Evaluation of Dose Escalation Scheme in Oncologic Phase I Gene Therapy and Development of New Dose Escalation Scheme.
| Project/Area Number |
13671049
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGAMURA Fumitaka The University of Tokyo, The Institute of Medical Science, Research Associate, 医科学研究所, 助手 (90282491)
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| Co-Investigator(Kenkyū-buntansha) |
TANI Kenzaburo Kyushu University, Medical Institute of Bioregulation, Professor, 生体防御医学研究所, 教授 (00183864)
TOJO Arinobu The University of Tokyo, The Institute of Medical Science, Associate Professor, 医科学研究所, 助教授 (00211681)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Gene Therapy / Oncologic Disease / Dose Escalation Scheme |
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| Research Abstract |
We evaluated the results of Oncology Phase I gene therapy which used dose escalation scheme as the followings : I) The incidence of intratumoral injection was 42.6% and that of subcutaneous was 10.6%. On the contrary, the incidence of systemic administration was low. Those of intravenous and imtramuscular were 4.3% and 4.3%, respectively ; II) Forty-five studies enrolled the same number of patients on each dose levels. Three patient cohorts was used in 75.6% of studies. One or two patient cohorts were used in one study ; III) The median numbe of dose levels was 4, and the range was 2-12 levels ; IV) About half the studies used 1 log or half-log dose increments. Seventeen percent of studied increased their dose for 1 log for a while, and then changed to half-log. The maximum dose increment was 2-log ; V) Four studies (8.2%) displayed Dose Limiting Toxicities, none of studies was based on the Immunotherapy. Only the three studies (6.3%) could determine Maximum Tolerated Dose.
Based on the above findings, we tried to develop a novel dose escalation scheme using pharmacologically-guided model, mathematical model, toxicity-based model. Finally, we developed a novel dose escalation model based on toxicity. The model is : available when the concept of gene therapy is based on immunotherapy ; Local adminstration, such as intratumoral and subcutaneous ; dose increment is 2-log until the occurrence of any injection site grade 【greater than or equal】 2 (NCI CTC ver.2) adverse events. Thereafter, dose increment is 1-log. When we applied this model to the past studies, it is estimated that one or two dose level can be eliminated and reached Maximum Administered Dose with sufficient safety. We plan to apply this model prospectively for the future gene therapy to evaluate the exact benefit of this model.
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Report
(3 results)
Research Products
(15 results)
