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Analysis of Existing Guidelines and Randomized, Controlled, Clinical Trials for Development of [Guideline of Clinical Trial with Herbal Medicinal Product for gastric cancer]

Article information

J Korean Med. 2017;38(3):124-142
Publication date (electronic) : 2017 September 30
doi : https://doi.org/10.13048/jkm.17031
Gajin Han1,2,orcid_icon, Sin Seong1, Sungsu Kim1, Jinsung Kim3, Jae-Woo Park3
1Soram Korean Medicine Hospital
2Soram Bio-Medicine Research Institute
3Department of Gastroenterology, College of Korean Medicine, Kyung Hee University
Correspondence to：한가진(Gajin Han) 서울 강남구 봉은사로 458, 소람한방병원 Tel：+82-70-4803-6635 , Fax：+82-70-8282-7001, E-mail : kmdhgj@soram.kr
Received 2017 August 29; Revised 2017 September 12; Accepted 2017 September 12.

Abstract

Objectives

This study aimed to learn what should be considered in [Guideline of Clinical Trial with Herbal Medicinal Product for Gastric Cancer)] by analyzing the existing guidelines and clinical trials.

Methods

The development committee searched guidelines for herbal medicinal product or gastric cancer developed already. Then, clinical trials for gastric cancer using herbal medicine were searched. The searched trials were analyzed in terms of inclusion and exclusion of participants, intervention, comparator, outcomes and trial design. Then, we compared the results of analysis with the regulations and guidelines of Ministry of Food and Drug Safety to suggest the issue that we will have to consider when making the [Guideline of Clinical Trial with Herbal Medicinal Product for Gastric Cancer].

Results

As a result, few guidelines for anti-tumor agent and clinical trial with herbal medicinal product were searched in the national institution homepage. In addition, 10 articles were searched by using the combination following search term; ‘stomach neoplasm’, ‘herbal medicine’, ‘Medicine, Korean traditional’, ‘Medicine, Chinese Traditional’, ‘TCM’, ‘TKM’, ‘trial’. Most trials included gastric cancer participants with medical history of operation. The type of intervention was various such as decoction, granules, and fluid of intravenous injection. Comparators were diverse such as placebo, conventional treatment including chemotherapy and nutritional supplement. The most frequently used outcome for efficacy was quality of life. Besides, the symptom score, tumor response, and survival rate were used. Safety was investigated by recording adverse events.

Conclusion

We found out some issue by reviewing the existing guidelines and comparing it with clinical trials for gastric cancer and herbal medicinal products. These results will be utilized for developing [Guideline of Clinical Trial with Herbal Medicinal Product for Gastric Cancer].

Keywords: Stomach neoplasm; herbal medicinal product; Clinical trial; Guideline

The List of Searched Guidelines related to Gastric Cancer/Clinical Trial for Herbal Medicinal Product

