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1 대한한방내과학회지제 39 권 4 호 (2018 년 9 월 ) J. Int. Korean Med. 2018;39(4): 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) 김민서, 정유진, 홍상훈동의대학교부속한방병원한방내과 Clinical Effectiveness of Traditional Herbal Medicine in the Treatment of Chemotherapy-induced Leukopenia: A Systematic Review and Meta-analysis of Randomized Clinical Trials Min-serh Kim, Yu-jin Jung, Sang-hoon Hong Dept. of Korean Internal Medicine, Dong-Eui University Hospital ABSTRACT Objectives: We performed a systematic review and meta-analysis to explore the recent clinical research trends regarding the effects of traditional herbal medicine (THM) on chemotherapy-induced leukopenia. Methods: Randomized controlled trials that verified effects of herbal medicine treating chemotherapy induced leukopenia were included in the study. A literature search was performed in the English, Chinese, and Korean databases for papers published from January 1, 2007, to September 1, The selected literature was assessed by Cochrane s Risk of Bias (RoB). Results: Forty-two of 232 randomized controlled trials met the inclusion criteria. The most commonly used herbal prescriptions called 升白湯 (shengbai decoction) which means elevating the numbers of White blood cells (WBCs). And the mostly included herbs such as Astragali Radix, Angelicae Gigantis Radix, Atractylodis Rhizoma Alba, Codonopsis Pilosulae, Glycyrrhizae Radix, Ligustri Lucidi Fructus are commonly used to elevate qi, blood and yin. The count of WBC in peripheral blood, the level of leukopenia presented in WHO (World Health Organization), and clinical symptoms were used to evaluate the treatments. The effective rate was % and the effectiveness was significantly higher in the intervention group than in the control group in 38 articles (p<0.05). No serious adverse events were reported. Only five articles (5/42, 11.9%) were rated as having adequate methodological quality with a low level of bias. Conclusion: Some traditional herbal medicines may be effective as therapeutic treatments for chemotherapy-induced leukopenia, but the majority of reviewed studies were of poor quality. The present findings need to be confirmed by rigorously conducted high-quality trials, including pharmacokinetic studies, to confirm the absence of interactions between traditional herbal medicine agents and chemotherapy. Key words: chemotherapy, leukopenia, herbal medicine, systemic review, meta-analysis Ⅰ. 서론 투고일 : , 심사일 : , 게재확정일 : 교신저자 : 홍상훈부산광역시부산진구양정로 62 동의대학교부속한방병원 2 층한방 1 내과 TEL: FAX: shhong@demc.or.kr 통계청에서보고한 2016년대한민국사망원인통계자료에따르면암 ( 악성신생물 ) 은심장, 뇌혈관질환을제치고여전히성인사망률에있어부 520

2 김민서 정유진 홍상훈 동의 1위자리를차지하고있다 1. 현대의학에서활용하는암치료의방법은크게수술, 방사선요법, 항암제로분류된다. 그중에서도항암화학요법의치료는수술, 방사선요법과는다르게전신에영향을미치는치료로서, 암이있는부위뿐만아니라어딘가에전이되었을지모를미세암종까지도공격할수있기때문에전이의위험은크게줄어들수있는반면부작용또한전신에걸쳐나타나양날의검과같은특징을가진다 2. 항암화학요법후에야기되는부작용중골수억제에의한백혈구감소증혹은호중구감소증은가장흔한항암제투여에의한독성반응으로, 면역력감소로인해심각한감염의발생위험도를증가시켜생명을위협할수있다. 그러므로이러한백혈구감소증의예방과호중구수치의회복기간의감축이가능하다면, 주기적항암치료의지속은물론병원에서의입원기간단축및감염으로인한환자의이차질병을피함과동시에이로인한치사율의감소를기대할수있다 3. 현재국내의료는양방과한방의이원화체계로, 항암치료를받으면서동시에한약을복용하는중국이나일본과는상황이많이다르다. 중국의경우양 한방결합형태의암치료전문병원및연구소를갖추고양방항암제와한방항암제혹은보조제로서의한방제제를병용함으로써그상승효과를도모하는적극적이며독자적위치의한방치료가자리매김하고있고 4, 일본의경우는양방과한방의일원화체계를구축하고있으나한방치료가암치료의보조적분야에속해있고단독으로는항종양효과를기대할수없다고생각하는단계이며, 특별한한의치료법이존재하는것이아닌일반적으로쓰이는처방을임상증상에맞추어쓰는것이원칙으로하고있다 5. 하지만우리나라의한의원혹은한방병원에내원하는암환자들은통상적항암치료이후나타나는후유증관리를위한것으로, 예방적의미보다는부작용의치료적개념으로서한의치료가주가되는것이현실이다. 항암화학유도백혈구감소증에대한국내한의학계연구는단일약물 ( 황기 ) 에관한연구 6-8, 단일한약의효과연구 3,9,10, 침치료에대한문헌고찰 11, 중의학치료에관한문헌고찰 12 이있었으며, 한약의치료적의미에대한최신연구의메타분석이나체계적고찰은이루어지지않았다. 이에저자는본연구에서최근 10년간발표된임상논문을분석하여, 향후국내에서항암치료로유발된백혈구감소증에대한한약치료연구의기초자료를마련하는데도움이되고자본연구를진행하였다. Ⅱ. 연구대상및방법 1. 정보원및검색전략논문검색은대표적중국논문검색데이터베이스인중국학술정보원 CNKI(Chinese National Knowledge Infrastructure Database, including China Academic Journals Full-text Database(CJFD), China Doctoral Dissertations and Masters Theses Full-text Database (CDMD) 와영문데이터베이스검색사이트인 Pubmed, Embase, Cochrane Library 그리고국내데이터베이스인국가과학기술정보센터 (National Discovery for Science Leaders, NDSL), 한국교육학술정보원 (Research Information Sharing Service, RISS), 전통의학정보포털 (Oriental Medicine Advanced Searching Integrated System, OASIS), 한국학술정보 (Korean studies Information Service System, KISS) 의총 8개검색원에서 2017년 9월 12일검색을시행하였다. 논문을검색할때에는언어의제한없이 2007 년 1월 1일부터 2017년 9월 1일까지발간된논문전체를대상으로선별하였다 (Table 1-5). 521

3 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) Table 1. Search Strategy on Pubmed #1 cancer"[tiab] OR tumor"[tiab] OR carcinoma"[tiab] #2 chemotherapy"[tiab] OR induced"[tiab] #3 leukopenia"[tiab] OR neutropenia"[tiab] OR white blood cell reduction"[tiab] OR neutrophil reduction [tiab] #4 herbal medicine"[tiab] OR chinese medicine"[tiab] OR herb*"[tiab] OR decoction"[tiab] OR powder"[tiab] #5 #1 AND #2 AND #3 AND #4 Table 2. Search Strategy on Embase #1. cancer':ab,ti OR tumor':ab,ti OR carcinoma':ab,ti #2. chemotherapy':ab,ti OR induced':ab,ti #3. leukopenia':ab,ti OR neutorpenia':ab,ti OR white blood cell reduction':ab,ti OR neutrophil reduction':ab,ti #4. herbal medicine':ab,ti OR chinese medicine':ab,ti OR herb*':ab,ti OR decoction':ab,ti OR powder':ab,ti #5. [randomized controlled trial]/lim #6. [ ]/py #7 #1 AND #2 AND #3 AND #4 AND #5 AND #6 Table 3. Search Strategy on Cochrane Library #1 cancer":ti,ab,kw OR tumor":ti,ab,kw OR carcinoma":ti,ab,kw #2 chemotherapy":ti,ab,kw OR induced":ti,ab,kw #3 leukopenia":ti,ab,kw OR neutropenia":ti,ab,kw OR white blood cell reduction":ti,ab,kw OR neutrophil reduction":ti,ab,kw #4 herbal medicine":ti,ab,kw OR chinese medicine":ti,ab,kw OR herb*":ti,ab,kw OR powder":ti,ab,kw #5 randomised :ti,ab,kw OR randomized :ti,ab,kw #6 #1 AND #2 AND #3 AND #4 AND #5 Table 4. Search Strategy on NDSL, RISS, OASIS, KISS ( 癌 cancer tumor carcinoma 암 종양 ) (neutropenia leukopenia leucopenia 백혈구감소증 호중구감소증 골수억제 ) ( 화학 항암 chemotherapy induced) (oriental medicine chinese medicine herb* decoction 한약 ) (RCT randomised randomized 무작위 ) Table 5. Search Strategy on CNKI (CJFD, CDMD) 검색어 : , [ 중의학, 중약학, 중서의결합 ], 중영문혼합검색 [ 癌 OR 瘤 OR 肿瘤 OR 肿 OR cancer OR tumor OR carcinoma)] AND [( 中性粒细胞减少 OR 白细胞减少 OR 中性粒细胞降低 OR 白细胞降低 OR neutropenia OR leukopenia OR white blood cell reduction OR neutrophil reduction ( 主題 )] AND [ 化疗 OR chemotherapy OR induced ( 主題 )] AND [ 中药 OR 汤 OR 饮 OR 散 OR 丸 OR 方 OR herbal medicine' OR chinese medicine' OR powder OR pill OR prescriptions OR capsule OR herb OR decoction ( 主題 )] AND ( 随机 OR 对照 OR randomized OR randomised) ti : title, ab : abstract, lim : limited, py : publication years (including), kw : keyword 2. 선정및배제기준검색된논문에서사람을대상으로한무작위대조군연구 (randomized controlled trial, RCT) 를포함하고, 단일군전후연구, 종설논문, 단행본, 인터넷자료혹은비출판자료는제외하였다. 대상자는모두병리학적암진단기준에따라암으로진단받은환자이며, 암의위치, 병기, 병리학적유형등에따라치료군과대조군모두항암화학치료를받은환자로국한하였다. 또한, 항암화학치료전백혈구수는정상이며, KPS(Karnofsky performance status) 522

