Among the pre-vaccination factors examined, high C-reactive protein (CRP) level was a significant predictor of unfavorable OS [hazard ratio (HR)=10.115, 95% confidence interval (CI)=2.447-41.806, P=0.001]. Among the post-vaccination factors, high CRP level and low frequency of CD3⁺CD26⁺ cells were significant predictors of unfavorable OS (HR=23.127, 95% CI=2.919-183.233, P=0.003; HR=0.952, 95% CI=0.917-0.989, P=0.012). Taken together, our results suggest the feasibility of PPV for the treatment of refractory NSCLC. Evaluation of the identified factors before or at an early stage of vaccination could be potentially useful for selecting NSCLC patients who would likely have better prognosis following PPV.
由于非小细胞肺癌（NSCLC）的预后仍然较差，因此非常需要开发新的治疗方法，包括癌症疫苗。在目前的研究中，我们进行了一项个性化肽疫苗（PPV）的 II 期研究，该研究根据预先存在的体液免疫反应选择了最多 4 种肽，并通过皮下给药（连续 6 周每周一次，此后每两周一次）来治疗难治性 NSCLC 患者。纳入了 41 例难治性 NSCLC 患者（3 例 IIIb 期，22 例 IV 期和 15 例复发），这些患者对化疗和/或靶向治疗无反应（中位治疗方案数为 3，中位持续时间为 10 个月）。入组患者的中位总生存期（OS）为 304 天，一年生存率为 42％。PPV 的主要毒性是注射部位的皮肤反应，但未观察到严重的不良事件。为了确定预测 OS 的潜在生物标志物，我们通过多变量 Cox 回归分析回顾性评估和评估了接种前和接种后的临床发现和实验室数据。在检查的接种前因素中，高 C 反应蛋白（CRP）水平是 OS 不良的重要预测指标[风险比（HR）=10.115，95％置信区间（CI）=2.447-41.806，P=0.001]。在接种后的因素中，高 CRP 水平和 CD3⁺CD26⁺细胞频率低是 OS 不良的重要预测指标（HR=23.127，95％CI=2.919-183.233，P=0.003；HR=0.952，95％CI=0.917-0.989，P=0.012）。综上所述，我们的结果表明 PPV 治疗难治性 NSCLC 的可行性。在接种前或早期评估鉴定的因素可能对选择接受 PPV 治疗后预后更好的 NSCLC 患者具有潜在的应用价值。
