The Journal of Internal Korean Medicine (대한한방내과학회지)

The Society of Internal Korean Medicine (대한한방내과학회)
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Analysis of Existing Guidelines and Randomized, Controlled, Clinical Trials for Development of [Guideline of Clinical Trial on Herbal Medicinal Product for Liver Cancer]

간암 한약제제 임상시험 가이드라인 개발을 위한 한약제제 무작위배정 대조군 임상시험 고찰

  • Received : 2019.03.09
  • Accepted : 2019.03.28
  • Published : 2019.03.30
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Abstract

Objective: This study aimed to ascertain what should be considered in the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer," by analyzing existing guidelines and clinical trials. Methods: Committee for the development of a guideline, consisting of 6 Korean medicine doctors, reviewed guidelines and clinical trials on using herbal medicine for treating liver cancer. The trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparators, outcomes, and trial design. We then compared the results of our analysis with the guidelines to identify issues we must to consider when following the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer." Several guidelines for antitumor agents and clinical trials on herbal medicine were obtained from the Ministry of Food and Drug Safety homepage, etc. The search terms were as follows: "liver neoplasms"; "herbal medicine"; "medicine, Korean traditional"; and "medicine, Chinese Traditional.". Results: Ten articles were obtained from pubmed and Embase. There was no guideline for clinical trials on using herbal medicine for treating liver cancer. All the participants in the reviewed articles had primary liver cancer, and the type of intervention varied (e.g., decoction, patches, and capsules. The comparators included placebos and conventional treatments such as chemotherapy. The outcome assessment methods were tumor response, quality of life, survival, and liver function tests. Adverse events occuring during the trial were also evaluated. Conclusion: Findings were derived by reviewing existing guidelines and comparing them with clinical trials on liver cancer and herbal medicinal products. These results will be utilized in the development of the "Guideline for Clinical Trials with Herbal Medicinal Products for Liver Cancer."

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References

  1. Lee HS, Lee JH, Seo KS, Lim HY. Oncology. Revised edition. Park JG, Bang YJ, Ha SH, editors. Seoul: Iljogak; 2012, p. 339.
  2. Global Cancer Observatory[Internet]. Lyon, France: International Agency for Research on Cancer;[cited 2019 Feb 28]. Available from: http://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf
  3. Wallace MC, Preen D, Jeffery GP, Adams LA. The evolving epidemiology of hepatocellular carcinoma: a global perspective. Expert Rev Gastroenterol Hepatol2015 Jun;9(6):765-79. https://doi.org/10.1586/17474124.2015.1028363
  4. National Center Information Cancer [Internet]. Goyang-si, Republic of Korea: Ministry of Health and Welfare; [cited 2019 Feb 28]. Available from : https://www.cancer.go.kr
  5. Korean Statistical Information Service [Internet]. Daejeon Metropolitan City: Statistics Korea; [cited Feb 28]. Available from: http://kosis.kr/statHtml/statHtml.do?orgId=117&tblId=DT_117N_A00021&conn_path=I2
  6. Park JW. National project for Early screening of Liver cancer. Clin Mol Hepatol 2002;8(3):16-9.
  7. National Comprehensive Cancer Network [internet]. Plymouth Meeting, USA: National Comprehensive Cancer Network;[cited 2019 Feb 28]. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf
  8. Committee of Korean Clinical Practice Guideline for Hepatocellular carcinoma. Practice Guidelines for Management of Hepatocellular Carcinoma. Seoul: The Korean Liver Cancer Association and National Cancer Center, Korea; 2018.
  9. Minagawa M, Makuuchi M, Takayama T, Kokudo N. Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg 2003;238(5):703-10. https://doi.org/10.1097/01.sla.0000094549.11754.e6
  10. Park JW, Chen M, Colombo M, Roberts LR, Schwartz M, Chen PJ, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study. Liver Int 2015;35(9):2155-66. https://doi.org/10.1111/liv.12818
  11. Yoo SH, Bae SH. Complications Associated with Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma. Korean J of liver cancer study group2011;11(2):144-8.