4 김민서 정유진 홍상훈 점수 60점이상, 기대예명이 3달이상인경우를대상으로하였다. 단, 정신질환이나중증장애자, 심, 간, 신, 폐기능의중증질환이나조혈계통의질환이있는경우, 임신중이거나수유중인여성환자는대상에서제외되었다. 또한한약을중재로사용하여백혈구감소환자를치료한연구를포함하였다. 즉, 한약단독군과양약단독군을비교한연구, 한약과양약병용군과양약단독군을비교한연구혹은한약단독군과무처치군을비교한연구를대상으로선정하였다. 다만한약의제형에대하여탕약, 환 ( 丸 ), 과립 ( 顆粒 ) 형태만을연구대상으로하였고, 캡슐형 ( 膠囊, capsule) 은시판된생약성분의의약품형태인연구가포함되어국내한의학의통상치료범주에속하지않아제외하기로하였다. 또한침, 뜸이병용된연구역시대상에서제외되었다. 결과변수로는다음중적어도하나를사용한연구를포함하였다. (1) 화학치료이전과이후의말초혈액의백혈구수혹은호중구수에대한객관적측정지표, (2) 백혈구수회복정도에대한유효율, (3) WHO 기준백혈구감소증혹은호중구감소증분류의등급에대한객관적측정지표, (4) 삶의질척도 (KPS, ECOG(Eastern Cooperative Oncology Group) 점수 ), (5) 이상반응 3. 문헌선택및자료분석두명의독립된연구자 (MSK, YJJ) 는검색된문헌의서지정보를각각 Endnote X 7.2.1을활용하여정리및관리하였고검색결과를상호비교하여누락되는연구가없는지확인하였다. 1차로제목과초록을통해연구대상, 중재및무작위대조군연구구조와관련없는논문을배제하고, 선정된논문에대해원문을다운로드하여추가적정보확인후선정기준에부합하지않는논문들은제외하였다. 또한, 두명의연구자는독립적으로최종선정된연구들의연구설계, 연구대상자, 진단도구, 평가지표, 주요결과등에대해각각분석 하였다. 추출된자료는서지학적정보, 암의유형과진단기준, 중재, 결과변수, 비뚤림위험등의항목에따라정보를추출하였다. 4. 개별연구의비뚤림위험본연구에서는코크란비뚤림위험도구 (Cochrane s Risk of Bias, 이하 RoB) 를이용한비뚤림위험측정을시행하고, 메타분석에포함하였다. 코크란비뚤림위험도구는체크리스트방식과영역평가방식의결합된형태를갖추고있으며, 문항을단순화한반면같은문항에대한주관적이거나자의적인답변의가능성을최소화하고평가자의연구방법론에대한이해도와숙련도에따른평가결과의변동을최소화하기위한노력을기울여만들어진도구이다. 각문항에대하여문헌의본문에어떠한내용이있는지에따라비뚤림위험이 높음 (high risk of bias), 낮음 (low risk of bias) 혹은 불확실 (uncertain) 로판정한다. 무작위대조임상연구에서비뚤림종류는선택비뚤림, 실행비뚤림, 결과확인비뚤림, 탈락비뚤림, 보고비뚤림의다섯가지이다. RoB도구는무작위배정순서생성, 배정순서은폐, 참여자와연구자의눈가림, 결과평가자의눈가림, 불완전한결과의처리, 선택적결과보고, 잠재적인다른비뚤림위험의 7가지영역으로평가한다 요약측정치및자료분석자료의합성과분석은 Review Manager(RevMan) 5.3을이용하였다. 이분형변수에대해서는비교위험도 (odds ratio, OR) 와양측 95% 신뢰구간 (confidence intervals, CIs) 을이용하여표시하였고, 연속형변수의경우는평균차 (mean difference, MD) 를 95% 신뢰구간 (CIs) 과함께표시하였다. 교차연구 (crossover trials) 를위해, 첫번째연구기간의결과값만을포함하였다. 본연구는항암유도백혈구감소증에대한특정한약의치료적효과에관한연구가아닌한약전 523

5 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) 반의효과를검증하기위한것으로, 중재에는다양한종류의한약이포함되었기때문에각연구간의높은이질성은불가피하다. 한의학은같은질병과증상에대해서도한의학적변증에따라한약을처방하는것이특징이자장점이며, 동시에이는엄격한통제하에시행되는비교연구에있어서는결정적인단점으로작용한다. 정량적분석이이루어지는메타분석에서는요약자료 ( 처리효과에대한측정값및해당신뢰구간 ) 의크기차이에의해통계적이질성을가진다. 보통연구간의통계적이질성의존재여부평가는 Chi 2 검정혹은 Higgin s I 2 통계를통해시행하고, α( 유의수준 ) 0.1 혹은 I 2 =50% 를기준값으로효과모형 (effect model) 을선택하게된다 14. 연구결과의분석시, 통계적으로유의한이질성이존재하지않을때에는고정효과모형 (fixed effect model) 에의한분석결과를제시하지만, 본연구의메타분석에서는발생한이질성에대해서는무시하고연구간의정성적혹은정량적이질성이크다는전제하에좀더보수적인결과인변량효과모형 (random effect model) 을활용하였다. 이질성이크고포함된연구의수가많은경우는확고한결과평가를위하여중재의유형에따른하위그룹분석을시행하였다. Ⅲ. 결과 1. 연구선택 8개의데이터베이스로부터, 검색을통해 CNKI (n=200), Pubmed(n=14), Embase(n=7), Cochrane Library(n=2), NDSL(n=9), RISS(n=0), OASIS (n=0), KISS(n=0) 등총 232편의논문이검색되었다. 1차로제목과초록을보고 RCT가아닌연구 (n=24), 백혈구감소증환자에대한경우가아닌연구 (n=31), 한약을중재로사용하지않은연구 (n=36), 한약대한약을비교한연구 (n=1), 백혈구나호중구수치의변화와관계없는연구 (n=16), 중복된논문 (n=2) 을제외하고 122편을 1차선별하였다. 선별된논문에대하여원문을확보하여다시한번추가적인정보를얻어포함기준에맞지않는논문을제외하였다. RCT가아닌연구 (n=3), 백혈구감소증으로확인하기힘들거나진단받지않은환자를대상으로한연구 (n=63), 한약이중재로사용되지않은연구 (n=10), 문헌전체에접근불가한연구 (n=3) 까지총 80편을제외하여, 최종적으로 42편의무작위임상시험 (RCTs, N=4097) 연구가체계적고찰에포함되었다. 이중 4편 (9.52%) 은학위논문이었으며, 나머지 38편은중국저널에서발행된문헌이다 (Fig. 1). 524

6 김민서 정유진 홍상훈 Fig. 1. Flow chart of the trial selection process (PRISMA). 2. 선정된문헌의분석 1) 연구설계연구는모두중국에서수행되었다. 이중 40편이 2-arm study로한약치료군과지지요법 ( 양약 ) 치료군의비교연구가가장높은빈도를차지했으며 (n=31), 다음으로한약과지지요법 ( 양약 ) 병용군과지지요법 ( 양약 ) 단독군을비교한연구 (n=4), 한약과양약치료군을비교한연구 (n=2), 한약과양약병용군과양약치료군비교연구 (n=2), 한약 과무처치군을비교한연구 (n=1) 순으로많았다. 3-arm study는 2편으로, 한약치료군과한약-양약병용치료군, 양약단독치료군을비교한연구 1편과한약 ( 산제 ) 치료군과한약 ( 탕약 ) 치료군그리고양약단독치료군으로한약의제형에따라분류한연구 1편을포함된다. 연구대상자수는 32명에서 210명으로다양했으며평균 97.55명이었다. 모든환자는진단된질환에따라항암화학치료 (chemotherapy, CTh) 를받았다. 525

7 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) 2) 대상 (1) 진단도구및변증도구백혈구감소증은혈중백혈구수치가정상수치 ( 혈액 1L당 개 ) 이하로감소되어있는상태로정의되며, 여러차례의검사를통해진단된다. WHO에서는백혈구수가 ( ) 10 9 /L일때 Ⅰ 도, ( ) 10 9 /L일때 Ⅱ도, ( ) 10 9 /L일때 Ⅲ도, (1.0) 10 9 /L 미만일때 Ⅳ도로분류한다. 호중구감소증은 CTCAE(The Common Terminology Criteria for Adverse Events) 15 의분류를통해확인가능하다. CTCAE는약물사용후부작용에대해평가하는도구로항암화학치료에사용되는항암제에따른예상되는부작용을판단할수있는하나의지표로서 Grade I-V로나누어, 경도 ( 감염위험성낮음 ) 에서중등도 ( 감염위험성높음 ), 중증 ( 심각한감염위험성높음 ), 사망에이르기까지의단계를나누고있다. 호중구감소증의정도역시 grade I-Ⅳ로분류될수있으며, 현재적용하는절대호중구수치에따른 grade분류는표에제시된바와같다 (Table 6). Table 6. Diagnosing Standard of Leukopenia and Neutropenia WBC count decrease Neutrophil count Grade (10 9 /L) decrease (/mm 3 ) Ⅰ >1,500 Ⅱ Ⅲ Ⅳ < 이외에연구대상의암진단은 疾病临床诊断和疗效标准, 中国常见恶性肿瘤诊治规范, 实用肿瘤内科学 을비롯하여 CT, MRI 및임상병리학적근거에따라이루어졌고, 결과변수중백혈구감소증치료유효율의판단기준은 中药新药临床研究指导原则, 血液病诊断及疗效标准, 新药西药临床研究指导原则 을바탕으로이루어졌다. (2) 치료개입및대조군 1 치료기간 : 한약 (Traditional herbal medicine, THM) 치료기간은 5일에서 42일까지분포하였으나대부분 2주나 3주로, 평균 일이었다. 2 다른치료의병용 : 양약의병용치료를겸한경우 leucogen 과 batilol병용 (n=3), batilol(n=1), G-CSF(granulocyte colony stimulating factor)(n=3) 을사용하였다. 3 대조군 : 대조군은모두양약치료군이었으며, 지지요법 (supportive treatment) 으로서 leucogen 과 batilol병용 (n=11), leucogen(n=10), batilol(n=5), leucogen, batilol 과 Vt(vitamin) B4 병용 (n=4), leucogen, batilol과 rubidate병용 (n=2), leucogen 과 Vt(Vitamin) B4 병용 (n=1), 치료법으로서 G-CSF (n=5) 등의순으로사용되었다. 3) 결과변수선정된 42 편에서측정된결과변수는유효율 (effective rate)(n=36) 과백혈구수 (WBC count)(n=24) 가대부분이었으며, 이외에사용된결과변수지표로는백혈구감소발생률 (incidence rate of leukemia)(n=3), 호중구수 (neutrophil count)(n=2) 및삶의질을평가하는지표인 KPS(n=2), ECOG(n=2) 를포함하여 CR(curative rate), CD3(cluster of differentiation, CD), CD4, CD8, CD4/8, TR(recovery time of WBC), RS(rate of side effects), RN(incidence rate of neutropenia), BW(body weight) 등이었다. 그중 4 편 52,53,55,56 을제외한연구에서치료군이대조군에비하여통계적유의성에관계없이증상의개선정도가더크다는결과를나타냈다. 3. 개별연구의비뚤림위험선정된 42편의모든연구에대하여 RoB를수행하였다 (Fig. 2, Table 7). 42개의 RCT 연구중오직 7개 (16.7%) 의연구에서치료군과대조군대상자들의무작위배정방법에대해설명하였다. 이중 5개의논문에서난수표의방법을, 1개의연구에서컴퓨터코딩의방법을, 1개의논문에서동전던지기 526

