Chin J Integr Med 2015 Jan;21(1):71-79
• 71 •
EVIDENCE-BASED INTEGRATIVE MEDICINE Shenqi Fuzheng Injection (参芪扶正注射液) for Advanced Gastric Cancer: A Systematic Review of Randomized Controlled Trials LI Jiang (李 江)1,2,3, WANG Jian-cheng (王建成)1,2,3, MA Bin (马 彬)1,2,3, GAO Wei (高 CHEN Peng (陈 鹏)5, SUN Rao (孙 绕)1,2, and YANG Ke-hu (杨克虎)1,2,3
伟)4,
Objective:: To evaluate the effectiveness of Shenqi Fuzheng Injection (参芪扶正注射液, SFI) ABSTRACT Objective Methods:: Randomized controlled trials (RCTs) from combined with chemotherapy for advanced gastric cancer. Methods 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 Results:: Thirteen RCTs involving 860 patients met the selection criteria (all software was applied for data analyses. Results articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3–4, Conclusions:: This oral mucositis at grade 1–2, leucopenia at grade 3–4, and myelo-suppression at grade 1–2. Conclusions systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment. KEYWORDS chemotherapy, Shenqi Fuzheng Injection, advanced gastric cancer, Chinese medicine, systematic review, randomized controlled trial
Gastric cancer is the second threatening cancer-related agent of death worldwide and accounts for 997,000 new diagnoses and 738,000 deaths yearly.(1-3) Its distribution displays geographical variation; China and Japan have relatively higher incidence rates of gastric cancer. (4) In China, over 300,000 new cases and over 200,000 death cases associated with gastric cancer occur annually.(5) It is estimated that gastric cancer currently ranks the third among the most common cancers in China, and will remain to be a most challenging cancer burden in the next few decades.(6) Although surgery is the ready treatment for gastric cancer, the difficulty in poor prognosis still remains stubbornly, such as the high recurrence rate and the low survival rate. In order to lower recurrence rate and improve overall healing rate after surgery, adjuvant therapies have been recommended as the standard care for advanced gastric cancer. However, gastrointestinal toxicity reactions, including leukopenia, thrombopenia,
nausea, vomiting, have already been reported. (7,8) Therefore, how to reduce the toxicity and enhance the best curative effect remains to be a promising challenge. Nowadays, Chinese medicinal herbs have already attracted a great deal of attention due to its low toxicity, curative effects and cost-effective in North-East Asia including China, Japan, and Korea.(9-11) Acceptability of herb medicine, an alternative adjuvant cancer treatment,
©The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2014 1. Evidence-Based Medicine Center, College of Basic Medicine, Lanzhou University, Lanzhou (730000), China; 2. Institute of Integrated Traditional Chinese and Western Medicine, College of Basic Medicine, Lanzhou University, Lanzhou (730000), China; 3. Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou (730000), China; 4. Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California (95817), USA; 5. First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou (510405), China Correspondence to: Prof. YANG Ke-hu, Tel: 86-13893117077, E-mail: [email protected] DOI: 10.1007/s11655-014-1768-8
Chin J Integr Med 2015 Jan;21(1):71-79
• 72 •
has also improved the efficacy of combinational chemotherapy and to help reduce the adverse effects (AEs) related.(12-14) Shenqi Fuzheng Injection (参芪扶正注射液, SFI) is made from two herbs, Radix Astragali and Radix Codonopsis in a ratio of 1:1.(15-17) As an antitumor injection, SFI was approved by the State Food and Drug Administration of the People's Republic of China in 1999.(18) Relative positive results are usually reported by many clinical trials about SFI combined with chemotherapy for the treatment of advanced gastric cancer. However, clinical and statistical evidence of the efficacy of this method is far from evident and confirmed. A systematic review, therefore, carries significant importance to assess whether the SFI combined with chemotherapy for advanced gastric cancer significantly improved quality of life (QOL) and reduced the occurrence of AEs.
METHODS Data Sources and Search Strategy Published papers in English, Chinese, Korean and Japanese about randomized clinical trials (RCTs) of combination treatment (SFI plus chemotherapy) on advanced gastric cancer till December 31, 2012, were searched from various databases, which included the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the Specialized Trials Register of Gastric Cancer, MEDLINE (Ovid), Excerpta Medica Database (EMBASE), Web of Science, the Chinese Biomedical Literature Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), Oriental Medicine Advanced Searching Integrated System (OASIS, Korean Database), and Japanese Institutional Repositories Online (JAIRO, Japanese Database). The details of search terms were used in different databases. The following terms, for example, were presented in MEDLINE: (advanced gastric cancer OR advanced gastric tumors OR advanced gastric malignancy OR "Stomach Neoplasms"[Mesh] ) AND (Astragali OR "astragalin" [Supplementary Concept]). Also potential proceedings books, ongoing studies, conference papers, and graduation thesis were searched and evaluated.
