ÇÐ¼úº¸°í3±Ç¼öÁö

Size: px

Start display at page:

Download "ÇÐ¼úº¸°í3±Ç¼öÁö"

동석 태
5 years ago
Views:

1 병원약사회지 (2018), 제 35 권제 4 호 J. Kor. Soc. Health-syst. Pharm., Vol. 35, No. 4, 409 ~ 417 (2018) Original Article Doxorubicin과 Cyclophosphamide를투여받는유방암환자에서 Pegfilgrastim과 Pegteograstim의비용 -효용분석 권수지 a, 금민정 a, 김재송 a, 손은선 a, 권경희 b, 연세대학교의료원세브란스병원약무국 a, 동국대학교약학대학 b Cost-Utility Analysis of Pegfilgrastim and Pegteograstim in Patients with Breast Cancer using Doxorubicin and Cyclophosphamide Su Ji Kwon a, Min Jung Geum a, Jae Song Kim a, Eun Sun Son a and Kyeng Hee Kwon b, Department of Pharmacy, Severance Hospital, Yon-sei University Health System, 50-1, Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea a College of Pharmacy, Dongguk University, Dongguk University Biomedi Campus 32, Dongguk-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 10326, Republic of Korea b Background : Febrile neutropenia (FN) is one of the side effects in the patients treated with chemotherapy, and the patients who have FN generally need immediate treatment with extended-spectrum antibiotics and hospitalization. Pegfilgrastim and pegteograstim, which are used for the prevention of FN as a granulocyte-colony stimulating factor (G-CSF), have been granted insurance coverage in the Republic of Korea for certain breast cancer patients using doxorubicin and cyclophosphamide (AC) from September Methods : The data of the patients with breast cancer using AC regimen and G-CSF were collected retrospectively. This study involves cost-utility analysis of pegfilgrastim and pegteograstim. In this study, we constructed a simple decision tree model for short-term observation and calculated qualityadjusted life year (QALY) and the direct medical costs from the medical provider s perspective. Results : From September 2016 to May 2017, 15 patients were treated with pegfilgrastim and 15 투고일자 ; 심사완료일자 ; 게재확정일자 교신저자권경희 Tel: Fax: khkwon@dongguk.edu

2 JKSHP, VOL.35, NO.4 (2018) patients were treated with pegteograstim. As a result of dividing the average cost by QALY for each treatment group, it was observed that pegfilgrastim and pegteograstim were consumed 24,923,384 won and 22,808,336 won per 1QALY, respectively. Consequently, incremental cost effectiveness ratio (ICER) showed 2,115,048 won more per pegfilgrastim than pegteograstim per 1QALY, and the cost per 1QALY of both the drugs was lower than 30,500,000 won; the Koreans were willing to pay this amount. Conclusions : This study suggests that pegfilgrastim and pegteograstim can be used to improve the quality of life of breast cancer patients undergoing AC therapy. Among the two drugs, pegteograstim seems to be more cost-effective. However, since this study was conducted as a retrospective observation method on a small scale, it is associated with many limitations. Therefore, a long-term prospective cohort study is needed to supplement the present findings. [Key words] Febrile neutropenia, Breast cancer, Pegfilgrastim, Pegteograstim, Cost-utility analysis 발열성호중구감소증 (febrile neutropenia, 이하 FN) 이란항암화학요법치료를받는환자들에게서주로나타나는부작용중하나로, 발생시보통광범위한항생제치료를위해즉각적인입원이요구되는응급상황이발생할수도있다. 1) 미국국립암연구소 (National Cancer Institute, 이하 NCI) 에서발표한호중구감소증의기준은다음과같으며 (Table 1), FN은 Grade 4 이상의호중구감소증과함께 38.3 이상의열이있는경우, 또는 38 이상의열이 1시간이상지속되는경우를말한다. 2) 이러한 FN을예방하거나치료하기위한약물이 granulocyte-colony stimulating factor( 이하 G-CSF) 제제이다. 이중에서 filgrastim과같은 1 세대 G-CSF는항암화학요법치료중매일투여해야하는불편함이있었다. 따라서이를개선하기위해서 반감기를증가시켜투여빈도를줄인 2세대 G-CSF 제제들이개발되었다. 3) Pegfilgrastim은 filgrastim에 20-kd polyethylene glycol (PEG) 분자를공유결합시켜생산한제제이고, 4) pegteograstim은 filgrastim 에 methoxy-maleimide-peg를결합시킨제제로, 두약제모두 G-CSF 수용체와더높은친화성을가지며긴반감기를얻게된약물이다. 5) 두약제모두6 mg 을항암화학요법을완료하고약 24 시간후피하주사하며, 2018년 2월현재보험상한가는 pegfilgrastim이 782,879원, pegteograstim이 586,656원으로 pegfilgrastim이더고가의약제이다. 환자에게적용되는항암화학요법의종류에따라발열성호중구감소증의발생률은다양하며, 유방암환자의경우다수의환자들이투여받는 doxorubicin과 Table 1 The grade of neutropenia Neutropenia Grade Grade 1 Grade 2 Grade 3 Grade 4 Absolute Neutrophil Count (ANC) Lower limit of normal~1,500/ mm 3 1,000/ mm 3 ~1,500/ mm 3 500/ mm 3 ~1,000/ mm 3 500/ mm 3 *National Cancer Institute : Common Terminology Criteria for Adverse Events (CTCAE) Version