  12. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst 2008;100(10):698-711. https://doi.org/10.1093/jnci/djn134
  13. Thomas MB. Systemic therapy for hepatocellular carcinoma. Cancer Journal 2008;14(2):123-7. https://doi.org/10.1097/PPO.0b013e31816a6058
  14. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359(4):378-90. https://doi.org/10.1056/NEJMoa0708857
  15. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol 2009;10(1):25-34. https://doi.org/10.1016/S1470-2045(08)70285-7
  16. Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, et al. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol 2013;31(32):4067-75. https://doi.org/10.1200/JCO.2012.45.8372
  17. Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, et al. Linifanib versus Sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015;33(2):172-9. https://doi.org/10.1200/JCO.2013.54.3298
  18. Bruix J, Raoul JL, Sherman M, Mazzaferro V, Bolondi L, Craxi A, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: subanalyses of a phase III trial. J Hepatol 2012;57(4):821-9. https://doi.org/10.1016/j.jhep.2012.06.014
  19. Raoul JL, Bruix J, Greten TF, Sherman M, Mazzaferro V, Hilgard P, et al. Relationship between baseline hepatic status and outcome, and effect of sorafenib on liver function: SHARP trial subanalyses. J Hepatol 2012;56(5):1080-8. https://doi.org/10.1016/j.jhep.2011.12.009
  20. Llovet JM, Pe CE, Lathia CD, Shan M, Meinhardt G, Bruix J, et al. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma. Clin Cancer Res 2012;18(8):2290-300. https://doi.org/10.1158/1078-0432.CCR-11-2175
  21. Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double blind, placebo-controlled, phase 3 trial. Lancet 2017;389(10064):56-66. https://doi.org/10.1016/S0140-6736(16)32453-9
  22. El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet 2017;389(10088):2492-502. https://doi.org/10.1016/S0140-6736(17)31046-2
  23. Kim BH, Park JW. Systemic Therapy for Advanced Hepatocellular Carcinoma: Targeted Therapy and Immunotherapy. J Liver Cancer 2018;18(1):17-22. https://doi.org/10.17998/jlc.18.1.17
  24. Michot JM, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, et al. Immunerelated adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 2016 Feb;54:139-48. https://doi.org/10.1016/j.ejca.2015.11.016
  25. Bourke JM, O'Sullivan M, Khattak MA. Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors). Med J Aust 2016 Nov 7;205(9):418-24. https://doi.org/10.5694/mja16.00586
  26. Wang S, Long S, Wu WY. Application of Traditional Chinese Medicines as personalized therapy in human cancers. Am J Chin Med 2018;46(5):953-70. https://doi.org/10.1142/S0192415X18500507
  27. Han GJ, Seong S, Kim SS, Kim JS, Park JW. Analysis of Existing Guidelines and Randomized, Controlled, Clinical Trials for Development of [Guideline of Clinical Trial with Herbal Medicinal Product for gastric cancer]. J Korean Med 2017;38(3):124-42. https://doi.org/10.13048/jkm.17031
  28. Ruan WJ, Lai MD, Zhou JG. Anticancer effects of Chinese herbal medicine, science or myth? J Zhejiang Univ Sci B2006;7(12):1006-14. https://doi.org/10.1631/jzus.2006.B1006
  29. Kim KS, Kim SH, Eo WK, Cheon SH, Eo SK, Jo HJ. Clinical research methodology for traditional Korean medicine treatment of lung cancer : Evidence based approach. J Oriental Medical Classics2010;23(4):39-62.
  30. Hong SH, Son HY. Clinical Practice Guidelines of Korean Medicine for Hepatocellular Carcinoma. J of Kor Traditional Oncology 2015;20(1):55-79. https://doi.org/10.15432/JKTO.2015.20.1.055
  31. Kim SH, Namgung MA, Chang YS, Jeong SK, Kim JS, Yoon SW, et al. Study on Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Products. J Physiol & Pathol Korean Med 2006;20(6):1678-727.
  32. Ministry of Food and Drug Safety. Guideline for evaluation of clinical trial of anticancer drugs.
  33. National Institute of Food and Drug Safety Evaluation. Guidelines for clinical testing of anti-cancer drugs and non-clinical test data for approval of items. 2010.11.
  34. National Institute of Food and Drug Safety Evaluation. Guidelines for clinical trial of anti-cancer drugs. 2015.12.
  35. National Institute of Food and Drug Safety Evaluation. Guidelines for non-clinical trial of anti-cancer drugs. 2015.12.
  36. National Institute of Food and Drug Safety Evaluation. Guidelines for Exemption of Anticancer Drug Data in Bridging Study. 2015.07.
  37. Ministry of Food and Drug Safety. Guideline for the use of clinical trial medicines for therapeutic purposes. 2018.04.
  38. Kim CM. Recommendations for Early Screening of Liver Cancer. Seoul: Korean Association for the Study of the Liver and National Cancer Center, Korea; 2001.