Eligibility Criteria for Considering Studies Types of Studies This review included RCTs that assessed the efficacy of SFI combined with chemotherapy versus chemotherapy alone for advanced gastric cancer, regardless of language, geographic area, publication date, and type of literature. Studies without indicating randomization were considered not randomized and excluded.
Types of Participants The participants must meet the following criteria: (1) an adult person, age>18 years old with advanced gastric cancer diagnosed by tumor markers or computed tomography (CT); (2) no specific restrictions on the neoplasm stage [tumor node metastasis (TNM) stage]; (3) major organs such as heart, liver and kidney, and bone marrow function normally; no contraindication of chemotherapy; (4) general physical condition is good, Karnofsky performance score 60.(19)
Types of Interventions The trials, in which the intervention was SFI combined with chemotherapy versus chemotherapy alone were included; trials investigating immunotherapy, intra-peritoneal chemotherapy or peri-operative chemotherapy were excluded.
Types of Outcome Measures QOL In these studies, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) has been applied to advanced gastric cancer patients to evaluate changes of QOL during the treatment. QOL grading standard has three degrees by necessary adjustment, an increased score >10 is termed as "improvement", a decrease score >10 is classified as "progress", and an increase or decrease score 10 is labeled as "stable".(20)
Improved or Stable Performance Status There are five subgroups: complete remission (CR), partial remission (PR), stable stage, progressive stage and CR+PR.
Weight The difference in weight between pre- and afterchemotherapy are termed "up", "down" or "stable" if the patients gain 1 kg, loss 1 kg, or change
• 71 •
EVIDENCE-BASED INTEGRATIVE MEDICINE Shenqi Fuzheng Injection (参芪扶正注射液) for Advanced Gastric Cancer: A Systematic Review of Randomized Controlled Trials LI Jiang (李 江)1,2,3, WANG Jian-cheng (王建成)1,2,3, MA Bin (马 彬)1,2,3, GAO Wei (高 CHEN Peng (陈 鹏)5, SUN Rao (孙 绕)1,2, and YANG Ke-hu (杨克虎)1,2,3
伟)4,
Objective:: To evaluate the effectiveness of Shenqi Fuzheng Injection (参芪扶正注射液, SFI) ABSTRACT Objective Methods:: Randomized controlled trials (RCTs) from combined with chemotherapy for advanced gastric cancer. Methods 10 databases were searched for this meta-analysis till December 31, 2012 without language restriction. Grey literature and potential unpublished literature was also searched. The key search terms were "chemotherapy", "Shenqi Fuzheng Injection" and "advanced gastric cancer". Criteria were built to select these clinical trials, in which SFI combined with chemotherapy was compared with chemotherapy alone for advanced gastric cancer. The methodological quality of each RCT was assessed using the Cochrane risk of bias tool. RevMan 5.1 Results:: Thirteen RCTs involving 860 patients met the selection criteria (all software was applied for data analyses. Results articles were from Chinese databases). The meta-analysis showed positive results for the use of SFI combined with chemotherapy according to quality of life in terms of the scores when compared with chemotherapy alone. Positive results were also obtained for the combination treatment, in terms of complete remission and partial remission efficacy rate, body weight and decreased adverse events including nausea and vomiting at grade 3–4, Conclusions:: This oral mucositis at grade 1–2, leucopenia at grade 3–4, and myelo-suppression at grade 1–2. Conclusions systematic review found encouraging albeit limited evidence for SFI combined with chemotherapy. However, to obtain stronger evidence without the drawbacks of trial design and the quality of studies, we recommend comparative effectiveness researches to test the effectiveness of combination treatment. KEYWORDS chemotherapy, Shenqi Fuzheng Injection, advanced gastric cancer, Chinese medicine, systematic review, randomized controlled trial
Gastric cancer is the second threatening cancer-related agent of death worldwide and accounts for 997,000 new diagnoses and 738,000 deaths yearly.(1-3) Its distribution displays geographical variation; China and Japan have relatively higher incidence rates of gastric cancer. (4) In China, over 300,000 new cases and over 200,000 death cases associated with gastric cancer occur annually.(5) It is estimated that gastric cancer currently ranks the third among the most common cancers in China, and will remain to be a most challenging cancer burden in the next few decades.(6) Although surgery is the ready treatment for gastric cancer, the difficulty in poor prognosis still remains stubbornly, such as the high recurrence rate and the low survival rate. In order to lower recurrence rate and improve overall healing rate after surgery, adjuvant therapies have been recommended as the standard care for advanced gastric cancer. However, gastrointestinal toxicity reactions, including leukopenia, thrombopenia,