The Characteristics of Included Study

The Characteristics of Participants in the Included Studies

The Inclusion and Exclusion Criteria of the Selected Studies

The Characteristics of Intervention in the Included Studies

The Characteristics of Comparator in the Included Studies

The Characteristics of Outcomes in the Included Studies

References

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29. Yin SH, Du YQ, Liu B. Clinical study on acupuncture combined with medication in restoration of gastrointestinal functions for postoperative patients with gastric cancer. Zhongguo Zhen Jiu 2009;29(6):459–62.
30. Wang H, Guo LJ, Wu B. Effect of rhubarb combined with enteral nutrition on C-reactive protein and interleukin-6 in peripheral blood of patients with gastric cancer during perioperative period. Zhongguo Zhong Xi Yi Jie He Za Zhi 2008;28(2):101–4.
31. Cai J, Wang H, Zhou S, Wu B, Song HR, Xuan ZR. Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao 2008;6(1):37–40.
32. Wang Y, Wang YT, Lin YH, Zou ZD. Effects of Xuesaitong injection on coagulation function of gastric cancer patients undergoing laparoscopic surgery: a randomized controlled trial. Zhong Xi Yi Jie He Xue Bao 2009;7(6):514–7.
33. Huang CX, Chen LZ, Zhao JG. Influence of chemotherapy with FOLFOX protocol on sex hormones of male patients and the protective effect of herbal medicines for reinforcing Shen and supplementing qi on it. Zhongguo Zhong Xi Yi Jie He Za Zhi 2008;28(11):986–9.
34. Sun DZ, Jiao JP, Zhang X, Xu JY, Ye M, Xiu LJ, et al. Therapeutic effect of Jinlongshe Granule on quality of life of stage IV gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled clinical trial. Chin J Integr Med 2015;21(8):579–86.
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38. Lin H. Guidelines of Diagnosis and Therapy in Oncology with Traditional Chinese Medicine Beijing: Renminweisheng Press; 2014. p. 306–38.
39. Lee JI, Shim KY, Kim HY, Choi SY, Bang DG, Cho KS. Clinical Study of the Efficacy of Combined Western-Oriental Medicine for Gastric Cancer and Hepatocellular Carcinoma. J of Kor Traditional Oncology 2001;7(1):117–129.
40. Lee JH, Kim JG, Jung HK, Kim JH, Jeong WK, Jeon TJ, et al. Synopsis on Clinical Practice Guideline of Gastric Cancer in Korea: An Evidence-Based Approach. Korean J Gastroenterol 2014;63(2):66–81.
41. Kong KH, Ha J, Baek TH. One Case on Diagnosis and Treatment Based on an Overall Analysis of Signs and Symtoms of Stomach Cancer stage IV. Korean J Orient Int Med 2000;21(5):897–902.
42. Sim BS, Choi SH. A Literatural Study on Pattern Identification Type of Stomach Cancer. J of Oriental Medical Pathology 1993;8:295–303.
43. Hwang SY, Ahn SH, Keum KS. Proposal on Supplementation to Oriental Medical Policy for the Revitalization of Oriental Medical Therapy for Stomach Cancer. Korean J Oriental Physiology & Pathology 2009;23(3):528–33.
44. Nationwide Medical College of Oriental Gastroenterology Medicine. Oriental Gastroenterology Seoul: Koonja Publisher Co; 2008. p. 126–36.
45. Lee NH, Cho JH, Son CG, Yoo HS, Lee YW, Yoon DH, et al. Analysis of Studies on Quality of Life according to Cancer Types and Symptoms. Korean J Orient Int Med 2006;27(3):555–60.
46. Lee EH, Park HB, Kim MW, Kang SH, Lee HJ, Lee WH, et al. Analyses of the Studies on Cancer-Related Quality of Life Published in Korea. Radiat Oncol J 2002;29(4):359–66.

Article information Continued

Copyright © 2017 The Society of Korean Medicine all rights reserved

Table 1

The List of Searched Guidelines related to Gastric Cancer/Clinical Trial for Herbal Medicinal Product

Publisher Year Title Characteristics
HR Kim, 2014 Clinical Practice Guidelines of Korean Medicine for Gastric Cancer15)

  1. clinical practice guideline

  2. related to gastric cancer

  3. a research report
HR Kim, 2016 Clinical Practice Guidelines in Korean Medicine for Gastric Cancer16)

  1. clinical practice guideline

  2. related to gastric cancer

  3. a research report
SH Kim, 2006 Study On Development of Assessment Guideline and Endpoints for Clinical Trial with Antitumor Natural Product17)

  1. specific to assessment tool for clinical trial

  2. related to antitumor natural product

  3. a research report
National Institute of food and drug safety evaluation, 2015 Guidelines for clinical trial of anticancer drugs 18)

  1. related to anticancer agents which have toxicity against cancer cell or function of inhibition of cancer cell growth
National Institute of food and drug safety evaluation, 2015 Guidelines for non-clinical trial of anticancer drugs 19)

  1. guideline for non-clinical trial
Korea Food & Drug Administration, 2006 Guideline for evaluation of clinical trial of anticancer drug20)

  1. related to anticancer agents which have toxicity against cancer cell or function of inhibition of cancer cell growth
Ministry of Food and Drug Safety, 2015 Guidelines for Exemption of Anticancer Drug Data in Bridging Study21)

  1. related to data of clinical trial in Korean population
Korea Food & Drug Administration, 2007 General Considerations for Clinical Trials in Herbal Medicine22)

  1. related to general herbal medicine
Korea Institute of Oriental Medicine, 2005 A study on the clinical trial guidelines of herbal medicinal drug23)

  1. related to general herbal medicinal drug

  2. A research report
Industry-Academia Collaboration Foundation, Kyung Hee University, 2006 Research on outcome indicators for clinical trials of herbal medicinal products 24)