3 권수지 : Doxorubicin 과 Cyclophosphamide 를투여받는유방암환자에서 Pegfilgrastim 과 Pegteograstim 의비용 - 효용분석 cyclophosphamide를이용하는항암화학요법, 즉이하 AC 요법의경우 10~20% 정도의 FN 발생률을나타낸다. 6) 이와같은이유로 2016년건강보험심사평가원에서는 FN을예방하는데사용되는 pegfilgrastim 과 pegteograstim의보험급여기준을변경, 확대하여 AC 요법을투여받는유방암환자들이 65세이상이거나, G-CSF로예방적투여를하지않았던이전주기에서 FN 발생또는호중구수치가 500/mm 3 미만인경우에대해보험급여를인정하였다. 7) 따라서 FN의예방효과가뛰어나고투여편의성역시향상된두약제의사용량도증가하게되었다. 이에본연구의목적은두약제를 Quality-adjusted Life Year ( 이하 QALY) 와함께의료제공자관점에서의직접적의료비용을산출후 AC 요법을투여받는유방암환자에서두약제간비용-효용분석을진행하여 FN의예방적 G-CSF 제제를선택하는데기여하고자한다. 연구설계및방법 거나투여를하였다가중단한환자 - 항암제에관하여임상시험을진행중인환자 - 의무기록누락으로추적이불가능한환자 2. 자료수집본연구의자료수집은전자의무기록을후향적으로검토하여이루어졌으며기관윤리위원회 (Institutional review board, 이하 IRB) 로부터승인후진행하였다 ( 과제번호 : ). 1) 환자특성연구대상환자의특성파악을위하여환자의연령, 성별, 키, 체중, 체표면적, 주진단명, stage, Estern Cooperative Oncology Group ( 이하 ECOG) performance status, 항암화학요법종류, 항암치료전기저 Absolute Neutrophil Count ( 이하 ANC), 예방적투여전 FN 발생여부를수집하였다. 1. 연구대상환자 2) 비용 본연구에서는 2016년 9월 1일부터 2017년 5월 31 일까지의한단일상급종합병원에서외래를통하여항암화학요법치료를시행한유방암환자들중아래기준에따라연구대상자를선정하였다. 1) 선정기준 - 관찰기간내 AC 요법 4주기를모두시행하고종료한환자 - AC 요법 1주기이후매주기마다빠지지않고 pegfilgrastim 또는 pegteograstim을예방적으로투여한환자 2) 제외기준 - 관찰기간내항암치료를종료하지않고중단하거나, 모든항암화학요법치료를관찰할수없는환자 - AC 3주기또는 4주기부터예방적투여를시작하였 본연구에서는연구대상환자의 FN 예방및치료, 항암치료와관련된총입원, 외래비용을수집하고분석하였다. 비용산출의경우관찰기간내외래, 입원시소요된직접의료비를산출하였다. 의약품경제성평가지침에서는, 수년에걸친비용산출에관하여매년 5% 의할인율을적용하도록하고있으나, 8) 본연구에서는연구기간이 1년이내로짧아할인율대신에보건품목의소비자물가상승률 1% 를반영하여계산하였다. 9) 3) 효과해당약제의 FN 예방효과평가를위하여항암제투여후각주기마다의 ANC, AC 요법시작일과종료일, 총항암치료기간, 항암치료중 G-CSF, 항암제, 항생제등을포함한투약내역, 예방적투여후 FN 발생여부를수집하였다. FN 발생의경우의무기록내에 발열성호중구감소증, Febrile Neutropenia,