nausea, vomiting, have already been reported. (7,8) Therefore, how to reduce the toxicity and enhance the best curative effect remains to be a promising challenge. Nowadays, Chinese medicinal herbs have already attracted a great deal of attention due to its low toxicity, curative effects and cost-effective in North-East Asia including China, Japan, and Korea.(9-11) Acceptability of herb medicine, an alternative adjuvant cancer treatment,
©The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag Berlin Heidelberg 2014 1. Evidence-Based Medicine Center, College of Basic Medicine, Lanzhou University, Lanzhou (730000), China; 2. Institute of Integrated Traditional Chinese and Western Medicine, College of Basic Medicine, Lanzhou University, Lanzhou (730000), China; 3. Key Laboratory of Evidence-Based Medicine and Knowledge Translation of Gansu Province, Lanzhou (730000), China; 4. Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California (95817), USA; 5. First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou (510405), China Correspondence to: Prof. YANG Ke-hu, Tel: 86-13893117077, E-mail: [email protected] DOI: 10.1007/s11655-014-1768-8
Chin J Integr Med 2015 Jan;21(1):71-79
• 72 •
has also improved the efficacy of combinational chemotherapy and to help reduce the adverse effects (AEs) related.(12-14) Shenqi Fuzheng Injection (参芪扶正注射液, SFI) is made from two herbs, Radix Astragali and Radix Codonopsis in a ratio of 1:1.(15-17) As an antitumor injection, SFI was approved by the State Food and Drug Administration of the People's Republic of China in 1999.(18) Relative positive results are usually reported by many clinical trials about SFI combined with chemotherapy for the treatment of advanced gastric cancer. However, clinical and statistical evidence of the efficacy of this method is far from evident and confirmed. A systematic review, therefore, carries significant importance to assess whether the SFI combined with chemotherapy for advanced gastric cancer significantly improved quality of life (QOL) and reduced the occurrence of AEs.
METHODS Data Sources and Search Strategy Published papers in English, Chinese, Korean and Japanese about randomized clinical trials (RCTs) of combination treatment (SFI plus chemotherapy) on advanced gastric cancer till December 31, 2012, were searched from various databases, which included the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), the Specialized Trials Register of Gastric Cancer, MEDLINE (Ovid), Excerpta Medica Database (EMBASE), Web of Science, the Chinese Biomedical Literature Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), Oriental Medicine Advanced Searching Integrated System (OASIS, Korean Database), and Japanese Institutional Repositories Online (JAIRO, Japanese Database). The details of search terms were used in different databases. The following terms, for example, were presented in MEDLINE: (advanced gastric cancer OR advanced gastric tumors OR advanced gastric malignancy OR "Stomach Neoplasms"[Mesh] ) AND (Astragali OR "astragalin" [Supplementary Concept]). Also potential proceedings books, ongoing studies, conference papers, and graduation thesis were searched and evaluated.
Eligibility Criteria for Considering Studies Types of Studies This review included RCTs that assessed the efficacy of SFI combined with chemotherapy versus chemotherapy alone for advanced gastric cancer, regardless of language, geographic area, publication date, and type of literature. Studies without indicating randomization were considered not randomized and excluded.
Types of Participants The participants must meet the following criteria: (1) an adult person, age>18 years old with advanced gastric cancer diagnosed by tumor markers or computed tomography (CT); (2) no specific restrictions on the neoplasm stage [tumor node metastasis (TNM) stage]; (3) major organs such as heart, liver and kidney, and bone marrow function normally; no contraindication of chemotherapy; (4) general physical condition is good, Karnofsky performance score 60.(19)
Types of Interventions The trials, in which the intervention was SFI combined with chemotherapy versus chemotherapy alone were included; trials investigating immunotherapy, intra-peritoneal chemotherapy or peri-operative chemotherapy were excluded.
Types of Outcome Measures QOL In these studies, the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) has been applied to advanced gastric cancer patients to evaluate changes of QOL during the treatment. QOL grading standard has three degrees by necessary adjustment, an increased score >10 is termed as "improvement", a decrease score >10 is classified as "progress", and an increase or decrease score 10 is labeled as "stable".(20)
Improved or Stable Performance Status There are five subgroups: complete remission (CR), partial remission (PR), stable stage, progressive stage and CR+PR.
Weight The difference in weight between pre- and afterchemotherapy are termed "up", "down" or "stable" if the patients gain 1 kg, loss 1 kg, or change