8 김민서 정유진 홍상훈 의방법을이용한단순무작위배정 (simple randomization) 방법을사용하였다. 나머지연구에서는눈가림과정에대한언급이없어해당과정의비뚤림위험은높았다. 연구의참여자와연구자의눈가림에대해서는모든연구에서사용된한약과양약시술이확연히구별되는중재의특성상비뚤림위험이 높다 고판단하였다. 1개의연구에서결측치가있음에도탈락률및탈락의이유에대한설명이없어비뚤림위험이 높다 고판단하였으며, 4개의연구에서탈락률및결측사유에대해명확히제시하여비뚤림이 낮다 평가하였다. 나머지 37개의연구에서는무작위배정시의대상자수와결과값의분석시의대상자수가동일하였기에결측치가없는것으로보여비뚤림평가는 낮다 고할수있으나, 대부분의연구에서참가자흐름 (participant flow) 을제시하지않았기에결측치의여부에대한판단이명확하지못한점이있다. 선택적결과보고에대한비뚤림과관련하여대체적으로결과값을도출하기위한프로토콜자체가언급되지않는논문이대부분이었으나, 사전에정해진평가척도를보고한경우라면 낮은 것으로평가하였다. 모든논문에서결과수치보고가누락되지않았다. Fig. 2. Risk of bias graph on 42 RCTs. Table 7. Summary of Risk of Bias on 42 RCTs Study ID (1) (2) (3) (4) (5) (6) (7) Study ID (1) (2) (3) (4) (5) (6) (7) Cheng (2013) 16 U U H U L L U Wang (2013) 37 L U H U L L U Chu (2016) 17 U U H U L L U Wei (2009) 38 U U H U L L U Du (2014) 18 L U H U L L U Wu (2010) 39 U U H U L L U Feng (2015) 19 U U H U L L U Wu (2013) 40 U U H U L L U Han (2007) 20 U U H U L L U Xie (2010) 41 U U H U L L U Hao (2015) 21 L U H U L L U Xu (2012) 42 L U H U L L U He (2012) 22 U U H U U L U Yu (2011) 43 L L H U L L U Hou (2012) 23 U U H U L L U Zhang (2009) 44 U U H U L L U Jin (2012) 24 U U H U L L U Zhang (2010) 45 U U H U L L U Li M (2008) 25 U U H U L L U Zhou (2017) 46 U U H U L L U Li P (2008) 26 U U H U L L U Liu (2007) 47 U U H U L L U Liu (2008) 27 U U H U L L U Liu (2012) 48 U U H U L L U Liu (2015) 28 U U H U L L U Shi (2014) 49 U U H U L L U Ma (2014) 29 U U H U H L U Wu (2016) 50 U U H U L L U Ni (2010) 30 U U H U L L U Zeng (2010) 51 U U H U L L U Qian (2011) 31 U U H U L L U Li (2014) 52 L U H U L L U Shi (2009) 32 U U H U L L U Zhang (2007) 53 U U H U L L U Tian (2009) 33 U U H U L L U Sun (2009) 54 U U H U L L U Tong (2015) 34 U U H U L L U Zhang (2012) 55 U U H U U L U Wang (2009) 35 U U H U L L U Quo (2007) 56 U U H U L L U Wang (2011) 36 U U H U L L U Yu (2013) 57 L U H U L L U (1) selection bias (random sequence generation), (2) selection bias (allocation concealment), (3) performance bias, (4) detection bias, (5) attrition bias, (6) reporting bias, (7) other bias 527

9 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) 4. 치료결과 1) 정성적분석선정된 42개의 RCTs 연구들은각연구특징에따라분석되었다. 중재와대조군에따라 7개의하위그룹으로나누어연구대상, 중재, 치료방법및기간, 치료결과의효과크기등의상세내용을 Table 8 에정리하였다. ⅰ. THM vs supportive treatment ⅱ. THM + supportive treatment vs supportive treatment ⅲ. THM(powder) vs THM(decoction) vs supportive treatment ⅳ. THM vs G-CSF ⅴ. THM + G-CSF vs G-CSF ⅵ. THM vs THM + G-CSF vs G-CSF ⅶ. THM vs no treatment 변증과한약구성에관한세부내용은 Table 9 에서, 약재사용빈도별분류는 Table 10에서확인할수있다. Table 8. Summary of 42 RCTs Included in This Review Sample size CTh for Study Age (male/female) Cancer both ID (years) INT CON groups Intervention Control THM vs supportive treatment Cheng (2013) (24/16) (22/18) Unspecified DCF, Shengxuebao Heji, Leucogen 20 mg, GP etc. 15 ml, tid, for 14 days tid, PO, for 14 days Chu (2016) () Du (2014) (18/6) Feng (2015) () Han (2007) (26/10) Hao (2015) (16/14) (15/15) He (2012) (14/17) Hou (2012) (64/22) Jin (2012) / (18/12) Li M (2008) (13/17) Yiqi Shengbai 60 () Breast Ca Leucogen 20 mg,, 150 ml, tid, PO, for 1 month bid, for 1 month Jianpi Yiqi Yangxue 24 Colorectal mfolfox6 Fang, 200 ml, bid, (16/8) Ca for 3 weeks Yiqi Shengbai Tang, 30 () Breast Ca FAC 150 ml, bid, for 1 month Fuzheng Guben Tang, 36 (19/17) Unspecified 200 ml, bid, for 21 days Sanhuang Sanxian Lung Ca NP, EP Tang, 300 ml, bid, from 1 day after to 5 days after CTh Guiqi Shengbai Tang, 30 (16/14) Unspecified Unspecified 200 ml, bid, for 2 weeks 61 Unspecified Unspecified (45/16) 30 Unspecified (16/14) Modified Shiqu Dabu Tang, dose unreported, bid, for 20 days Outcome measures WBC, ER, RL WBC, ER, ECOG Leucogen 20 mg, WBC, KPS, tid, PO, for 2 weeks BW, RS, CR Leucogen 20 mg, tid, PO, for 1 month Leucogen 20 mg+ batilol 100 mg, tid, PO, for 21 days Batilol 20 mg+ leucogen 20 mg, tid, PO, from 1 day after to 5 days after CTh Batilol 50 mg+ leucogen 20 mg+ Vit B4 20 mg, tid, for 2 weeks Leucogen 20 mg+ batilol 100 mg, tid, PO, for 20 days Yiqiyangxue, Jianpi Bushen Fang, dose Berbamin hydrochloride unreported, bid, 112 mg, tid, for 15 days for 15 days Jianpi Yishen Tang, 30 (15/15) Unspecified 150 ml, bid, for 21 days Batilol 100 mg, PO, for 21 days WBC, ER, ECOG WBC, ER ER, WBC, NEUT, CR ER ER ER WBC, ER WBC (MD [95% CI]) 1.26 [0.60, 1.92] 1.01 [0.88, 1.14] 0.37 [0.13, 0.61] 0.77 [0.59, 0.95] 1.80 [1.26, 2.34] 0.86 [0.28, 1.44] 1.79 [1.21, 2.37] Effective rate (OR [95% CI]) 3.40 [1.16, 10.00] 3.86 [1.41, 10.57] 2.79 [0.75, 10.33] 7.48 [1.52, 36.78] 0.20 [0.04, 1.02] 3.47 [1.04, 11.56] 3.77 [1.50, 9.43] 7.00 [1.38, 35.48] [2.00, ] 528

10 김민서 정유진 홍상훈 Li P (2008) Unspecified (45/21) (21/13) Liu (2008) () Liu (2015) (42/18) Ma (2014) () Ni 50.08/ (2010) (60/35) Modified Danggui Batilol 50 mg+ Buxue Tang, Dose leucogen 20 mg, tid, unreported, bid, PO, for 30 days for 30 days 90 () Unspecified Shengbai Tang, 150 ml, bid, for 6 days 60 (45/15) 43 () NSCLC DDP+RTh ⅢA or ⅢB () 85 (49/36) Unspecified Qian (2011) Lung Ca/ (20/10) (18/12) gastric Ca Shi (2009) (42/38) EP, TP, CHOP, FOLFOX, etc. Yiqi Shengsui Tang, 200 ml bid, for 3 weeks*2 Yangyin Tiansui Fa, ml, bid, for 3 weeks Shengxue Tang, 150 ml, bid, for 2 weeks Yangxue Shengbai TP Tangjiang, 15 ml, tid, for 21 days Yiqi Shengbai 40 (25/15) Unspecified Tang, unspecified Tian (2009) Unspecified (56/44) (58/42) Tong (2015) (0/34) Wang 54.2/ (2009) (67/43) 34 (0/34) Gynecological Ca CTh () +RTh () course, for 15 days Jiandu Zengxiao Shengbai Tang, 150 ml, bid, for 4 weeks Ganmai Dazao Tang, dose unreported, bid, for 15 days DDP, 100 (55/45) Unspecified Piwei Tang, 150 ml, FAM, EP, bid, for 2 weeks etc. Leucogen 30 mg, tid, PO, for 6 days Leucogen 20 mg+ Inosine 600 mg, tid, PO, for 3 weeks*2 Batilol, course unreported Leucogen 20 mg+ Vit B4 20 mg+ batilol 50 mg, tid, PO, for 2 weeks ER ER ER, CR WBC WBC, ER Leucogen 20 mg, ER, RL, CR, tid, PO, for 21 days KPS, RS Batilol 20 mg, tid, PO, for 15 days Leucogen 20 mg+ batilol 100 mg, tid, PO, for 4 weeks Batilol 20 mg, tid, PO, for 15 days Leucogen 20 mg+ Vit B4 20 mg+ batilol 50 mg, tid, PO, for 2 weeks ER WBC, ER, CR WBC, ER WBC, CR Modified Sancai Batilol 100 mg+ Wang (2011) Fengsui Tang, WBC, ER, Unspecified leucogen 20 mg, (24/21) (23/21) dose unreported, RI, KPS tid, for 14 days bid, for 14 days Shuanghuang WBC, CR, Wang (2013) (45/35) (40/35) Lung Ca NP Leucogen 20 mg, Shengbai Keli, 15 g, NK, tid, PO, for 14 days tid, for 14 days CD3,4,8,4/8 Buxue Shengbai Batilol 50 mg+ Wei (2009) (22/23) (17/17) Unspecified Tang, dose unreported, leucogen 20 mg, ER bid, for 7 days tid, PO, for 7 days Shengbai Tang, Batilol 100 mg+ Wu (2010) (18/12) (17/13) Unspecified dose unspecified, leucogen 20 mg, WBC, ER bid, for 4 weeks tid, for 4 weeks Batilol 50 mg+ Shengbai Tang, Wu (2013) (20/19) (21/18) Unspecified leucogen 20 mg+ RL, ER, 150 ml, bid, Vit B4 20 mg, tid, CR, RI, RS for 8 days for 8 days Xie (2010) Unspecified (34/33) (37/33) Yiqi Wenyang Tang, Leucogen 30 mg, dose unreported, tid, PO, from 48 h bid, from 48 h after after CTh for 3 weeks CTh for 3 weeks ER 0.86 [0.33, 1.39] 2.31 [2.20, 2.42] 0.95 [0.84, 1.06] 0.85 [0.29, 1.41] 1.91 [1.78, 2.04] 0.53 [0.16, 0.90] 0.39 [-0.04, 0.82] 1.50 [1.15, 1.85] 4.78 [1.58, 14.44] 8.00 [4.06, 15.75] 6.51 [1.38, 30.79] [12.23, ] 1.64 [0.53, 5.12] [8.46, ] 4.67 [1.92, 11.35] [2.30, 54.56] 6.45 [1.96, 21.27] 4.90 [1.40, 17.16] 4.26 [0.81, 22.53] [5.37, 55.74] 5.33 [1.46, 19.52] 529