4 JKSHP, VOL.35, NO.4 (2018) FN 등으로명확히표기되어있는경우, 또는표기가없어도기록상 NCI가정의한조건에맞는경우 FN이발생했다고보았다. 4) 효용및 QALY 본연구에서는선행연구들에서의효용치를참고하여치료일수에해당내용이적용된기간을곱하여 QALY를계산하였다 (Table 2). 10)-12) 효용치 (utility) 는 0을죽음의상태, 1을가장이상적인건강의상태로정의하였다. 환자당평균치료일수와환자상태에해당하는효용치값을해당기간에곱하여계산한 QALY를비교하고자하였다. 이에기대값계산을통해구한각투여군간의관찰기간내평균비용을평균 QALY로나누어 1QALY 당소요비용을비교하고자하였으며, 이를이용하여점증적비용효과비 (incremental cost-effectiveness ratio, 이하 ICER) 를계산하고최종적으로약제간 ICER 값을확인하고자하였다. 13) 본연구에서는, 단기간의관찰에용이한결정수형모델을구축해보았으며기대값계산에필요한값으로는후향적연구결과에따른확률치를이용하였다 (Fig. 1). 3. 통계분석방법 연구결과 Microsoft Office Excel 2016 (Microsoft Corporation, Redmond, WA, USA) 과 IBM SPSS Statistics ver (IBM Co., Armonk, NY, USA) 를이용하여분석하고, p값이 0.05 이하일때통계적으로유의한것으로판정하였다. 연속형자료의경우각항목의정규성을검정하여정규성검정을시행한뒤정규분포가아닐경우는 Mann-Whitney test, 정규성을만족할경우에는독립표본 T 검정을시행하였으며, 범주형자료의경우기대빈도가 5 미만인셀이전체의 20% 를넘지않는경우카이제곱검정을, 기대빈도가 5 미만인셀이 20% 를넘는경우에는 Fisher의정확한검정을시행하였다. 4. 경제성분석모형본연구는후향적연구로치료시작과끝을 AC 요법의시작일과종료일로보았으며, 연구결과를통해각 1. 대상환자분석 2016년 9월 1일부터 2017년 5월 31일까지외래를통하여항암화학요법치료를받은유방암환자는총 966명이었다. 이중관찰기간내 AC 4주기를모두시행한환자중 pegfilgrastim, pegteograstim으로 2주기부터예방적으로 G-CSF를계속해서투여한환자는총 32명이었으며, 제외기준이었던번갈아가며투여한환자 2명을제외한결과, 최종적으로 pegfilgrastim 투여군 15명, pegteograstim 투여군 15명을얻을수있었다. 두군간의기저특성을비교한결과는 Table 3과같으며, 두군간유의한차이는없었다. 2. 연구결과 1) 비용 Table 2 The utility values of each parameter Parameter Value Chemotherapy/G-CSF* 0.70 Chemotherapy Delay 0.50 Hospitalization due to FN 0.33 *G-CSF : Granulocyte-Colony Stimulating Factor FN : Febrile Neutropenia 관찰기간내수집한비용을산출한결과, pegfilgrastim 투여군에서는 3,080,530원이소요되었으며 pegteograstim 투여군에서는 2,787,178원이소요되었다. 2) 효과관찰기간내대상환자를관찰한결과예방적투여

