Morita Satoshi, Oka Yoshihiro, Tsuboi Akihiro, Kawakami Manabu, Maruno Motohiko, Izumoto Shuichi, Osaki Tadashi, Taguchi Tetsuya, Ueda Takafumi, Myoui Akira, Nishida Sumiyuki, Shirakata Toshiaki, Ohno Satoshi, Oji Yusuke, Aozasa Katsuyuki, Hatazawa Jun, Udaka Keiko, Yoshikawa Hideki, Yoshimine Toshiki, Noguchi Shinzaburo, Kawase Ichiro, Nakatsuka Shin-ichi, Sugiyama Haruo, Sakamoto Junichi
Department of Epidemiology and Health care Research, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Jpn J Clin Oncol. 2006 Apr;36(4):231-6. doi: 10.1093/jjco/hyl005. Epub 2006 Apr 12.
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.
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.
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.
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.
我们开展了一项I期研究，以调查每周一次的WT1肿瘤疫苗疗法对所有其他抗癌疗法均难治的实体瘤患者的安全性。
皮肤试验阴性的患者每周皮内注射一次3.0毫克HLA-A*2402限制性修饰9肽WT1，共注射12周，该肽乳化于Montanide ISA51佐剂中。我们估计了接受每周一次WT1疫苗接种时发生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，我们对WT1治疗的抗肿瘤效果进行了探索性评估。
10名患者按每周一次的计划接受了114次WT1疫苗接种。未观察到3级或4级毒性。基于贝叶斯方法，3级或4级毒性的概率很可能低于20%（后验概率=0.914）。观察到15例2级毒性和2例1级毒性；然而，独立数据与安全监测委员会确定所有这些事件均与WT1治疗无关。1例患者出现部分缓解；另外5例患者在接受每周一次WT1治疗时病情稳定。
本文证实每周一次WT1疫苗接种治疗方案的潜在毒性是可接受的，并提示了潜在的抗肿瘤作用。因此，我们验证了继续进行II期试验的决定。