11 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) Xu (2012) (49/37) Yu (2011) (19/13) Zhang (2009) (14/13) Zhang (2010) () 67 Unspecified Unspecified (37/30) Modified Sijunzi and Danggui buxue Tang, dose unreported, bid, for 2 weeks Jianpi Bushen Tang, 30 Colorectal FOLFOX4 course unspecified, (17/13) Ca for 14 days Jiyu Shengbai Tang, 27 (13/14) Unspecified unspecified course, for 4 weeks, Tongbu Sansheng 34 () Unspecified Unspecified Tang, 150 ml, bid, for 2 weeks Modified Shenlingbaizhu San, 100 ml, bid, for 30 days Zhou (2017) Unspecified (24/21) (22/20) THM + supportive treatment vs supportive treatment Liu (2007) (16/4) Liu (2012) (0/16) 20 (18/2) 16 (0/16) Unspecified Gynecological Ca Shi (2014) Unspecified (15/10) (14/11) Yiqi Shengbai Tang, 100 ml, bid+ batilol 40 mg, tid, PO, for 2 weeks Leucogen 20 mg+ Vit B4 20 mg+ creatinine 0.4 g, tid, PO, for 2 weeks Leucogen 20 mg, tid, PO, for 14 days Leucogen 20 mg+ Vt B4 20 mg, tid, PO, for 4 weeks Leucogen 20 mg+ batilol 50 mg, tid, PO, for 2 weeks ER, CR WBC, CD3,4,4/8 ER, KPS, CR, RI WBC, ER, CR WBC, ER 0.80 [0.18, 1.42] 0.73 [0.48, 0.98] 1.44 [0.60, 2.28] Leucogen 20 mg, tid, PO, for 30 days WBC, ER 0.56 [0.05, 1.07] Batilol 50 mg+ Doubled volume of leucogen 20 mg+ Bazhen Tang, bid, rubidate 0.2 g, tid, for 1-3 weeks PO, for 1-3 weeks Yiqi buxue Tang, unspecified course, Batilol 100 mg+ +batilol 100 mg leucogen 20 mg+ +leucogen 20 mg Vit B4 20 mg, tid, +Vit B4 20 mg, PO, for 2 weeks tid, PO, for 2 weeks VDLP, DA, Ganmai Dazao Tang, Wu (2016) (62/43) (30/20) Blood Ca AML, MP, dose unreported, MOPP etc. bid, for 4 weeks THM(powder) vs THM(decoction) vs supportive treatment Guipi Tang Guipi Chaowei, Zeng (2010) (18/ (20/ (18/ Unspecified Yinpian, 150 ml, 12) 10) 12) bid for bid for 4 weeks 4 weeks THM vs G-CSF Buqi Shengbai Tang, Li (2014) (25/20) (27/19) Unspecified Unspecified dose unreported, bid, for 21 days Modified Fuzi Zhang (2007) Lizhong Tang, Unspecified (71/27) (28/14) unspecified course, for 3 weeks THM + G-CSF vs G-CSF Sun (2009) 54 (53.45 / 51.4) 75 (51/24) 73 Unspecified (48/25) Jianpi Yushen Shengbai Tang, 100 ml, bid, for 10 days+g-csf, 150 μg, qd, for 5 days Batilol 40 mg, tid, PO, for 2 weeks WBC, ER 0.34 [-0.22, 0.90] Batilol 20 mg, tid, PO for 4 weeks Batilol 50 mg+ leucogen 20 mg tid, for 4 weeks G-CSF 200 μg, qd, SC, stop if WBC 10.0 G-CSF, 200 μg, qd, SC, for 5 days G-CSF, 150 μg, qd, for 5 days ER ER, TR, CR WBC, ER, RL, RS WBC, ER, TR, KPS WBC, ER, RL, CR, RS ER 0.44 [0.23, 0.65] Powder vs ST 0.35 [-0.29, 0.99] [-1.14, -0.82] 2.39 [1.09, 5.26] 4.14 [1.00, 17.18] [2.10, ] 3.32 [1.08, 10.18] 2.71 [0.97, 7.60] [2.43, 74.87] 3.46 [0.32, 37.47] 2.32 [0.51, 10.54] 6.00 [2.45, 14.68] Powder vs ST 2.36 [0.63, 8.92] 1.63 [0.60, 4.48] 0.92 [0.37, 2.29] RL 530

12 김민서 정유진 홍상훈 Zhang (2012) () 43 () THM vs THM + G-CSF vs G-CSF 20 Quo (2007) (10/ 10) THM vs no treatment Yu (2013) (0/32) 10 (9/ 11) 22 (10/ 12) 32 (0/32) GP, DCF, Unspecified etc. Breast CA, lung CA, AML, lymphoma Breast cancer FAC Shengxue Wan, 6 g, bid, for 10 days+ G-CSF, 200 μg, qd, SC, for 5 days Jianpi Yishen, 250 ml, bid, for 2 weeks Milk Yan Xiao Tang, 175 ml, bid, from 3 days after op for 21 days G-CSF, 200 μg, qd, SC, for 5 days G-CSF, 150 μg, qd, SC, for 7 days - WBC WBC, ER, NEUT, RL, KPS, CR, RS ER, CR, RS 3.48 [3.13, 3.83] THM vs G-CSF [-1.54, 0.38] THM+G-CSF vs G-CSF 1.68 [0.52, 2.84] THM vs G-CSF 0.31 [0.08, 1.11] THM+G-CSF vs G-CSF 3.38 [0.59, 19.16] 3.86 [1.33, 11.16] Study ID : study identification number, INT : intervention group, CON : control group CTh : chemotherapy regimen, administrated to patients in both intervention and control group before and during the clinical tiral; MD : mean difference, Ca : cancer, CI : confidence interval, OR : odds ratio, THM : Traditional herbal medicine, AML : Acute myeloid leukemia, CHOP : cyclophosphamide/vincristine/prednisone/doxorubicin, NP : vinorelbine/cisplatin, FOLFOX : oxaliplatin/5-fu, DA : cytarabine plus daunorubicin, DCF : docetaxel/cisplatin/5-fluorouracil, DDP : cisplatin, TP : docetaxel/cisplatin, FAM : 5-fluorouracil/adriamycin/mitomycin, FAC : 5-fluorouracil(5-FU)/adriamycin(doxorubicin) /cyclophosphamide, EP : etoposide/carboplatinum or cisplatin, CTX : cyclophosphamide, GP : gemcitabine/cisplatin, MOPP : mustargen/oncovin/provarbazine/prednisone, MP : melphalan/prednisolone, VDLP : vincristine/daunorubicin /L-asparaginase/prednisone, qd : once daily, bid : twice daily, tid : three times daily, IV : intravenous drip, SC : subcutaneous injection, PO : oral, BW : body weight, ER : effective rate, NEUT : neutrophil count, RL : incidence rate of leucopenia, RN : incidence rate of neutropenia, RS : rate of side effects, TR : recovery time of WBC, KPS : Karnofsky score, CR : curative rate, G-CSF : granulocyte colony stimulating factor, : no available data, *P<0.05 Table 9. Pattern Identifications and THM Formulas Used in 42 RCTs Study Herbal medicine Form Pattern Herbal formulas ID THM vs supportive treatment Cheng 16 (2013) Chu 17 (2016) Shengxuebao Heji ( 生血宝合剂 ) Syrup Yiqi Shengbai Tang ( 益氣升白汤 ) ( 虛勞 ) ( 虛勞 ), blood-deficiency ( 血虛 ) spleen-kidney deficiency ( 脾腎虧虛 ), qi-blood deficiency ( 氣血不足 ), Pleuropterus multiflorus ( 何首乌 ), Ligustrum lucidum ( 女貞子 ), Mori Fructus ( 桑椹子 ), Eclipta prostrata ( 旱蓮草 ), Paeoniae Radix Alba ( 白芍藥 ), Astragali Radix ( 黃芪 ), Cibotium barometz ( 狗脊 ) Astragali Radix ( 生黃芪 ), Rehmanniae RaRehmanniae Radix Preparatdix Preparat ( 熟地黃 ), Atractylodis Rhizoma Alba ( 白朮 ), Codonopsis Pilosulae ( 黨蔘 ), Ligustri Lucidi Fructus ( 女貞子 ), Angelicae Gigantis Radix ( 當歸 ), Polygonati Rhizoma ( 黃精 ), Dioscoreae Rhizoma ( 山藥 ), Cuscutae Semen ( 菟絲子 ), Spatholobi Caulis ( 鷄血藤 ), Citri Reticulatae Pericarpium ( 陳皮 ), Lycii Fructus ( 枸杞子 ) 531