  1. related to assessment tool

  2. related to asthma

  3. a research report

Table 2

The Characteristics of Included Study

Title Author Journal, Year Nation Design Group
Clinical observation on treatment of 34 advanced gastric carcinoma patients by chemotherapy of DCF regimen combined with Fuzheng Hewei Decoction Wang Zhongguo Zhong Xi Yi Jie He Za Zhi, 2007 China multicenter, randomized, 2-armed, controlled study

  1. chemotherapy of DCF (docetaxel/cisplatin/5-flu orouracil) + Chinese herbal medicine]

  2. chemotherapy of DCF
Clinical study on acupuncture combined with medication in restoration of gastrointestinal functions for postoperative patients with gastric cancer Yin Zhongg-uo Zhen Jiu, 2009 China single center, randomized, 3-armed, controlled study

  1. conventional treatment

  2. conventional treatment +Chinese herbal medicine (Shi mo decotion)

  3. conventional treatment + Chinese herbal medicine (Shi mo decotion) + acupuncture
Effect of Daikenchuto, a Traditional Japanese Herbal Medicine, after Total Gastrectomy for Gastric Cancer: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase II Trial Yoshikawa J Am Coll Surg, 2015 Japan multicenter, randomized, double-blind, placebo-controlled, phase II Trial

  1. Daikenchuto

  2. placebo
Effect of rhubarb combined with enteral nutrition on C-reactive protein and interleukin-6 in peripheral blood of patients with gastric cancer during perioperative period Wang Zhongguo Zhong Xi Yi Jie He Za Zhi, 2008 China single center, randomized, 3-armed, controlled study

  1. conventional fluid supplement & parenteral nutrition

  2. conventional fluid supplement & parenteral nutrition from the 42nd hour to the 8th day after operation

  3. conventional fluid supplement & parenteral nutrition from the 42nd hour to the 8th day after operation + rhubarb liquid medication
Effect of rikkunshito, a chinese herbal medicine, on stasis in patients after pylorus-preserving gastrectomy Takahashi World J Surg, 2009 Japan single center, randomized, 2-armed, crossover study

  1. initially taking rikkunshito 7.5 g/day before each meal for 4 weeks

  2. initially in the off-treatment stage for 4 weeks and then in on-treatment stage for another

    4 weeks
Effect of Sijunzi Decoction and enteral nutrition on T-cell subsets and nutritional status in patients with gastric cancer after operation: a randomized controlled trial Cai Zhong Xi Yi Jie He Xue Bao, 2008 China single center, randomized, 3-armed, controlled study

  1. isocaloric & isonitrogonous parenteral diet for 9 days

  2. Sjunzi Decoction + treatment of C

  3. isocaloric & isonitrogonous enteral diet which started on the second day after operation, and continued for eight days
Effects of daikenchuto, a Japanese herb, on intestinal motility after total gastrectomy: a prospective randomized trial Akamaru J Gastrointest Surg, 2015 Japan multicenter, randomized, open-labeled, 2-armed, controlled study

  1. daikenchuto + tepid water

  2. tepid water
Effects of Xuesaitong injection on coagulation function of gastric cancer patients undergoing laparoscopic surgery: a randomized controlled trial Wang Zhong Xi Yi Jie He Xue Bao, 2009 China single center, randomized, 2-armed, controlled study

  1. conventional anti-infection and transfusion Treatment

  2. Xuesaitong Injection
Influence of chemotherapy with FOLFOX protocol on sex hormones of male patients and the protective effect of herbal medicines for reinforcing Shen and supplementing qi on it Huang Zhongguo Zhong Xi Yi Jie He Za Zhi, 2008 China single center, randomized, 4-armed, controlled study

  1. FOLFOX

  2. FOLFOX + herbal medicine

  3. herbal medicine

  4. none
Therapeutic effect of Jinlongshe Granule on quality of life of stage IV gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled clinical trial Sun Chinese journal of integrative medicine, 2015 China single center, randomized, double-blind, placebo-controlled study