5 권수지 : Doxorubicin 과 Cyclophosphamide 를투여받는유방암환자에서 Pegfilgrastim 과 Pegteograstim 의비용 - 효용분석 Fig. 1 Decision tree-model of cost-utility analysis of pegfilgrastim and pegteograstim Table 3 Patient s characteristics Characteristic Pegfilgrastim (N=15) Pegteograstim (N=15) p-value Age (mean±sd*) 49±9.6 49± Sex, N (%) Female 15(100) 15(100) Male 0(0) 0(0) 1.00 Height, cm (mean±sd) 158.9± ± Weight, kg (mean±sd) 46.2± ± Body Surface Area, m 2 (mean±sd) 1.6± ± Stage, N (%) IA 3(20) 2(13.3) IIA 7(46.7) 3(20) IIB 4(26.7) 5(33.3) 0.33 IIIA 1(6.7) 2(13.3) IIIC 0(0) 3(20) ECOG performance status 15(100) 15(100) 1.00 ANC, count 10 3 /μl (mean±sd) 3.63± ± FN Events before Prophylaxis, N (%) 9(60) 12(80) 0.43 *SD : Standard Deviation, ECOG : Estern Cooperative Oncology Group, ANC : Absolute Neutrophil Count, FN : Febrile Neutropenia

6 JKSHP, VOL.35, NO.4 (2018) 후에도 FN이발생한환자는 pegfilgrastim 투여군에서는한명도없었으며, pegteograstim 투여군에서는 1명이었다. 그러나항암치료기간이연장된환자는 pegfilgrastim에서 2명존재하였으며, pegteograstim의경우는항암치료기간이연장된환자는없었다. 따라서평균치료일수는 pegfilgrastim 투여군은 64.5±1.5일이었으며, pegteograstim 투여군은 63.8±0.4일로 pegfilgrastim의치료일수가더긴것으로나타났다 (p=0.07). 3) 효용및 QALY 선행연구에서의효용치를적용하여 QALY를계산한결과, pegfilgrastim 투여군은 , pegteograstim 투여군은 로 pegfilgrastim을투여할때 QALY가더높은것으로나타났다 (p=0.04). 4) 비용-효용비투여군별로평균비용을 QALY로나눈결과, 1QALY 당 pegfilgrastim은 24,923,384원, pegteograstim 은 22,808,336원이소모되는것으로나타났다. 따라서이둘의차이를계산한결과 ICER는 pegfilgrastim이 pegteograstim에비해 1QALY 당 2,115,048원더소요되는것으로나타났다 (Table 4). 5) 민감도분석본모형의민감도를평가하기위해서기본분석을토대로모형의주요변수에대해민감도분석을수행하였다. 그결과모든경우에서 pegteograstim이우월한대안인것으로나타났다 (Table 5). Table 4 Result of cost-utility analysis Alternatives Cost QALY* Incremental QALY Pegfilgrastim 3,080,530 won Pegteograstim 2,787,178 won Dominated (-2,115,048) *QALY : Quality-Adjusted Life Year Table 5 Sensitivity analysis Parameter Base case Parameter range Incremental QALY* Consumer Price Inflation 1.0% Chemotherapy/G-CSF utility 0.70 Utility of Delaying Chemotherapy 0.50 Utility of Hospitalization due to FN % Dominated (-2,117,327) 2.6% Dominated (-2,256,983) 0.50 Dominated (-2,967,359) 1.00 Dominated (-1,544,973) 0.00 Dominated (-2,318,000) 1.00 Dominated (-2,022,699) 0.24 Dominated (-2,163,346) 0.42 Dominated (-2,175,603) *SD : Standard Deviation, ECOG : Estern Cooperative Oncology Group, FN : Febrile Neutropenia