13 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) Du 18 (2014) Feng 19 (2015) Jianpi Yiqi Yangxue Fang ( 健脾益氣养血方 ) Formula Yiqi Shengbai Tang ( 益氣升白汤 ) Codonopsis Pilosulae Radix ( 黨蔘 ), Angelicae Gigantis Radix ( 當歸 ), Paeoniae Radix Rubra ( 赤芍藥 ), Notoginseng Radix Spleen and kidney ( 参三七 ), Astragali Radix ( 生黃芪 ), Chinemydis Plastrum deficiency ( 脾腎虧虛 ), ( 炙龟甲 ), Hominis Placenta ( 紫河车 ), Asini Gelatinum qi-blood deficiency ( 阿胶 ), Rehmanniae Radix ( 熟地黃 ), Amomi Fuctus ( 阳春 ( 氣血虧耗 ) 砂 ), Citri Pericarpium ( 陈皮 ), Pinelliae Rhizoma ( 法制半夏 ), Crataegii Fructus ( 焦山査 ), Massa Medicata Fermentata ( 焦六神曲 ), Hordei Fructus Germiniatus ( 炒麥芽 ) ( 虛勞 ), blood-deficiency ( 血虛 ) spleen-kidney deficiency ( 脾腎虧虛 ), qi-blood deficiency ( 氣血不足 ) Han 20 Fuzheng Guben Tang (2007) ( 自拟扶正固本汤 ) ( 虛勞 ), Hao 21 (2015) He 22 (2012) Hou 23 (2012) Jin 24 (2012) Sanhuang Sanxian Tang ( 三黄三仙汤 ) Guiqi Shengbai Tang ( 归芪升白汤 ) Modified Shiqu Dabu Tang ( 十全大补汤加减 ) Yiqi Yangxue, Jianpi Bushen Fang ( 益氣养血, 健脾补肾方 ) Astragali Radix ( 生黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Dioscoreae Rhizoma ( 山藥 ), Atractylodis Rhizoma Alba ( 白朮 ), Angelicae Gigantis Radix ( 當歸 ), Polygonati Rhizoma ( 黃精 ), Spatholobi Caulis ( 鷄血藤 ), Cuscutae Semen ( 菟絲子 ), Lycii Fructus ( 枸杞子 ), Ligustri Lucidi Fructus ( 女貞子 ), Rehmanniae Radix Preparat ( 熟地黃 ), Citri Reticulatae Pericarpium ( 陳皮 ) Pseudostellariae Radix ( 太子參 ), Rehmanniae Radix et Rhizoma Preparata ( 生熟地黃 ), Lycii Fructus ( 枸杞子 ), Cistanches Herba ( 肉蓯蓉 ), Morindae Radix ( 巴戟天 ), Polygoni Multiflori Radix ( 何首烏 ), Ligustri Lucidi Fructus ( 女貞子 ), Corni Fructus ( 山萸肉 ), Cuscutae Semen ( 菟絲子 ), blood-deficiency ( 血虛 ) ( 虛勞 ), blood-deficiency ( 血虛 ) Formula ( 虛勞 ), qi-blood deficiency ( 氣血兩虛 ) ( 虛勞 ) ( 虛勞 ) Atractylodis Rhizoma Alba ( 白朮 ), Polygonati Rhizoma ( 黃精 ), Angelicae Gigantis Radix ( 當歸 ), Manititis Squama ( 炮山甲 ), Paeoniae Radix Alba ( 白芍藥 ), Asini Gelatinum ( 阿膠 ), Cimicifugae Rhizoma ( 升麻 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 生黃芪 ), Scutellariae Radix ( 黄芩 ), Polygonati Rhizoma ( 黃精 ), Agrimoniae Herba ( 仙鶴草 ), Curculiginis Rhizoma ( 仙茅 ), Paeoniae Radix Alba ( 白芍藥 ),Angelicae Gigantis Radix ( 當歸 ), Spatholobi Caulis ( 鷄血藤 ), Ligustri Lucidi Fructus ( 女貞子 ), Epimedi Herba ( 淫羊藿 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Spatholobi Caulis ( 鷄血藤 ), Ligustri Lucidi Fructus ( 女貞子 ), Angelicae Gigantis Radix ( 當歸 ), Atractylodis Rhizoma Alba ( 白朮 ), Asini Gelatinum ( 阿膠 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 黃芪 ), Rehmanniae Radix Preparat ( 熟地黃 ), Ginseng Radix ( 人蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Polia Sclerotium ( 茯笭 ), Paeoniae Radix Alba ( 白芍藥 ), Spatholobi Caulis ( 鷄血藤 ), Cinnamomi Cortex Spissus ( 肉桂 ), Cnidii Rhizoma ( 川芎 ), Angelicae Gigantis Radix ( 當歸 ), Asini Gelatinum ( 阿膠 ; 烊化 ), Glycyrrhizae Radix Praeparata ( 炙甘草 ) Astragali Radix ( 黃芪 ), Pseudostellariae Radix ( 太子參 ), Atractylodis Rhizoma Alba ( 白朮 ), Polia Sclerotium ( 茯笭 ), Rehmanniae Radix Preparat ( 熟地黃 ), Angelicae Gigantis Radix ( 當歸 ), Ligustri Lucidi Fructus ( 女貞子 ), Corni Fructus ( 山茱萸 ), Spatholobi Caulis ( 鷄血藤 ), Cuscutae Semen ( 菟絲子 ), Epimedi Herba ( 仙靈脾 ), Lycii Fructus ( 枸杞子 ), Citri Reticulatae Pericarpium ( 陳皮 ) 532

14 김민서 정유진 홍상훈 Li M 25 (2008) Li P 26 (2008) Liu 27 (2008) Liu 28 (2015) Ma 29 (2014) Ni 30 (2010) Qian 31 (2011) Jianpi Yishen Tang ( 健脾益肾汤 ) Modified Danggui Buxue Tang ( 当归补血汤加味 ) Shengbai Tang ( 升白汤 ) Yiqi Shengsui Tang ( 益氣生髓汤 ) Yangyin Tiansui Fa ( 养阴填髓法 ) Shengxue Tang ( 升血汤 ) Yangxue Shengbai Tangjiang ( 养血生白糖浆 ) Syrup ( 虛勞 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Polia Sclerotium ( 茯笭 ), Spatholobi Caulis ( 鷄血藤 ), Psoraleae Fructus ( 补骨脂 ), Cuscutae Semen ( 菟絲子 ), Ligustri Lucidi Fructus ( 女貞子 ), Epimedi Herba ( 仙靈脾 ), Lycii Fructus ( 枸杞子 ), Theae Semen Germinatus ( 穀芽 ), Hordei Fructus Germiniatus ( 麥芽 ), Galli Stomachichum Corium ( 鷄內金 ), Dioscoreae Rhizoma ( 山藥 ), Coicis Semen ( 薏苡仁 ), Citri Reticulatae Pericarpium ( 陳皮 ) Astragali Radix ( 黃芪 ), Spatholobi Caulis ( 鷄血藤 ), Codonopsis Qi-blood deficiency Pilosulae ( 黨蔘 ), Angelicae Gigantis Radix ( 當歸 ), Atractylodis ( 氣血兩虛 ), Rhizoma Alba ( 白朮 ), Polygoni Multiflori Radix ( 何首烏 ), spleen-kidney Crataegii Fructus ( 山楂 ), Polygonati Rhizoma ( 黄精 ), Asini deficiency ( 脾腎兩虛 ) Gelatinum ( 阿膠 ), Epimedi Herba ( 淫羊藿 ), Zizyphi Fructus ( 大棗 ) Angelicae Gigantis Radix ( 當歸 ), Astragali Radix ( 黃芪 ), Spleen-kidney Spatholobi Caulis ( 鷄血藤 ), Pseudostellariae Radix ( 太子 deficiency ( 脾腎兩虛 ), 参 ), Manititis Squama ( 炮山甲 ), Paeoniae Radix Alba ( 炒 qi-blood deficiency 白芍 ), Corni Fructus ( 山茱萸 ), Psoraleae Fructus ( 补骨脂 ), ( 氣血兩虛 ) Ligustri Lucidi Fructus ( 女貞子 ), Asini Gelatinum ( 阿膠 ), Pyrrosiae Folium ( 石葦 ), Glycyrrhizae Radix ( 甘草 ) Spleen-kidney deficiency ( 脾腎虧虛 ) ( 虛勞 ) Astragali Radix ( 黃芪 ), Ginseng Radix ( 红参 ), Paeoniae Radix Alba ( 白芍藥 ), Polia Sclerotium ( 茯笭 ), Glycyrrhizae Radix ( 甘草 ), Atractylodis Rhizoma Alba ( 白朮 ), Cervi Cornus Colla ( 鹿角膠 ), Asini Gelatinum ( 阿膠 ), Rehmanniae Radix Preparat ( 熟地黃 ), Angelicae Gigantis Radix ( 當歸 ), Cnidii Rhizoma ( 川芎 ), Jujubae Fructus ( 红枣 ), Zingiberis Rhizoma Recens ( 生薑 ) Polygonati Rhizoma ( 黃精 ), Codonopsis Pilosulae ( 黨蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Polia Sclerotium ( 茯笭 ), Rehmanniae Radix et Rhizoma Preparata ( 生熟地黃 ), Ligustri Lucidi Fructus ( 女貞子 ), Lycii Fructus ( 枸杞子 ), Cuscutae Semen ( 菟絲子 ), Angelicae Gigantis Radix ( 當歸 ), Spatholobi Caulis ( 鷄血藤 ), Polygoni Multiflori Radix ( 何首烏 ), Glycyrrhizae Radix Praeparata ( 炙甘草 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Polia Sclerotium ( 茯笭 ), Dioscoreae Rhizoma ( 山藥 ), Citri Reticulatae Pericarpium ( 陳皮 ), Galli Spleen-kidney Stomachichum Corium ( 鷄內金 ), Ligustrum lucidum ( 女貞 deficiency ( 脾腎两虚 ) 子 ), Eclipta prostrata ( 旱蓮草 ), Psoraleae Fructus ( 补骨 qi-blood deficiency 脂 ), Drynariae Rhizoma ( 骨碎補 ), Cervi Cornus Colla ( 鹿 ( 氣血不足 ) 角膠 ), Asini Gelatinum ( 阿膠 ; 烊化 ), Lycii Fructus ( 枸杞子 ), Spatholobi Caulis ( 鷄血藤 ), Angelicae Gigantis Radix ( 當歸 ), Paeoniae Radix Rubra ( 赤芍藥 ), Glycyrrhizae Radix Praeparata ( 炙甘草 ), Zizyphi Fructus ( 大棗 ) ( 虛勞, 虚损 ) qi-yin deficiency ( 氣陰兩虛 ) Codonopsis Pilosulae ( 黨蔘 ), Astragali Radix ( 炙黃芪 ), Rehmanniae Radix Preparat ( 熟地黃 ), Ligustri Lucidi Fructus ( 女貞子 ), Lycii Fructus ( 枸杞子 ), Atractylodis Rhizoma Alba ( 炒白朮 ), Polygoni Multiflori Radix ( 何首烏 ) 533