  1. Jinlongshe Granule

  2. placebo

Table 3

The Characteristics of Participants in the Included Studies

Study Age Sample size Patients
Wang, 2007 - 66 gastric cancer patients diagnosed as stage IV based on American Joint Committee on Cancer (AJCC)
Yin, 2009 - 90 gastric cancer patients who underwent radical operation
Yoshikawa, 2015 20–85 195 gastric cancer patients who underwent total gastrectomy
Wang, 2008 56 gastric cancer patients with a plan to undergo operation
Takahashi, 2009 46–70 11 gastric cancer patients who underwent pylorus-preserving gastrectomy for early gastric cancer (The final stage of gastric cancer of all patients was stage 1 according to the classification of the International Union Against Cancer (UICC))
Cai, 2008 65 gastric cancer patients with nutritional insufficiency who underwent operation
Akamaru, 2015 20–80 81 gastric cancer patients diagnosed as stage I, II, or III with a plan to undergo total gastrectomy with a D2 dissection (permitting preservation of the spleen), Roux-en-Y reconstruction, and R0 surgery
Wang, 2009 42–61 50 gastric cancer patients with a plan to undergo laparoscopic surgery
Huang, 2008 50–70 61 gastric cancer patients with a plan to receive FOLFOX after operation
Sun, 2015 18–90 50 stage IV gastric cancer patients who were suggested to use Jinlongshe Granule in addition to other prescribed Chinese medicine medications. (Staging is based on the International Union for Cancer Control (UICC) Tumor/Node/Metastasis (TNM) Standard Classification)

Table 4

The Inclusion and Exclusion Criteria of the Selected Studies

Study Inclusion Criteria Exclusion Criteria
Wang, 2007 Who diagnosed as stage IV gastric cancer by endoscopy and biopsy nonespecific
Yin, 2009

  1. Who diagnosed as gastric cancer

  2. who could undergo radical operation

  3. who had normal gastric function before operation

  1. who have severe metabolic disorders such as hypertension, diabetes

  2. who had abnormal liver and kidney function before operation

  3. who had metastasis on the other organ such as peritoneum, liver, and lung

  4. who receive enteral nutrition treatment

  5. who had other surgical disorder that may affect the result of study
Yoshikawa, 2015

  1. eligible patients had gastric cancer and were planning open total gastrectomy with Roux-en-Y reconstruction

  2. had an Eastern Cooperative Oncology Group performance status of 0 to 1

  3. were capable of orally taking test reagents

  4. were aged from 20 to 85 years

  5. had sufficient function of vital organs (including bone marrow, heart, liver, kidneys, and lungs)

  6. were in an adequate general condition to undergo total gastrectomy

  7. were inpatients during the study period

  8. provided written informed consent

  1. patients whose medical histories included any of the following were excluded.

    1. previous laparotomy (except appendectomy)

    2. previous intestinal resection

    3. ulcerative colitis or Crohn’s disease

    4. emergency operation

    5. a diagnosis of cancer before the current gastric carcinoma

    6. chemotherapy in the 4 weeks before surgery or during the trial period

    7. intake of other kampo medicines in the 4 weeks before surgery.

  2. patients who were pregnant or possibly pregnant and those who had synchronous cancers were also excluded.
Wang, 2008

  1. who diagnosed as gastric cancer or postoperative state by endoscopy

  1. who had abnormal function of significant organs

  2. who had metabolic disease or infectious disease

  3. who had immune deficiency

  4. who had not condition for operation

  5. who had not received radiotherapy or chemotherapy

  6. who received unspecified nutrient solution or nutritional support
Takahashi, 2009

  1. who underwent PPG for early gastric cancer

  2. The final stage of gastric cancer of all patients was stage 1 according to the classification of the International Union Against Cancer (UICC).

  1. These patients had no significant associated diseases such as cirrhosis, renal failure, pulmonary diseases, or cardiac diseases.

  2. They had no postoperative complications including leakage and intestinal obstruction, nor had they received chemotherapy.
Cai, 2008

  1. who had operation for gastric cancer

  2. who had nutritional deficiency according to following criteria: patients’ body weight decreased by> 5% 3 months before admission or 6 months body weight decreased> 10%, level of albumin <35 g/L, level of transferrin <2 .0 g/L. (The presence of any of the above, identified as the existence of malnutrition)

  1. Those who do not meet the inclusion criteria

  2. There are other important organ dysfunction, surgical contraindications

  3. metabolic disease patients or accompanied by infectious diseases

  4. immunodeficiency

  5. patients who receive radiation or chemical treatment before and after surgery

  6. who had distant metastasis of the tumor confirmed newly during surgery, so could not undergo radical surgery or combined with the same line of organ resection

  7. who use non-designated nutrient solution or nutritional support within perioperational period
Akamaru, 2015

  1. who had no previous cancer treatment or past history of any other cancer

  2. who aged between 20 to 80 years

  3. who was scored 0 or 1 by an Eastern Cooperative Oncology Group performance status

  4. who had adequate organ functions.

