A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma

Radiation Oncology

Koji Tsuboi¹  Tadao Ohno³  Atsuo Ito⁵  Yu Sogo⁵  Gerelchuluun Ariungerel¹  Junko Zenkoh¹  Hideyuki Sakurai¹  Takeji Sakae¹  Masashi Mizumoto¹  Haruko Numajiri¹  Ayae Kanemoto¹  Ichinosuke Hyodo²  Kazunori Ishige²  Masahiro Araki⁴  Takayuki Hashimoto¹  Kuniaki Fukuda²  Toshiyuki Okumura¹  Masato Abei² 

[1] Proton Medical Research Center, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennohdai, Tsukuba, Ibaraki 305-8575, Japan;Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennohdai, Tsukuba, Ibaraki 305-8575, Japan;Faculty of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo, and Cell-Medicine, Inc, 2-1-6-C-B-1 Sengen, Tsukuba, Ibaraki 305-0047, Japan;Department of Gastroenterology, Ibaraki Prefectural Central Hospital, 6528 Koibuchi, Kasama, Ibaraki 309-1793, Japan;Human Technology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan

关键词: Immunoadjuvant;    Immunotherapy;    Hepatocellular carcinoma;    Proton-beam radiotherapy;   

Others  :  1152784
DOI  :  10.1186/1748-717X-8-239

 received in 2013-03-25, accepted in 2013-10-05,  发布年份 2013

【 摘 要 】

Background

Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of ‘in situ’ tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC.

Methods

Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety.

Results

Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year.

Conclusions

Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted.

【 授权许可】

   
2013 Abei et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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