15 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) Shi 32 Yiqi Shengbai Tang (2009) ( 自拟益氣升白汤 ) Tian 33 (2009) Tong 34 (2015) Wang 35 (2009) Wang 36 (2011) Wang 37 (2013) Wei 38 (2009) Wu 39 (2010) Jiandu Zengxiao Shengbai Tang ( 减毒增效升白汤 ) Ganmai Dazao Tang ( 甘麦大枣汤 ) Piwei Tang ( 脾胃汤 ) Modified Sancai Fengsui Tang ( 加味三才封髓汤 ) Shuanghuang Shengbai Keli ( 双黄升白颗粒 ) Spleen-kidney deficiency ( 脾腎受损 ), qi-blood deficiency ( 氣血虧虛 ) Codonopsis Pilosulae ( 黨蔘 ), Astragali Radix ( 黃芪 ), Spatholobi Caulis ( 鷄血藤 ), Epimedi Herba ( 淫羊藿 ), Cervi Cornus Colla ( 鹿角膠 ), Angelicae Gigantis Radix ( 當歸 ), Pulvis Aconiti Tuberis Purificatum ( 附子 ), Lycii Fructus ( 枸杞子 ), Cinnamomi Cortex Spissus ( 肉桂 ), Zizyphi Fructus ( 大棗 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Atractylodis Qi deficiency ( 中氣虚 ), Rhizoma Alba ( 白朮 ), Psoraleae Fructus ( 补骨脂 ), Ligustri blood deficiency ( 血虚 ) Lucidi Fructus ( 女貞子 ), Spatholobi Caulis ( 鷄血藤 ), Asini Gelatinum ( 阿膠 ) etc. (total 13) Granule Buxue Shengbai Tang ( 补血生白汤 ) Shengbai Tang ( 升白汤 ) Qi-yin deficiency ( 氣阴两虚 ), spleen health loss ( 脾失键运 ) Glycyrrhizae Radix Praeparata ( 炙甘草 ),Tritici Cimmatri Semen ( 浮小麦 ), Zizyphi Fructus ( 大棗 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Coicis Semen ( 薏苡仁 ), Angelicae Gigantis Radix ( 當歸 ), Polygoni Multiflori Radix ( 何首烏 ), Amomi Rotundus Fructus ( 白 Spleen-stomach 荳蔲 ), Atractylodis Rhizoma Alba ( 白朮 ), Cyperi Rhizoma weakness ( 脾胃虚弱 ) ( 香附子 ), Citri Reticulatae Pericarpium ( 陳皮 ), Polia Sclerotium ( 茯笭 ), Pinelliae Rhizoma ( 半夏 ), Amomi Fuctus ( 砂仁 ), Zingiberis Rhizoma Recens ( 生薑 ) Qi-yin deficiency ( 氣阴两虛 ) or blood deficiency ( 血虧 ) Jing-qi deficiency ( 精氣虧虛 ) ( 虚劳 ), spleen & kidney weakness ( 脾肾兩虚 ) Ginseng Radix ( 人蔘 ), Asparagi Radix ( 天門冬 ), Rehmanniae Radix Preparat ( 熟地黃 ), Phellodendri Cortex ( 黄柏 ), Amomi Fuctus ( 砂仁 ), Astragali Radix ( 黃芪 ), Glehniae Radix ( 北沙蔘 ), Cistanches Herba ( 肉蓯蓉 ), Angelicae Gigantis Radix ( 當歸 ), Spatholobi Caulis ( 鷄血藤 ), Schizandrae Fructus ( 五味子 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 生黃芪 ), Polygonati Rhizoma ( 黃精 ), Ligustri Lucidi Fructus ( 女貞子 ), Trichosanthis Radix ( 天花粉 ), Drynariae Rhizoma ( 骨碎補 ) etc. Astragali Radix ( 黃芪 ), Spatholobi Caulis ( 鷄血藤 ), Angelicae Gigantis Radix ( 當歸 ), Asini Gelatinum ( 阿膠 ), Ligustri Lucidi Fructus ( 女貞子 ), Corni Fructus ( 山萸肉 ), Codonopsis Pilosulae ( 黨蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Cnidii Rhizoma ( 川芎 ), Crataegii Fructus ( 山楂 ), Zizyphi Fructus ( 大棗 ) Qi-blood deficiency Spatholobi Caulis ( 鷄血藤 ), Adenophorae Radix ( 沙蔘 ), Asparagi ( 氣血虚弱 ), Radix ( 天門冬 ), Polygonati Rhizoma ( 黃精 ), Pseudostellariae spleen-stomach Radix ( 太子参 ), Astragali Radix ( 黃芪 ), Polygoni Multiflori deficienty ( 脾胃失调 ), Radix ( 何首烏 ), Lycii Fructus ( 枸杞子 ), Rehmanniae Radix liver-kidney ( 生地黃 ), Atractylodis Rhizoma Alba ( 白朮 ), Oldenlandiae deficiency ( 肝肾虧损 ), Diffusae Herba ( 白花蛇舌草 ), Lonicerae Flos ( 金银花 ), Citri body fluid deficiency Reticulatae Pericarpium ( 陳皮 ), Angelicae Gigantis Radix ( 阴津损伤 ) ( 當歸 ), Zizyphi Fructus ( 大棗 ) 534

16 김민서 정유진 홍상훈 Wu 40 (2013) Xie 41 (2010) Xu 42 (2012) Yu 43 (2011) Zhang 44 (2009) Zhang 45 (2010) Zhou 46 (2017) Shengbai Tang ( 升白汤 ) Yiqi Wenyang Tang ( 益氣温阳汤 ) Modified Sijunzi and Dangguibuxue Tang ( 四君子汤与當歸补血汤加味 ) Jianpi Bushen Tang ( 健脾补肾方 ) Jiyu Shengbai Tang ( 鲫鱼升白汤 ) Tongbu Sansheng Tang ( 通补三升汤 ) Modified Shenlingbaizhu San ( 参苓白术散加味 ) Powder Astragali Radix ( 黃芪 ), Pseudostellariae Radix ( 太子参 ), Atractylodis Rhizoma Alba ( 炒白朮 ), Polia Sclerotium ( 茯 Qi-blood-yin-yang 笭 ), Paeoniae Radix Alba ( 白芍藥 ), Corni Fructus ( 山茱 deficiency 萸 ), Psoraleae Fructus ( 补骨脂 ), Ligustri Lucidi Fructus ( 氣血阴阳俱虚 ), ( 女貞子 ), Lycii Fructus ( 枸杞子 ), Asini Gelatinum ( 阿膠 ), spleen-kidney Polygonati Rhizoma ( 黃精 ), Angelicae Gigantis Radix ( 當 deficiency ( 脾肾虧虚 ) 歸 ), Spatholobi Caulis ( 鷄血藤 ), Hominis Placenta ( 紫河車 ), Cuscutae Semen ( 菟絲子 ), Pyrrosiae Folium ( 石葦 ), Manititis Squama ( 炮穿山甲 ), Glycyrrhizae Radix ( 甘草 ) Qi-blood deficiency ( 氣血虧损 ), spleen-stomach disharmony ( 脾胃不和 ), deficiency of spleen-yang and kidney-yang ( 脾肾阳虚 ) Astragali Radix ( 黃芪 ), Ginseng Radix ( 人蔘 ), Polia Sclerotium ( 茯笭 ), Atractylodis Rhizoma Alba ( 白朮 ), Citri Reticulatae Pericarpium ( 陳皮 ), Pinelliae Rhizoma ( 半夏 ), Cinnamomi Cortex Spissus ( 肉桂 ), Zingiberis Rhizoma Siccus ( 乾薑 ), Pogostemi Herba ( 藿香 ), Liriopis Tuber ( 麥門冬 ), Epimedi Herba ( 淫羊藿 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 黃芪 ), Angelicae Gigantis Radix ( 當歸 ), Spleen & kidney Codonopsis Pilosulae ( 黨蔘 ), Polia Sclerotium ( 茯笭 ), deficiency ( 脾肾受损 ), Atractylodis Rhizoma Alba ( 白朮 ), Ligustri Lucidi Fructus qi-blood deficiency ( 女貞子 ), Dioscoreae Rhizoma ( 山藥 ), Corni Fructus ( 山 ( 氣血虧虚 ) 茱萸 ), Coicis Semen ( 薏苡仁 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 生黃芪 ), Pseudostellariae Radix ( 太子参 ), Spleen deficiency ( 脾虚 ), qi-blood deficiency ( 氣血不足 ) Qi-blood deficiency ( 氣血两虚 ), kidney deficiency ( 肾虚 ) ( 虚劳 ) Blood deficiency ( 血虚 ), consumptive disease ( 虚劳 ) THM + supportive treatment vs supportive treatment Liu 47 (2007) Yiqi Shengbai Tang ( 益氣升白汤 ) ( 虚劳 ) Codonopsis Pilosulae( 黨蔘 ), Polia Sclerotium ( 茯笭 ), Atractylodis Rhizoma Alba ( 炒白朮 ), Lycii Fructus ( 枸杞子 ), Ligustri Lucidi Fructus ( 女貞子 ), Spatholobi Caulis ( 鷄血藤 ), Corni Fructus ( 山茱肉 ), Psoraleae Fructus ( 补骨脂 ), Cuscutae Semen ( 菟絲子 ), Jiao Sanxian ( 焦三仙 ), Galli Stomachichum Corium ( 鷄內金 ), Amomi Fuctus ( 砂仁 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Angelicae Gigantis Radix ( 當歸 ), Ligustri Lucidi Fructus ( 女貞子 ), Lycii Fructus ( 枸杞子 ), Amomi Fuctus ( 砂仁 ), Citri Reticulatae Pericarpium ( 陳皮 ), Carassii Caro ( 鲫鱼 ), meat (a dietary regime) Astragali Radix ( 黃芪 ), Rubiae Radix ( 茜根 ), Rehmanniae Radix Preparat ( 熟地黃 ), Corni Fructus ( 山茱萸 ), Angelicae Gigantis Radix ( 當歸 ), Polygonati Rhizoma ( 黃精 ), Ginseng Radix ( 红参 ), Ganodermae Polyporus ( 靈芝 ), Cervi Cornus Colla ( 鹿角膠 ), Manititis Squama ( 穿山甲 ), Galli Stomachichum Corium ( 鷄內金 ) Ginseng Radix ( 人蔘 ), Dolichoris Semen ( 白扁豆 ), Atractylodis Rhizoma Alba ( 白朮 ), Polia Sclerotium ( 茯笭 ), Dioscoreae Rhizoma ( 山藥 ), Nelumbinis Semen ( 蓮子肉 ), Platycodi Radix ( 桔梗 ), Coicis Semen ( 薏苡仁 ), Amomi Fuctus ( 砂仁 ), Astragali Radix ( 黃芪 ), Ligustri Lucidi Fructus ( 女貞子 ), Lycii Fructus ( 枸杞子 ), Glycyrrhizae Radix ( 甘草 ) Astragali Radix ( 黃芪 ), Codonopsis Pilosulae ( 黨蔘 ), Angelicae Gigantis Radix ( 當歸 ), Lycii Fructus ( 枸杞子 ), Polygonati Rhizoma ( 黃精 ), AuriculariaePolyporus ( 黑木耳 ), Zingiberis Rhizoma Recens ( 生薑 ) 535

