A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: Safety assessment based on the phase I data
A phase I/II trial of a WT1 (Wilms' tumor gene) peptide vaccine in patients with solid malignancy: Safety assessment based on the phase I data
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DOI：
10.1093/jjco/hyl005
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发表时间：
2006-04-01
影响因子：
2.4
通讯作者：
Sakamoto, Junichi
中科院分区：
文献类型：
--
作者：
Morita, Satoshi;Oka, Yoshihiro;Sakamoto, Junichi
目的：我们进行了一项I期研究，以探讨每周WT 1肿瘤疫苗治疗的安全性与实体瘤患者，已难治所有其他anti-cancer therapy.Methods：皮试阴性患者皮内注射每周3.0毫克的HLA-A（*）2402限制性修改9聚体WT 1肽乳化在Montanide ISA 51佐剂。我们估计了每周接种WT 1疫苗时发生3级或4级毒性的贝叶斯后验概率。该分析为决定终止I期研究并转入II期研究提供了依据。此外，我们进行了探索性的评估WT 1 treatment.Results的抗肿瘤效果：10例患者接受了114疫苗接种WT 1每周一次。未观察到3级或4级毒性。基于贝叶斯方法，3级或4级毒性的概率极有可能低于20%（后验概率= 0.914）。观察到15例2级和2例1级毒性;然而，独立数据和安全性监测委员会确定所有这些事件与WT 1治疗无关。一名患者表现出部分反应，另外五名患者病情稳定，而每周接受WT 1 treatment.Conclusion：本文证实，每周WT 1疫苗接种的治疗方案的潜在毒性是可以接受的，并提出了潜在的抗肿瘤作用。因此，我们确认了继续进行II期试验的决定。
Objective: We conducted a phase I study to investigate the safety of a weekly WT1 tumor vaccine therapy in patients with solid tumors that had been refractory to all other anti-cancer therapies.Methods: Skin-test-negative patients were intradermally injected weekly for 12 weeks with 3.0 mg of an HLA-A(*)2402-restricted modified 9-mer WT1 peptide emulsified in Montanide ISA51 adjuvant. We estimated the Bayesian posterior probability of the occurrence of grade 3 or 4 toxicity when receiving the weekly WT1 vaccination. This analysis provided the basis for making a decision to terminate the phase I study and switch to phase II. Moreover, we performed an exploratory assessment of the anti-tumor effects of WT1 treatment.Results: Ten patients received 114 vaccinations with WT1 on a weekly schedule. No grade 3 or 4 toxicities were observed. Based on the Bayesian approach, it was highly likely that the probability of grade 3 or 4 toxicity was below 20% (the posterior probability = 0.914). Fifteen grade 2 and two grade 1 toxicities were observed; all of these incidents, however, were determined by the Independent Data and Safety Monitoring Committee to be unrelated to the WT1 treatment. One patient exhibited a partial response; five additional patients had stable disease while receiving weekly WT1 treatment.Conclusion: This paper confirms that the potential toxicities of the treatment schedule of weekly WT1 vaccination are acceptable and suggested a potential anti-tumor effect. Consequently, we validated the decision to continue to the phase II trial.