7 권수지 : Doxorubicin 과 Cyclophosphamide 를투여받는유방암환자에서 Pegfilgrastim 과 Pegteograstim 의비용 - 효용분석 고찰본연구는국내한단일상급종합병원에서 AC 요법을시행하는유방암환자의 pegfilgrastim과 pegteograstim사용에대한비용-효용적가치를평가한연구이다. 연구결과를볼때, 해당환자에서 pegfilgrastim이 pegteograstim에비해같은 QALY 당지불하는비용이많아, pegteograstim이더비용-효용적인것으로사료된다. 그러나한국보건의료연구원에서제시한한국인의평균지불의사금액은 1QALY 당 30,500,000원으로, 14) 두약제모두 1QALY 당소요비용이지불의사금액보다낮으므로, 두약제모두 AC 요법을시행하는유방암환자의삶의질을올리는데도입해볼수있다고사료된다. 본래의약품경제성평가에서는단기간의임상시험종료시점에서최종결과를확인할수없기에전향적인코호트연구를통한확률치를이용한모형구축을통하여중간산출결과를통해최종적인결과를연결하여모형을구축하는것이필요하다. 예를들어 2017년의한연구에서는다른재조합 G-CSF 제제인 lipegfilgrastim과 pegfilgrastim의 FN 예방효과에대한비용-효용분석을시행하였는데, 마르코프모델을통하여 1,000명의유방암환자들을전향적으로코호트추 적하였으며, 그결과 lipegfilgrastim이더비용-효과적임을증명하였다. 15) 그러나본연구는단일기관에서소규모로후향적관찰방법으로진행되어대상환자수가적었으며, 선행연구나임상시험자료의부족으로인해 AC 요법에서의 pegteograstim 사용에대한 FN 발생률과같은확률치를후향적연구결과를통해설정할수밖에없었다. 또한본연구에서는 AC 요법치료종료시점을최종적결과로한결정수형모델을사용하였고, 항암치료이후의최종결과까지의 QALY를구할수없었다는한계점이있다. 추후항암치료종료이후최종적인결과인사망까지모형을구축한추가적연구가필요하며, 이때 Fig. 2와같이항암화학요법기간과나머지생애여명에대하여구축한마르코프모형으로진행할수있다고사료된다. 마르코프모델은환자들이특정시점에발생할수있는모든일련의상황들을나타내어상태간시간의흐름에따른확률변화를이용해장기적이고만성적인질환에있어유용하게쓸수있다는장점이있다. 16) 추가적으로 AC 요법은항암치료종료후항암제로인한심독성이나이차적인암발생, 또는인지저하나신경독성과같은부작용이발생할수있으므로, 이에따라모델구축을할때상태를좀더세분화하여삶의질을평가할수도있을것이다. 17) Fig. 2 Markov model for cost-utility analysis of pegteograstim and pegfilgrastim

8 JKSHP, VOL.35, NO.4 (2018) 비용산출에있어서도각환자를일대일대면인터뷰방식이아니라병원내전산자료를수집하여, 입원료, 진찰료등의대분류를통하여비용을산출하였으며, 환자의교통비나식비등비의료비와유병으로인한생산성손실등의간접비용은포함되지못했다는한계가있다. 따라서추후이를보완한장기간의전향적코호트연구가필요하다고사료된다. 효용치와이를사용하는 QALY의경우임상적인지표보다는측정방법이추상적이며불확실한부분이있으나, 18) 항암치료에서는단순한종양제거나생존기간연장뿐만아니라삶의질을향상시키는부분도역시중요하다. 기존의연구결과에따르면, G-CSF 제제로예방적투여를한환자들을메타분석한결과 FN으로인한조기사망률이 3.4% 로 19) 최종효과평가지표인생존기간의차이는크게없을것으로사료된다. 그러나 FN 예방을위한 G-CSF 제제간효과비교에있어서는생존기간의평가보다는삶의질평가가더중요한부분일것으로사료된다. 이에본연구에서는위에서언급한한계점들에도불구하고, 삶의질을평가할수있는 QALY와그에수반되는비용을이용하여두약제를비교하고분석하였으며, 그로인해아직명확한약제의선정기준이없는 FN적예방목적의 G-CSF 제제선택에도움이된다는점에서의의가있다. 또한, 항암화학요법으로인한 FN 발생예방에많이사용되는 pegfilgrastim과 pegteograstim에대하여, 유방암에대한기존의연구들은 DA (doxorubicin+ docetaxel) 또는 TAC (docetaxel+doxorubicin+ cyclophosphamide) 요법을시행한환자를대상으로한연구가주를이루었으나, 20) 본연구는실제유방암환자에게가장많이사용되는 AC 요법에서의 pegfilgrastim 및 pegteograstim에대한비용-효용분석을시행했다는점에서도의미가있다. 결론본연구결과, AC 요법을시행하는유방암환자에서 FN의예방적목적의 G-CSF 제제에대한비용-효용분석결과 pegteograstim 투여군은 pegfilgastim 투여군과비교하여 1QALY 당 2,115,048원더적게소요 되는것으로분석되었다. 따라서두약제중에서는 pegteograstim이더비용-효용적인대안이될수있다. 단일기관의단기적인후향적연구로진행된본연구의한계점을보완하여추후장기간의전향적코호트연구를진행한다면, 더욱구체화된결과를얻을수있을것으로사료된다. 참고문헌 1) Kuderer NM, Dale DC, Crawford J et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106(10): ) National Institutes of Health NCI. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: U.S.Department of Health and Human Services; 2009 [updated 2010 June May 28]. Available from: 3) Smith TJ, Khatcheressian J, Lyman GH et al Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline. Journal of Clinical Oncology. 2006;24(19): ) Holmes FA, O Shaughnessy JA, Vukelja S et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk Stage II or Stage III/IV breast cancer. Journal of Clinical Oncology. 2002; 20(3): ) Hong J, Lee B, Kang K et al. Characterisation of the site-specific monopegylated rhg-csf analogue pegteograstim. Biologicals. j.biologicals ) Bennett CL, Djulbegovic B, Norris LB et al. Colony-stimulating factors for febrile neu