17 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) Liu 48 (2012) Shi 49 (2014) Wu 50 Zeng 51 (2010) Doubled volume of Bazhen Tang ( 八珍汤的配方 ) Yiqi buxue Tang ( 益氣补血中药治疗 ) Guipi Tang Chaowei Yinpian ( 归脾汤超微饮片 ) Submicron powder Glycyrrhizae Radix ( 甘草 ), Angelicae Gigantis Radix ( 當歸 ), Lycii Fructus ( 枸杞子 ),Asini Gelatinum ( 阿膠 ), Atractylodis Injured qi ( 伤氣 ), Rhizoma Alba ( 白朮 ), Paeoniae Radix Alba ( 白芍藥 ), Dioscoreae consumed jing ( 耗精 ), Rhizoma ( 山藥 ), Codonopsis Pilosulae ( 黨蔘 ), Astragali injured blood ( 损血 ) Radix ( 黃芪 ), Rehmanniae Radix Preparat ( 熟地黃 ), Polygoni Cuspidati Rhizoma ( 虎杖根 ), Spatholobi Caulis ( 鷄血藤 ) Qi-blood weakness ( 氣血两虚 ), spleen-kidney deficiency ( 脾肾不足 ) ( 虚劳 ), blood deficiency ( 血虚 ) Ginseng Radix ( 红参 ), Astragali Radix ( 黃芪 ),Rehmanniae Radix ( 生地黄 ), Atractylodis Rhizoma Alba ( 白朮 ), Paeoniae Radix Alba ( 白芍藥 ), Angelicae Gigantis Radix ( 當歸 ), Dioscoreae Rhizoma ( 山藥 ), Salviae Miltiorrhizae Radix ( 丹蔘 ) Ganmai Dazao Tang Herbal Toxicity ( 藥毒 ) Glycyrrhizae Radix Praeparata ( 炙甘草 ), Tritici Cimmatri (2016) ( 甘麦大枣汤 ) Semen ( 浮小麦 ), Zizyphi Fructus ( 大棗 ) THM (powder) vs THM (decoction) vs supportive treatment Astragali Radix ( 黃芪 ), Ginseng Radix ( 人蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Angelicae Gigantis Radix ( 當歸 ), Polia Sclerotium ( 茯笭 ), Glycyrrhizae Radix ( 甘草 ), Aucklandiae THM vs G-CSF Li 52 (2014) Zhang 53 (2007) Buqi Shengbai Tang ( 补氣生白汤 ) Modified Fuzi Lizhong Tang ( 加味附子理中汤 ) THM + G-CSF vs G-CSF Sun 54 (2009) Zhang 55 (2012) Jianpi Yushen Shengbai Tang ( 健脾益肾升白汤 ) Shengxue Wan ( 升血丸 ) Pill THM vs THM+G-CSF vs G-CSF Qi-blood deficienty ( 氣血虧虚 ), consumptive disease ( 虚劳 ) Spleen yang-kidney yang deficiency ( 脾肾阳虚 ) Spleen yang-kidney yang deficiency ( 脾肾虧虚 ) Radix ( 廣木香 ), Longanae Arillus ( 龍眼肉 ), Zizyphi Spinosae Semen ( 酸枣仁 ), Polygalae Radix ( 远志 ), Zizyphi Fructus ( 大棗 ), Zingiberis Rhizoma Recens ( 生薑 ) Codonopsis Pilosulae ( 黨蔘 ), Astragali Radix ( 黃芪 ), Atractylodis Rhizoma Alba ( 炒白朮 ), Polia Sclerotium ( 茯笭 ), Angelicae Gigantis Radix ( 當歸 ), Rehmanniae Radix Preparat ( 熟地黃 ), Dioscoreae Rhizoma ( 山藥 ), Lycii Fructus ( 枸杞子 ), Aucklandiae Radix ( 木香 ), Zizyphi Fructus ( 大棗 ), Glycyrrhizae Radix Praeparata ( 炙甘草 ) Pulvis Aconiti Tuberis Purificatum ( 附子 ), Zingiberis Rhizoma Siccus ( 乾薑 ), Atractylodis Rhizoma Alba ( 白朮 ), Glycyrrhizae Radix Praeparata ( 炙甘草 ), Codonopsis Pilosulae ( 黨蔘 ), Ligustri Lucidi Fructus ( 女貞子 ), Cuscutae Semen ( 菟絲子 ), Amomi Fuctus ( 砂仁 ), Hepiali Vermis ( 冬虫夏草 ) Astragali Radix ( 生黃芪 ), Coicis Semen ( 生薏苡仁 ), Phaseoli Semen ( 赤小豆 ), Jujubae Fructus ( 红枣 ), Polia Sclerotium ( 茯笭 ), Angelicae Gigantis Radix ( 當歸 ), Spatholobi Caulis ( 鷄血藤 ), Psoraleae Fructus ( 补骨脂 ), Atractylodis Rhizoma Alba ( 白朮 ), Ligustri Lucidi Fructus ( 女貞子 ), Ginseng Radix ( 人蔘 ), Glycyrrhizae Radix Praeparata ( 炙甘草 ), Atractylodis Rhizoma Alba ( 白朮 ), Curculiginis Rhizoma ( 仙茅 ), Epimedi Herba ( 仙靈脾 ) Astragali Radix ( 黃芪 ), Angelicae Gigantis Radix ( 當歸 ), Polygonati Rhizoma ( 黃精 ), Corni Fructus ( 山茱萸 ), Lycii ( 虚劳 ), Fructus ( 枸杞子 ), Ligustri Lucidi Fructus ( 女貞子 ), Chinemydis spleen-kidney Gelatina ( 龜板膠 ), Galli Stomachichum Corium ( 鷄內金 ), deficiency ( 脾肾两虚 ), Amomi Fuctus ( 砂仁 ), Jiao Sanxian ( 焦三仙 ), Ponciri Fructus qi-blood deficiency Pericarpium ( 枳殼 ), Aucklandiae Radix ( 廣木香 ), Forsythiae ( 氣血不足 ), Fructus ( 連翹 ) 536

18 김민서 정유진 홍상훈 Quo 56 (2007) Jianpi Yishen Tang ( 健脾益肾方 ) THM vs no treatment Yu 57 (2013) Spleen-kidney deficiency ( 脾肾虚损 ) Codonopsis Pilosulae ( 黨蔘 )(or Panaciis Quinquefolii Radix ( 西洋蔘 ), Atractylodis Rhizoma Alba ( 白朮 ), Astragali Radix ( 黃芪 ), Angelicae Gigantis Radix ( 當歸 ), Spatholobi Caulis ( 鷄血藤 ), Polygonati Rhizoma ( 黃精 ), Lycii Fructus ( 枸杞子 ), Cuscutae Semen ( 菟絲子 ), Coicis Semen ( 薏苡仁 ), Forsythiae Fructus ( 連翹 ), Saposhnikovia Radix ( 防風 ), Polyporus ( 猪苓 ), Galli Stomachichum Corium ( 鷄內金 ), Amomi Fuctus ( 砂仁 ), Lycopi Herba ( 澤蘭 ), Salviae Miltiorrhizae Radix ( 丹蔘 ), Raphani Semen ( 炒萊菔子 ), Rehmanniae Radix ( 生地 ), Theae Semen Germinatus ( 炒穀芽 ), Hordei Fructus Germiniatus ( 炒麥芽 ), Glycyrrhizae Radix ( 甘草 ) Lycii Fructus ( 枸杞子 ), Ligustri Lucidi Fructus ( 女貞子 ), Injured body fluid-qi Glycyrrhizae Radix ( 甘草 ), Cuscutae Semen ( 菟絲子 ), Milk Yan Xiao Tang ( 伤津耗氣 ), Scrophulariae Radix ( 玄蔘 ), Polygonati Rhizoma ( 黃精 ), ( 乳岩消湯 ) stasis of blood and Polia Sclerotium ( 茯笭 ), Zedoariae Rhizoma ( 莪朮 ), Astragali phelgm ( 久病则致瘀生痰 ) Radix ( 黃芪 ), Coicis Semen ( 薏苡仁 ), Codonopsis Pilosulae ( 黨蔘 ), Oldenlandiae Diffusae Herba ( 白花蛇舌草 ) Jiao Sanxian ( 焦三仙 ) : Jiao Sanxian 은학명이아닌중의어표기로, 山楂, 神曲, 麦芽를볶은것을의미한다. Table 10. Frequency of Herbal Medicine Frequency Herbal medicine (frequency) >26 Astragali Radix ( 黃芪 ) (37), Angelicae Gigantis Radix ( 當歸 ) (30), Atractylodis Rhizoma Alba ( 白朮 ) (29) Codonopsis Pilosulae ( 黨蔘 ) (22), Glycyrrhizae Radix ( 甘草 ) (22), Ligustri Lucidi Fructus ( 女貞子 ) (22), Spatholobi Caulis ( 鷄血藤 ) (21) Lycii Fructus ( 枸杞子 ) (20), Polia Sclerotium ( 茯笭 ) (16), Polygonati Rhizoma ( 黃精 ) (14), Asini Gelatinum ( 阿膠 ) (12), Cuscutae Semen ( 菟絲子 ) (11) Ginseng Radix ( 人蔘 / 红参 ) (10), Rehmanniae Radix Preparat ( 熟地黃 ) (10), Amomi Fuctus ( 砂仁 ) (9), Citri Reticulatae Pericarpium ( 陳皮 ) (9), Corni Fructus ( 山萸肉 ) (9), Dioscoreae Rhizoma ( 山藥 ) (9), Paeoniae Radix 6-10 Alba ( 白芍藥 ) (9), Zizyphi Fructus ( 大棗 ) (9), Coicis Semen ( 薏苡仁 ) (7), Epimedi Herba ( 仙靈脾 / 淫羊藿 ) (7), Psoraleae Fructus ( 补骨脂 ) (7), Galli Stomachichum Corium ( 鷄內金 ) (6), Polygoni Multiflori Radix ( 何首烏 ) (6), Pseudostellariae Radix ( 太子参 ) (6) Cervi Cornus Colla ( 鹿角膠 ) (4), Manititis Squama ( 炮山甲 ) (4), Zingiberis Rhizoma Recens ( 生薑 ) (4), Aucklandiae Radix (( 廣 ) 木香 ) (3), Cinnamomi Cnidii Rhizoma ( 川芎 ) (3), Cortex Spissus ( 肉桂 ) (3), Crataegii Fructus ( 山楂 ) (3), Hordei Fructus Germiniatus ( 麥芽 ) (3), Pinelliae Rhizoma ( 半夏 ) (3), Rehmanniae Radix ( 生地黃 ) (3), Asparagi Radix ( 天門冬 ) (2), Cistanches Herba ( 肉蓯蓉 ) (2), Curculiginis Rhizoma ( 仙茅 ) (2), 2-5 Eclipta prostrata ( 旱蓮草 ) (2), Forsythiae Fructus ( 連翹 ) (2), Hominis Placenta ( 紫河車 ) (2), Jiao Sanxian ( 焦三仙 ) (2), Jujubae Fructus ( 红枣 ) (2), Oldenlandiae Diffusae Herba ( 白花蛇舌草 ) (2), Paeoniae Radix Rubra ( 赤芍藥 ) (2), Pulvis Aconiti Tuberis Purificatum ( 附子 ) (2), Pyrrosiae Folium ( 石葦 ) (2), Rehmanniae Radix et Rhizoma Preparata ( 生熟地黃 ) (2), Salviae Miltiorrhizae Radix ( 丹蔘 ) (2), Theae Semen Germinatus ( 穀芽 ) (2), Tritici Cimmatri Semen ( 浮小麦 ) (2), Zingiberis Rhizoma Siccus ( 乾薑 ) (2) Adenophorae Radix ( 沙蔘 ), Agrimoniae Herba ( 仙鶴草 ), Amomi Rotundus Fructus ( 白荳蔲 ), Auriculariae Polyporus ( 黑木耳 ), Carassii Caro ( 鲫鱼 ), Cibotium barometz ( 狗脊 ), Dolichoris Semen ( 白扁豆 ), Drynariae Rhizoma ( 骨碎補 ), Ganodermae Polyporus ( 靈芝 ), Glehniae Radix ( 北沙蔘 ), Cyperi Rhizoma ( 香附子 ), Hepiali Vermis ( 冬虫夏草 ), Cimicifugae Rhizoma ( 升麻 ), Liriopis Tuber ( 麥門冬 ), Longanae Arillus ( 龍眼肉 ), Lonicerae Flos ( 金银花 ), Lycopi Herba ( 澤蘭 ), Massa Medicata Fermentata ( 神曲 ), Mori Fructus ( 桑椹子 ), Morindae 1 Radix ( 巴戟天 ), Nelumbinis Semen ( 蓮子肉 ), Notoginseng Radix ( 参三七 ), Phaseoli Semen ( 赤小豆 ), Phellodendri Cortex ( 黄柏 ), Platycodi Radix ( 桔梗 ), Pogostemi Herba ( 藿香 ), Polygalae Radix ( 远志 ), Polygoni Cuspidati Rhizoma ( 虎杖根 ), Ponciri Fructus Pericarpium ( 枳殼 ), Raphani Semen ( 炒萊菔子 ), Rubiae Radix ( 茜根 ), Schizandrae Fructus ( 五味子 ), Scutellariae Radix ( 黄芩 ), Saposhnikovia Radix ( 防風 ), Trichosanthis Radix ( 天花粉 ), Zedoariae Rhizoma ( 莪朮 ), Zizyphi Spinosae Semen ( 酸枣仁 ) 537