  39. Korean Institution of Oriental Medicine. A study on the clinical trial guidelines of herbal medicinal drug. Seoul: Ministry of Food and Drug Safety; 2005.01.
  40. Korean Institution of Oriental Medicine. A Study on the clinical trial guideline of herbal medical drug(II). Seoul: Ministry of Food and Drug Safety; 2005.11.
  41. Industry-Academia Collaboration Foundation, KyungHee University. Research on outcome indicators for clinical trials of herbal medicinal products. Seoul: Ministry of Food and Drug Safety; 2006.
  42. Ministry of Food and Drug Safety. General considerations in clinical trials of herbal medicine preparations. Seoul: Ministry of Food and Drug Safety; 2007.
  43. National Institute of Food and Drug Safety Evaluation. Quality guidelines of herbal medicine for clinical trial. 2017.12.
  44. Kokudo N, Hasegawa K, Akahane M, Igaki H, Izumi N, Ichida T, et al. Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol Res 2015;45:123-7.
  45. Omata M, Cheng AL, Kokudo N, Kudo M, Lee JM, Jia JD, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma. Hepatol Int 2017;11(4):317-70. https://doi.org/10.1007/s12072-017-9799-9
  46. Lim HS. Malignant tumor Chinese medicine treatment guide. Beijing: People's medical publishing house; 2014, p. 371-99.
  47. Zhou J, Sun HC, Wang Z, Cong WM, Wang JH, Zeng MS, et al. Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China. Liver Cancer 2018;7(3):235-60. https://doi.org/10.1159/000488035
  48. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J of Hepatol 2018;69(1):182-236. https://doi.org/10.1016/j.jhep.2018.03.019
  49. Verslype C, Rosmorduc O, Rougier P, ESMO Guidelines Working Group. Hepatocellular carcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23(Suppl 7):vii41-vii48. https://doi.org/10.1093/annonc/mds165
  50. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, et al. AASLD Guidelines for the Treatment of Hepatocellular Carcinoma. Hepatology 2018;67(1):358-80. https://doi.org/10.1002/hep.29086
  51. Marrero JA, Ahn J, Rajender Reddy K, Americal College of Gastroenterology. ACG clinical guideline: the diagnosis and management of focal liver lesions. Am J Gastroenterol 2014;109(9):1328-47. https://doi.org/10.1038/ajg.2014.213
  52. Chay WY, Tham CK, Toh HC, Lim HY, Tan CK, Lim C, et al. Coriolus versicolor (Yunzhi) Use as Therapy in Advanced Hepatocellular Carcinoma Patients with Poor Liver Function or Who Are Unfit for Standard Therapy. J Altern Complement Med2017;23(8):648-52. https://doi.org/10.1089/acm.2016.0136
  53. Ye X, Lu D, Chen X, Li S, Chen Y, Deng L. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of Shuangbai San for Treating Primary Liver Cancer Patients With Cancer Pain. J Pain Symptom Manage 2016;51(6):979-86. https://doi.org/10.1016/j.jpainsymman.2015.12.330
  54. Xu L, Wang S, Zhuang L, Lin J, Chen H, Zhu X, et al. Jian Pi Li Qi Decoction Alleviated Postembolization Syndrome Following Transcatheter Arterial Chemoembolization for Hepatocellular Carcinoma: A Randomized, Double-Blind, Placebo-Controlled Trial. Integr Cancer Ther 2016;15(3):349-57. https://doi.org/10.1177/1534735415617020
  55. Zhong C, Li HD, Liu DY, Xu FB, Wu J, Lin XM, Guo RP. Clinical study of hepatectomy combined with Jianpi Huayu Therapy for hepatocellular carcinoma. Asian Pac J Cancer Prev 2014;15(4):5951-7. https://doi.org/10.7314/APJCP.2014.15.14.5951
  56. Shimada M, Morine Y, Nagano H, Hatano E, Kaiho T, Miyazaki M, et al. Effect of TU-100, a traditional Japanese medicine, administered after hepatic resection in patients with liver cancer: a multi-center, phase III trial (JFMC40-1001). Int J Clin Oncol 2015;20(1):95-104. https://doi.org/10.1007/s10147-014-0678-2