  1. patients that showed any hepatic, peritoneal, or distant metastasis or any positive tumor cells in cytological examinations of peritoneal fluids

  2. emergency surgery

  3. other active malignancies

  4. morbid cardiopulmonary disease

  5. severe liver-kidney dysfunction

  6. a history of laparotomy (except appendectomy)

  7. intestinal obstruction.
Wang, 2009

  1. who underwent laparoscopic surgery for gastric cancer

  2. who had laboratory tests without bleeding tendency or coagulation disorders

  3. who had a history of no thromboembolic disease within 3 months before surgery

  4. who had not thrombosis in the lower limb deep vein by ultrasound examination before operation

  1. who administered anticoagulant drugs within recent 2 weeks

  2. who had severe primary cardiovascular, liver and kidney disease

  3. who had severe diabetes mellitus

  4. who experience laparotomy due to any reasons during laparoscopic surgical procedures

  5. who receive transfusion before or after operation

  6. who had allergic reaction to Xuesaitong Injection
Huang, 2008

  1. who are male patients

  2. who diagnosed as gastric cancer confirmed pathologically

  1. who had medical history of pituitary and gonadal diseases
Sun, 2015

  1. patients of either sex aged 18–90 years whose diagnosis was in accordance with stage IV gastric cancer

  2. patients with a Karnofsky performance score (KPS) > 30

  3. patients whose expected survival was > 3 months

  4. patients who signed informed consent willing to receive Chinese medicine anti-tumor therapy

  1. Patients not in accordance with the above inclusion criteria

  2. patients with metastatic gastric cancer

  3. patients whose gastric cancer was pathologically confirmed as adenosquamous carcinoma, squamous cell carcinoma, carcinoid carcinoma, small cell carcinoma, gastric malignant lymphoma, or gastric stromal tumor

  4. patients with multiple cancers

  5. patients associated with other severe illnesses, such as New York Heart Association Classification > Class 3 and K/Kidney Disease Outcome Quality Initiative Classification > Stage 3

  6. patients who participated in other clinical trials in recent three months

Table 5

The Characteristics of Intervention in the Included Studies

Study Intervention Contents & Dose Period
Wang, 2007 chemotherapy + Chinese herbal medicine

  1. Chemotherapy: DCF (docetaxel/cisplatin/5-fluorouracil)

  2. Fuzheng Hewei Decoction: Codonopsis pilosula Nannfeldt 15g, Radix Astragali 30g, Broadleaf Liriope 10 g, Panax quinquefolium 6g, Atractylodes macrocephala Koidzumi 10g, Poria cocos Wolf 10g, Pinellia ternata 10g, Citrii Unshius Pericarpium Viride 6g Citri Unshius Pericarpium 6g, Angelica gigas Nakai 10g, Coicis Semen 10g, Akebia quinata 15g Actinidia arguta 15g, Bletilla striata 10 g, Aurantii Fructus Immaturus 6g, Curcuma longa Linne 10g, Phyllostachyos Caulis in Taeniam 10g, Coptis chinensis 6g Coptis chinensis 10g, Trogopterorum Faeces 10g

 6 weeks
Yin, 2009 conventional treatment + Chinese herbal medicine

  1. Conventional treatment:

    1. fasting water, continuous gastrointestinal decompression, intravenous fluid supplement, to ensure adequate heat, to maintain the balance of water and electrolyte, social supplements and trace elements such as vitamin supplements, and nutritional support therapy.

    2. paclitaxel + levofloxacin (IV daily)

    3. ammonia Alcohol Injection (IV daily, inhalation)

  2. Shi mo decotion

Aucklandiae Radix: Lindera strychnifolia: Aurantii Fructus Immaturus: Areca catechu = 2:3:3:3		 10 days
Yoshikawa, 2015 Daikenchuto Daikenchuto (Tsumura, Tokyo, Japan) is a traditional Japanese herbal medicine composed of 4 crude drugs: dried Japanese pepper, processed ginger, ginseng radix, and maltose powder.
15 g/day		 12 days
Wang, 2008 conventional fluid supplement & parenteral nutrition + rhubarb liquid medication

