Browse > Article

Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products  

Namgung, Mi-Ae (College of Oriental Mediicine, Kyunghee University)
Chang, Yoo-Sung (College of Oriental Mediicine, Kyunghee University)
Jeong, Seung-Gi (College of Oriental Mediicine, Kyunghee University)
Kim, Jin-Seung (College of Oriental Mediicine, Kyunghee University)
Yoon, Sung-Woo (College of Oriental Mediicine, Kyunghee University)
Jang, Ki-Young (College of Oriental Mediicine, Daejeon University)
Yoo, Hwa-Seung (College of Oriental Mediicine, Daejeon University)
Jung, Myeon-Woo (Drug Metabolism Team, National Institute of Toxicological Research, KFDA)
Lee, Sung-Ho (Korea University Medical Center)
Kim, Sung-Hoon (College of Oriental Mediicine, Kyunghee University)
Publication Information
Journal of Physiology & Pathology in Korean Medicine / v.20, no.6, 2006 , pp. 1678-1727 More about this Journal
Abstract
This study was perfromed to develop the assessment guideline and endpoints for clinical trial with anticancer herbal medicine. The botanical products used to humans for long time may be applied to phase 3 clinical trial after submitting the evidences for safety and efficacy of them or completion of basic requirement of phase 1 and phase 2 for safety confirmation and dose determination. Syndrome improvement was chiefly evaluated by Zubrod and karnofsky(%) methods. We suggest the general clinical trial assessment with botanical products, by following assessment points, that is, tumor size for 50 points, survival fate for 10 points, major syndromes for 40 points. It is recommendable that the each symptom of Qi deficiency syndrome, blood deficiency syndrome and Qi stagnation syndrome was allocated by assessment points, Similarly, the each symptom was given the assessment points according to the severity of symptom, for example, slight for 3 points, moderate for 2 points and severe for 1 point in hepatocelluar carcinoma and lung cancer. Then, the efficacy of botanical products was evaluated by the difference between pre-treatment and post-treatment. Asking the neoplastic patients of questionnaire on physical, emotional, cognitive, social and role subjects availability, three more syndromes (Fatigue, Pain and Nausea/Vomit), quality of life(QOL) will be evaluated by GLM statistics. In addition, in case of lung cancer, 13 questions will be asked by the EORTC QLQ-C13 forms. As the assessment of endpoints for efficacy to reduce side effects induced by chemotherapy and radiotherapy, the data of image scanning and hemato-urinalysis can be usefully applied on immune response, weight loss, indigestion, hemopoietic damage and injury of liver and kidney, while the changes of syndromes of side effect can be evaluated by differentiation methods of Qi and blood and five viscera. However, it is still necessary to determine the ratio between scientific analytical method and Oriental differentiation method as well as confirm the Oriental assessment endpoints by clinical trial. In addition, we suggest the continuous development of assessment endpoints on other carcinomas except of hepatocelluar carcinoma and lung cancer in future.