9 권수지 : Doxorubicin 과 Cyclophosphamide 를투여받는유방암환자에서 Pegfilgrastim 과 Pegteograstim 의비용 - 효용분석 tropenia during cancer therapy. New England Journal of Medicine. 2013;368(12): ) 암환자에게처방 투여하는약제에대한공고개정안내 : Health Insurance Review & Assessment Service; 2016 [updated 2016 Aug 30]. Available from: 8) 의약품경제성평가지침 및작료작성요령 : Health Insurance Review & Assessment Service; 2011 [updated 2012 Feb December]. Available from: 9) e-나라지표소비자물가지수 [Internet] [cited /EachDtlPageDetail.do?idx_cd=1060]. 10) Ramsey SD, Liu Z, Boer R et al. Cost-effectiveness of primary versus secondary prophylaxis with pegfilgrastim in women with early-stage breast cancer receiving chemotherapy. Value in Health. 2009; 12(2): ) Whyte S, Cooper KL, Stevenson MD et al. Cost-effectiveness of granulocyte colony stimulating factor prophylaxis for febrile neutropenia in breast cancer in the united kingdom. Value in Health. 2011;14(4): ) Chan KK, Siu E, Krahn MD et al. Costutility analysis of primary prophylaxis versus secondary prophylaxis with granulocyte colony-stimulating factor in elderly patients with diffuse aggressive lymphoma receiving curative-intent chemotherapy. Journal of Clinical Oncology. 2012;30(10): ) 김철민. Pharmacoeconomics. The journal of Korean society for Clinical Pharmacology and Therapeutics. 2008;16(1): ) 안정훈, 김윤희, 신상진 et al. 보건의료의사결정에서비용 - 효과성에관한아시아공동연구. National Evidence-based Healthcare Collaborating Agency, 2012;12: ) Akpo EIH, Jansen IR, Maes E et al. Costutility analysis of lipegfilgrastim compared to pegfilgrastim for the prophylaxis of chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. Front Pharmacol [Internet]. 2017;8:614. Available from: fphar ) Danova M, Chiroli S, Rosti G et al. Costeffectiveness of pegfilgrastim versus six days of filgrastim for preventing febrile neutropenia in breast cancer patients. Tumori. 2009;95(2): ) Azim JHA, de Azambuja E, Colozza M et al. Long-term toxic effects of adjuvant chemotherapy in breast cancer. Annals of Oncology. 2011;22(9): ) Torrance GW, Feeny D. Utilities and quality-adjusted life years. International Journal of Technology Assessment in Health Care. 2009;5(4): ) Aapro M, Crawford J, Kamioner D. Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now? Supportive Care in Cancer. 2010;18(5) : ) Lee KH, Kim J-Y, Lee MH et al. A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC Supportive Care in Cancer. 2016;24(4):

012임수진

012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar