Japanese Journal of Clinical Oncology Advance Access published online on April 12, 2006
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyl005
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1 Department of Epidemiology and Health Care Research, Kyoto University Graduate School of Medicine, Kyoto, Japan
* To whom correspondence should be addressed. 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.
Received September 7, 2005
Accepted January 5, 2006
Original Article
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
Satoshi Morita 1 *,
Yoshihiro Oka 2,
Akihiro Tsuboi 3,
Manabu Kawakami 3,
Motohiko Maruno 4,
Shuichi Izumoto 4,
Tadashi Osaki 2,
Tetsuya Taguchi 5,
Takafumi Ueda 6,
Akira Myoui 6,
Sumiyuki Nishida 3,
Toshiaki Shirakata 2,
Satoshi Ohno 7,
Yusuke Oji 7,
Katsuyuki Aozasa 8,
Jun Hatazawa 9,
Keiko Udaka 10,
Hideki Yoshikawa 6,
Toshiki Yoshimine 4,
Shinzaburo Noguchi 5,
Ichiro Kawase 2,
Shin-ichi Nakatsuka 11,
Haruo Sugiyama 7,
and
Junichi Sakamoto 12
2 Department of Molecular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
3 Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
4 Department of Neurosurgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
5 Department of Surgical Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
6 Department of Orthopaedics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
7 Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
8 Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
9 Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
10 Department of Immunology, Kochi Medical School, Nankoku, Kochi, Japan
11 Department of Laboratory Medicine, National Hospital Organization, Osaka Minami Medical Center, Kawachinagano, Osaka, Japan
12 Department of Epidemiological & Clinical Research Information Management, Kyoto University Graduate School of Medicine, Kyoto, Japan
Satoshi Morita, E-mail: satoshi_morita{at}pbh.med.kyoto-u.ac.jp
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