  1. conventional fluid supplement & parenteral nutrition : protein 20 g, fat 19 g, carbohydrate 61.5 g, dietary fiber 7.5 g, minerals and vitamins. At the 18th and 42th hour after operation, 50 mL of warm saline was injected slowly from the stomach tube. After 42 h, the patients were injected with 10 ~ 15 cm nasal feeding tube (Drip 30 ~ 50 mL/h), 250 mL (drip 80 ~ 100 mL/h) on day 4, postoperative day 2 and day 3 Day 500 ~ 1000 mL (drip 100 ~ 150 mL/h), continued to the first 8 days after surgery, with the infusion pump evenly and gradually transition to semi-liquid diet and general food; within a few days after the daily liquid volume, Heat and nitrogen deficiencies are partially supplemented by parenteral routes

  2. rhubarb : The rhubarb 10 g crushed into coarse powder, 100 °C boiling water 100 mL soak for 15 min, gauze filter made of rhubarb liquid, dry to 37 ~ 38 °C stand. Patients were treated with rhubarb solution 100 mL orally at 1 day before operation. The patients were treated with rhubarb 50 mL nasal feeding tube at a rate of 10 mL/min and closed for 1 h for gastrointestinal decompression.

 8 days
Takahashi, 2009 rikkunshito Rikkunshito (Tsumura, Tokyo, Japan), a traditional herbal medicine, is a mixture of dried Atractyloidis lanceae rhizoma (component ratio = 4), Ginseng radix (= 4), Pinelliae tuber (=4), Hoelen (=4), Zizyphi fructus (=2), Aurantii nobilis percarpium (=2), Glycyrrhizae radix (=1), and Zingiberis rhizome (=0.5)
initially taking rikkunshito 7.5 g/day before each meal		 4 weeks
Cai, 2008 Sjunzi Decoction + isocaloric & isonitrogonous enteral diet

  1. Sjunzi Decoction :Codonopsis pilosula Nannfeldt 20g, Atractylodes macrocephala 20g, Poria cocos Wolf 20g, Glycyrrhiza uralensis Fischer 10g, 100mL/day

  2. isocaloric & isonitrogonous enteral diet: protein 20 g, fat 19 g, carbonized compound 61.5 g, dietary fiber 7.5 g, mineral and various vitamins, providing 500 kcal of calories.

 9 days
Akamaru, 2015 daikenchuto + tepid water 2.5 g of daikenchuto (Tsumura & Co., Tokyo, Japan), taken orally with 20-ml tepid water three times per day, starting the day after the operation, when oral intake was allowed.
7.5g/day		 12 weeks
Wang, 2009 Xuesaitong Injection + conventional anti-infection and transfusion treatment

  1. Xuesaitong Injection: 400mg with 5% Glucose injection 250 mL, intravenous infusion, 1 times/d, continuous administration (18 g/day)

  2. conventional anti-infection and transfusion treatment: routine anti-infection (levofloxacin, metronidazole), rehydration (glucose, amino acid, lipid milk, etc.)

 6 days
Huang, 2008

  1. chemotherapy + herbal medicine

  2. herbal medicine

  1. Chemotherapy: FOLFOX

  2. Herbal medicine: Radix Astragali 9–15 g, Polygonatum falcatum 12–18g, Ligustrum japonium Thunb 9–15 g, Panax ginseng 3–9 g Liriope platyphylla 9–15 g etc

 10 days
Sun, 2015 Jinlongshe Granule Arisaematis Rhizoma Preparatum 15 g, Pinelliae Rhizoma Preparatum 15 g, Cremastrae Pseudobulbus 15 g, Paridis Rhizoma 30 g and other herbal medicines 12 weeks

Table 6

The Characteristics of Comparator in the Included Studies

Study Comparator
Wang, 2007 Chemotherapy: DCF (docetaxel/cisplatin/5-fluorouracil)
Yin, 2009 A: conventional treatment

  1. fasting water, continuous gastrointestinal decompression, intravenous fluid supplement, to ensure adequate heat, to maintain the balance of water and electrolyte, social supplements and trace elements such as vitamin supplements, and nutritional support therapy.