  57. Tian HQ, Li HL, Wang B, Liang GW, Huang XQ, Huang ZQ, Lang JM, Zhang YP, Chen XZ, Chen YS. Treatment of middle/late stage primary hepatic carcinoma by Chinese medicine comprehensive therapy: A prospective randomized controlled study. Chin J Integr Med 2010;16(2):102-8. https://doi.org/10.1007/s11655-010-0102-3
  58. Yinglu F, Changquan L, Xiaofeng Z, Bai L, Dezeng Z, Zhe C. A new way: alleviating postembolization syndrome following transcatheter arterial chemoembolization. J Altern Complement Med 2009;15(2):175-81. https://doi.org/10.1089/acm.2008.0093
  59. Zhai XF, Liu XL, Shen F, Fan J, Ling CQ. Traditional Herbal Medicine Prevents Postoperative Recurrence of Small Hepatocellular Carcinoma: A Randomized Controlled Study. Cancer 2018;124(10):2161-8. https://doi.org/10.1002/cncr.30915
  60. Chen Q, Shu C, Laurence AD, Chen Y, Peng BG, Zhen ZJ, et al. Effect of Huaier granule on recurrence after curative resection of HCC: a multicenter, randomized clinical trial. Gut 2018;67(11):2006-16. https://doi.org/10.1136/gutjnl-2018-315983
  61. Wu GL, Zhang L, Li TY, Chen J, Yu GY, Li JP. Short-term Effect of Combined Therapy with Jinlong Capsule(金龙胶囊) and Transcatheter Arterial Chemoembolization on Patients with Primary Hepatic Carcinoma and Its Influence on Serum Osteopontin Expression. Chin J Integr Med 2010;16(2):109-13 https://doi.org/10.1007/s11655-010-0109-9
  62. Jeong TY, Lee YW, Cho JG, Yoo HS. Analysis of Clinical Characteristics for 899 Cancer Patients Treated at an Oriental Hospital. Korean J Orient Int Med2010;31(1):102-12.
  63. Capussotti L, Muratore A, Massucco P, Ferrero A, Polastri R, Bouzari H. Major liver resections for hepatocellular carcinoma on cirrhosis: early and long-term outcomes. Liver Transpl 2004;10(2 Suppl 1):S64-8. https://doi.org/10.1002/lt.20035
  64. Lai EC, Fan ST, Lo CM, Chu KM, Liu CL, Wong J. Hepatic resection for hepatocellular carcinoma. An audit of 343 patients. Ann Surg 1995;221(3):291-8. https://doi.org/10.1097/00000658-199503000-00012
  65. Yoo SH, Bae SH. Complications Associated with Transcatheter Arterial Chemoembolization in Patients with Hepatocellular Carcinoma. Korean J of liver cancer study group 2011;11(2):144-8.
  66. Kwak HW, Park JW, Nam BH, Yu A, Woo SM, Kim TH, et al. Clinical outcomes of a cohort series of patients with hepatocellular carcinoma in a hepatitis B virus-endemic area. J Gastroenterol Hepatol 2014;29(4):820-9. https://doi.org/10.1111/jgh.12470
  67. Yan JU, Yao SK. Syndrome Differentiation and Treatment of Primary Hepatocellular Carcinoma in Traditional Chinese Medicine. Chinese Journal of Integrated Traditional and Western Medicine 2010;20(3):189-91. https://doi.org/10.3321/j.issn:1003-5370.2000.03.037
  68. Brierley J, Gospodarowicz M, O'Sullivan B. The principles of cancer staging. Ecancermedicalscience 2016;10:ed61.
  69. Cancer Registration Learning Center [Internet]. Ilsan: Korea Central Cancer Registry; [cited Mar 3]. Available from: https://training.kccr.cancer.go.kr:9443/user/jsp/canceweapon/liver.jsp
  70. Montazeri A, Milroy R, Hole D, McEwen J, Gillis CR. How quality of life data contribute to our understanding of cancer patients' experiences? A study of patients with lung cancer. Quality of Life Research2003;12(2):157-66. https://doi.org/10.1023/A:1022232624891
  71. Cho JH, Son CG, Lee YW, Yoo HS, Seong JH, Kim SY. Current Status of Studies on Cancer-Related Quality of Life Instruments. Korean J Orient Int Med 2006;27(1):84-91.
  72. Choi IS, Yong CS, Lee IH. Readability of Patient Information Leaflets in Clinical Trials. Korean J Clin Pharm2016;26(1):33-9.
  73. Caillet P, Canoui-Poitrine F, Vouriot J, Berle M, Reinald N, Krypciak S, et al. Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer. ELCAPA study. J Clin Oncol 2011;29(27):3636-42. https://doi.org/10.1200/JCO.2010.31.0664
  74. Ministry of Food and Drug Safety. Evaluation of the safety information of the client requesting pharmaceutical clinical trials and considerations for reporting. 2017.8