Keywords
Clinical Trial; Endpoints; Antitumor Natural Products; QOL;
Citations & Related Records
연도 인용수 순위
  • Reference
1 중화인민공화국위생부, 중약신약임상연구지도원칙, 제2집, 1995
2 Food and Drug Administration, Guidance for industry: significant scientific agreement in the review of health claims for conventional foods and dietary supplements, USA, 1999
3 Anthony.J.Neal.ClinicalOncology3rdedition(basic principles and practice), Oxford University Press, 123-137, 2003
4 왕영염주편, 중의내과학, 상무인서관, 391-397, 2000
5 周雄順 外. 藥論惡性腫瘤 放化療後的中醫治療原則, 浙江中醫學院學報, 3:11-12, 1990
6 양유걸주편, 암증종류의론의화정선, 약군문화사업공사, 408- 415, 1989
7 浙江中醫學院學報編輯委員會, 腫留-中醫藥防治癌症病人放化療副反應, 浙江中醫學院學報, 6:49, 1986
8 WHO, QOL(quality of life) user manual : facet definitions and response scales, WHO, 601-671. 1998
9 蔡德政. 黨蔘花粉治療放療化療所致造血功能障碍26例療效初步觀察, 中醫雜誌 11:25-26, 1987
10 EORTC, Study on Quality of Life Version 3.0, EORTC, 1995
11 金光 外. 中藥防治腫瘤化療毒副反應509例臨床觀察, 陜西中醫, 11:485, 1990
12 Han, J.Y., Kim, H.K., Choi, B.G., Moon, H., Hong, Y.S., Lee, K.S. Quality of life (QOL) assessment of MIP (mitomycin, ifosfamide and cisplatin) chemotherapy in advanced non-small cell lung cancers (NSCLC). Jpn J Clin Oncol. 28(12):749-753. 1998   DOI   ScienceOn
13 徐悔文. 降逆湯防治腫瘤化療消化道反應三十七例, 浙江中醫雜誌, 1:5, 1989
14 양검유등. 현대종류학, 상해의과대학, pp 425-428, 1993
15 Center for Drug Evaluation and Research(CDER), Department of Health and Human Services Food and Drug Administration, Guidance for industry : botanical drug products, 2004
16 EMEA, Guideline On The Clinical Assessment Of Fixed Combinations Of Herbal Substances / Herbal Preparations, Doc.Ref.EMEA/HMPC/166323, 2005
17 Bishop, Fienberg & Holland. Discrete Multivariate Analysis, MIT Press, p 103, 1975
18 식품의약품안전청, 천연물신약연구개발촉진법 제 2조, 법률제6165호 신규제정 2000
19 Katsutoshi Terasawa, Kampo, tokyo, K.K. Standard Mcintyre, 22, 1993
20 이천림, 질변통계, 양유근 주편:위생통계학 제2판, 북경 인민위생출판사, 207-209, 1990
21 Wesley, M.N., Wesley, R.A. Biostatics in clincial trials In: Textbook of oncology., Williams and Wilkins, pp 346-348, 1986
22 식품의약품안전청. 임상시험의 전반적인 고려사항, 생물의약품평가자료집 13, 2004
23 Center for Drug Evaluation and Research(CDER) & Center for Biologics Evaluation and Research(CBER), Guidance for industry : clinical trial endpoints for the approval of cancer drugs and biologics, 2005
24 Rosner. Fundamentals of Biostatistics, 5th Edition, 39, 2000
25 대한의학협회 분과학회협의회 편저: 의학총서 암의 진단과 치료, 여문각, 23-35, 1992
26 Abrial, S.C., Penault-Llorca, F., Delva, R., Bougnoux, P., Leduc, B., Mouret-Reynier, M.A., Mery-Mignard, D., Bleuse, J.P., Dauplat, J., Cure, H., Chollet, P. High prognostic significance of residual disease after neoadjuvant chemotherapy: a retrospective study in 710 patients with operable breast cancer. Breast Cancer Res Treat. 3:1-9, 2005   DOI
27 Bertil Axelsson, Tryck & Medier. The incurable cancer patient at the end of life, Uppsala University, 2001
28 Vencent T DeVita. Cancer principle and practice of oncology 4th ed., JB LIPPINCOTT Company, 678-887, 1993
29 정수유. 중약신약임상연구 지도원칙 :시행(中藥新藥臨床硏究指導原則:試行), 중국의약기술출판사, 제024754호, 207-224, 2004
30 서울대 의과대학, 선경인더스트리 연구소: 제3세대 백금착제 항암제 신약개발 보고서, 보건복지부, 1994
31 National Cancer Institute(NCI), Cancer Clinical Trials: The Basic Workbook, National Institutes of Health(No.02-5050), 2001
32 Martin, D. Abeloff, Clinical oncology, Churchill Livingstone Inc. 1999
33 중화인민공화국위생부, 중약신약임상연구지도원칙, 제1집, 1993
34 중화인민공화국위생부, 중약신약임상연구지도원칙, 제3집, 1997
35 한국식품안전청 의약품안전국. 임상시험통계지침, 의약 65625-13553호, 2000
36 WHO/EDM/TRM, General guidelines for methodologies on research and evaluation of traditional medicine, 2000
37 鞠永棕編. 고오스 藥理學, 서울, 汎文社, 701-710, 1986
38 이용구, 통계학원론, 율곡출판사, 199-222, 1991