19 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) 2) 정량적분석 (1) 변증의경향성선정된 42개의문헌에서모두변증을제시하였으며, 이중 10개 (23.8%) 의연구에서증상에따른구체적변증과그에따른약물가감의내용을제시하였다. 항암유도백혈구감소증에대해서는 감소증 이라는단어가시사하듯, 한의학에서손상받거나타고난바가부족하여병을물리칠힘이없다는 虛 의개념을 1개를제외한나머지연구에서모두포함하였으며, 그중에서도구체적병증으로정의된 허로 ( 虛勞 ) 를변증으로하는연구는 18편으로많은부분 (43.90%) 을차지하였다. 또한한의학에서증상을분류하는기준중하나인 오장 ( 五臟 ) 의관점을내포한 22개의연구중에서는 비 ( 脾 ) 와 신 ( 腎 ) 이함께작용한다고분류한경우가가장많았다. (2) 처방의경향성 37편의연구에서탕 ( 湯 ) 의형태를사용하였고, 2 편에서산 ( 散 ) 의형태, 2편에서시럽형태, 1편에서는과립 ( 散 ), 1편에서는환 ( 丸 ) 형태의한약을사용하였다. 사용된한약처방중 2회이상사용된한약처방은승백탕류 ( 升白湯類 )( 익기 ( 益氣 )(n=4), 승백탕 (n=3), 쌍황 ( 双黃 ), 황기 ( 黃芪 ), 붕어 ( 鲫鱼 ), 건비익신 ( 健脾益肾 )( 각, n=1)), 건비익 ( 보 ) 신방류 ( 健脾益 ( 補 ) 肾方類 )(n=4), 생백탕류 ( 生白湯類 )( 보기 ( 補氣 ), 보혈 ( 補血 ), 양혈 ( 養血 )( 각, n=1)), 감맥대조탕 ( 甘麦大枣汤 )(n=2), 승혈탕 / 환 ( 升血湯 / 丸 )(n=2) 의순으로나타나, 감소된백혈구를증가시킨다는의미의승백탕류 (n=11) 의처방과, 오장의변증중가장많은빈도를차지했던 비 ( 脾 ) 와 신 ( 腎 ) 의허증을보충하는의미의건비익신방류 (n=4) 가다빈도로사용됨을알수있다. (3) 약물 ( 한약재 ) 의경향성 90가지의한약재가사용되었으며, 25회이상등장하는한약재는황기 ( 黃芪 ), 백출 ( 白朮 ), 당귀 ( 當歸 ) 의 3가지약재였고, 21회이상등장하는한약재는당삼 ( 黨蔘 ), 감초 ( 甘草 ), 여정자 ( 女貞子 ), 계혈 등 ( 鷄血藤 ) 이며, 15회이상등장하는약재는구기자 ( 拘杞子 ), 복령 ( 茯苓 ) 순이었다. 이외다용되는약재는그림에제시된바와같다 (Fig. 3). Fig. 3. Distribution of THM formulas on included RCTs (frequency>10). 3) 메타분석선정된 42개연구중유효율혹은백혈구수변화를결과변수로가지지않은 1편 54 을제외하고중재에따라하위그룹으로분류하여시행한메타분석의결과는 Table 11에제시되어있다. (1) 유효율 (Effective rate) 유효성을평가하기위한양적합성에포함된연구는총 36편이포함되었으며, 중재의유형에따라하위그룹으로나뉘어졌다. Quo 55 의연구는 3-arm study로 THM vs G-CSF 와 THM + G-CSF vs G-CSF 의하위그룹의항목에따라결과값을나누어분석하였으며. Zeng 48 의연구는더욱효과적인한약제제를찾기위해 THM( 산제 ) vs THM( 탕약 ) vs supportive treatment로구성한 3-arm study로이중효과크기가큰 powder 제형의한약과지지요법을비교한연구로간주하여해당하위그룹에포함시켜비교분석하였다. 1 THM vs supportive treatment(n=28)(fig. 4) 총 28편의 RCT 연구가포함되었으며, 한약치료군은지지요법이이루어진대조군에비해백혈구 538

20 김민서 정유진 홍상훈 감소증치료의유효율에유의미한효과를보였다 (N=2673, OR: 5.05, 95% CI; 3.60 to 7.08, p<0.0001, heterogeneity : χ 2 =57.9, p= I 2 =53%). 대조군인지지요법은 leucogen, batilol, Vt B4, creatinine, rubidate 등의단독혹은복합제제를포함하는데, 대조군별하위그룹으로다시나누어효과크기를산출하였을때, leucogen 과 batilol 복합제제를사용한대조군에서는 I 2 =58% 로이질성이높았으나, 나머지하위그룹에서는모두 I 2 <10% 로이질성이상당히감소하는결과를얻을수있었다. i. supportive treatment; leucogen(n=8) 8편 16,17,19,27,31,41,43,46 의연구가포함되었으며, 한약을복용한치료군이지지요법중 leucogen(2-(α-phenyl-αethoxycarbonyl-methyl) thiazolidine-4-carboxylic acid) 을복용한대조군에비해치료유효율에서통계학적으로유의미한결과를보였다 (N=877, OR: 4.07, 95% CI; 2.78 to 5.97, p< , I 2 =6%). ii. supportive treatment; leucogen+batilol(n=7) 7편의연구 20,21,33,36,38,39,45 가포함되었으며, Hao 21 의연구를제외한나머지연구에서한약을복용한치료군이 leucogen 과 batilol(3-octadecyl alkoxyl-1, 2-propylene glycol) 을병용투여한대조군에비해치료유효율이높았으며, 통계학적으로유의미하였으나연구간의이질성은높았다 (N=626, OR: 3.40, 95% CI; 1.60 to 7.24, p=0.001, I 2 =58%). iii. supportive treatment; batilol(n=3) 3편의연구 25,31,34 가포함되었으며, 한약을복용한 치료군이 batilol 을투여한대조군에비해치료유효율은통계학적으로유의미하게현저히높았으며, 세연구간의이질성은없었다 (N=248, OR: 19.87, 95% CI; 7.98 to 49.47, p<0.0001, I 2 =0%). iv. supportive treatment; leucogen+batilol+vt B4(n=2) 2편 30,40 의연구가포함되었으며, 한약을복용한치료군이 leucogen, batilol, Vt B4(6-aminopurine phosphate) 를병용투여한대조군에비해치료유효율이통계학적으로유의성있게높았다 (N=258, OR: 26.35, 95% CI; to 63.29, p< , I 2 =7%). v. supportive treatment; leucogen+vt B4(n=1) 1편의연구 44 에서지유승백탕 ( 鲫鱼升白汤 ) 을처방하고지지요법으로 leucogen 과 Vt B4를함께복용한군과비교한연구결과한약으로치료한집단의유효율이통계적으로유의성있게높았다 (N=54, OR: 20.80, 95% CI; 2.46 to , p=0.008). 2 THM + supportive treatment vs supportive treatment(n=4)(fig. 5) 4편의연구중에서 2편 47,50 이공통으로한약과 batilol 을복합투여하였고, 하나의연구 48 에서한약과 leucogen, batilol, rubidate를, 하나의연구 49 에서 leucogen, batilol, Vt B4를한약과병용투여하고, 각각동일한지지요법을적용한대조군과비교한연구에서치료군의치료유효율이통계학적으로유의미하게높으며, 연구간이질성은없었다 (N=277, OR: 5.39, 95% CI; 2.75 to 10.58, p< , I 2 =0%). 539

21 항암화학요법유발백혈구감소증에대한한약치료의효과 : 체계적고찰및메타분석 ( ) Fig. 4. Forest plot : THM vs supportive treatment, outcome : effective rate [confidence rate]. 540