  2. paclitaxel + levofloxacin (IV daily)

  3. ammonia Alcohol Injection (IV daily, inhalation)

C: conventional treatment + Chinese herbal medicine (Shi mo decotion) + acupuncture
Yoshikawa, 2015 Daikenchuto placebo : The placebo consisted of dextrin, lactose, and various food additives. The placebo formulation matched the texture and other characteristics of the active drug.
Wang, 2008 enteral nutrition : protein 20 g, fat 19 g, carbohydrate 61.5 g, dietary fiber 7.5 g, minerals and vitamins. At the 18th and 42th hour after operation, 50 mL of warm saline was injected slowly from the stomach tube. After 42 h, the paients were injected with 10 ~ 15 cm nasal feeding tube (Drip 30 ~ 50 mL/h), 250 mL (drip 80 ~ 100 mL/h) on day 4, postoperative day 2 and day 3 Day 500 ~ 1000 mL (drip 100 ~ 150 mL/h), continued to the first 8 days after surgery, with the infusion pump evenly and gradually transition to semi-liquid diet and general food; within a few days after the daily liquid volume, Heat and nitrogen deficiencies are partially supplemented by parenteral routes
Takahashi, 2009 initially in the off-treatment stage for 4 weeks and then in on-treatment stage(taking rikkunshito 7.5 g/day before each meal for 4 weeks) for another 4 weeks
Cai, 2008 A: isocaloric & isonitrogonous parenteral diet for 9 days
C: isocaloric & isonitrogonous enteral diet which started on the second day after operation, and continued for eight days
* isocaloric & isonitrogonous parenteral diet: protein 20 g, fat 19 g, carbonized compound 61.5 g, dietary fiber 7.5 g, mineral and various vitamins, providing 500 kcal of calories.
Akamaru, 2015 20-ml tepid water three times per day, starting the day after the operation operation, when oral intake was allowed.
Wang, 2009 conventional anti-infection and transfusion treatment : routine anti-infection (levofloxacin, metronidazole), rehydration (glucose, amino acid, lipid milk, etc.)
Huang, 2008 A: FOLFOX
D: none
Sun, 2015 The placebo was made of starch, dextrin and bitter agent, whose odor and taste were similar to Jinlongshe Granule, and the package was the same as Jinlongshe Granule.

Table 7

The Characteristics of Outcomes in the Included Studies

Study Outcome
Wang, 2007

  1. Response Evaluation Criteria in Solid Tumors (RECIST)

  2. adverse event

  3. quality of life according to Karnofsky performance status scale

  4. 1-year survival rate
Yin, 2009

  1. symptom score according to ‘Chinese medicine new drug clinical research guidelines’

  2. white blood cell count,

  3. neutrophil count,

  4. monocyte count,

  5. lymphocyte number
Yoshikawa, 2015

  1. Primary Outcome: time from the end of operation (tracheal tube extubation) until first flatus and defecation, and frequency of defecation per day after surgery

  2. Secondary outcome:

    1. quality of life according to the Gastrointestinal Symptom Rating Scale (GSRS) and Functional Assessment of Cancer Therapy Gastric (FACT-Ga)

    2. serum C-reactive protein levels

    3. presence or absence of severe postoperative bowel movement disorder

    4. presence or absence of postoperative ileus.

    5. Adverse events
Wang, 2008

  1. bowel sound

  2. C-reactive protein(CRP)

  3. IL-6
Takahashi, 2009

  1. Gastrointestinal Quality-of-Life Index (GIQLI)

  2. emptying study (dual-phase scintigraphy)
Cai, 2008

  1. T cell subset

  2. albumin

  3. prealbumin

  4. transferrin
Akamaru, 2015

  1. gut motor functions during the hospital stay (time to first bowel movement and the frequency and properties of stools

  2. a radiographic quantification of bowel gas

  3. QOL assessment (GSRS questionnaire)

  4. the incidence of postoperative intestinal obstruction

  5. adverse events related to the DKT medicine
Wang, 2009

  1. prothrombin time

  2. activated partial thromboplastin time

  3. fibrinogen,

  4. international normalized ratio

  5. incidence of deep vein thrombosis
Huang, 2008

  1. Luteinizing hormone

  2. Estradiol

  3. PRL

  4. progesteron

  5. follicle-stimulating hormone
Sun, 2015

  1. Quality of Life Questionnaire C30 (QLQ-C30)score

  2. Karnofsky performance status scale (KPS)

  3. Chinese Medicine(CM) score

  4. Laboratory tests included blood and urine routine, liver/kidney function and tumor biomarkers.

  5. Adverse events