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1 대한내과학회지 : 제 87 권제 5 호 특집 (Special Review) - 진행성노인암에대한항암요법 진행성노인대장암에대한항암요법 충북대학교의과대학내과학교실 한혜숙 Chemotherapy in Elderly Patients with Colorectal Cancer Hye Sook Han Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Korea Colorectal cancer (CRC) affects largely elderly populations. However, older patients with CRC are generally excluded from randomized clinical trials, and the healthy subjects who are recruited are not representative of the general elderly patient population. Nevertheless, recent data from clinical trials specifically targeting elderly patients and related subgroup analyses indicate that well-selected elderly patients can have a similar response to that of younger patients. Chronological age should not determine the candidacy for adjuvant or palliative chemotherapy in elderly patients with CRC. The appropriate management of healthy elderly patients would mean that they could receive aggressive chemotherapy in a similar regimen to that of younger patients, whereas the care of frail elderly patients and those with a short life expectancy should focus on palliation. The use of a comprehensive geriatric assessment could allow the use of safe and beneficial chemotherapy regimens in elderly patients with CRC. (Korean J Med 2014;87: ) Keywords: Chemotherapy; Colorectal cancer; Elderly 서론의학의발전으로전세계적으로인구의고령화가빠르게진행되고있으며, 우리나라역시통계청의발표자료에따르면 65세이상의인구가차지하는비율이 11% 이며이러한고령화는빠르게진행하여 2018년 14.3%, 2030년 24.3% 로증가할예정이다 [1]. 이에따라노화에의한질병인암의발생및사망도고령인구에서급격히증가하여모든암발생의약 60%, 암사망의약 70% 가 65세이상의인구에서일어나는것으로 알려져있다 [2]. 대장암의경우미국의 SEER (Surveillance, Epidemiology, and End Result) 데이터베이스에의하면대장암의약 70% 가 65세이상, 40% 정도가 75세이상에서발생하고, 우리나라역시 65세이상남자에서대장암은 3번째로높은발생률을보이며여자에서는 1번째로높은발생률을보이고있어우리나라역시노인대장암환자의비율은점차로증가하고있다 [3,4]. 대장암치료의중요한역할을하고있는항암화학요법은근치적수술후재발을줄이는목적으로시행되는보조항 Correspondence to Hye Sook Han, M.D., Ph.D. Department of Internal Medicine, College of Medicine, Chungbuk National University, 52, Naesudong-ro, Seowon-gu, Cheongju , Korea Tel: , Fax: , sook3529@hanmail.net Copyright c 2014 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

2 - Hye Sook Han. Chemotherapy in elderly patients with colorectal cancer - Table 1. Guidelines for evaluating the suitability of chemotherapy in elderly cancer patients Fitness category Criteria Suitability of chemotherapy Group I Fit Totally independent No serious comorbidity Group II Intermediate Dependent in one or more IADLs or with some comorbidity Group III Frail Dependence in one or more ADLs Three or more comorbid conditions One or more geriatric symptoms Full dose treatment, assuming life expectancy is longer than the life expectancy from cancer Consideration of chemotherapy dose reduction for first administration Not suitable for chemotherapy; supportive care recommended ADL, activities of daily living (e.g., transferring, grooming, continence, using the toilet, dressing, feeding); IADL, instrumental activities of daily living (e.g., transportation, money management, shopping, taking medications. preparing meals). 암화학요법 (adjuvant chemotherapy) 과생존기간연장및삶의질향상을목적으로전이성대장암에서시행하는고식적항암화학요법 (palliative chemotherapy) 으로분류할수있다. 최근새로운항암제의도입과분자생물학의발전에따른생물학적표적치료제 (molecular targeted agent) 의개발로대장암의생존기간이유의하게연장되었다. 대장암의항암화학요법의근간이되는약제중의하나인 5-fluorouracil (5-FU) 은 1950년대이후부터현재까지도널리사용되고있고 1980년대이후에는 leucovorin (LV) 이도입되어 5-FU의보조제로서사용되고있으며최근에는 capecitabine 과같은경구용 fluoropyrimidine제제들이소개되어 5-FU의정맥주사에따르는부작용을줄이고치료의편이성을높였다. 2000년대이후에는새로운세대의항암제인 oxaliplatin과 irinotecan의도입으로대장암의치료성적이괄목할만하게향상되었으며, 2000 년대중반이후에는 bevacizumab 또는 cetuximab과같은표적치료제의도입으로전이성대장암의생존율이크게향상되었다. 이렇듯항암화학요법은대장암치료의중요한근간을이루지만그치료독성으로인한부작용을우려하여노인환자의항암화학요법시소극적인치료방침이시행되기쉽다. 또한실제표준항암화학요법을결정하는대부분의선행임상연구들에서 70세이상의환자는 20% 미만이고 75세이상의환자는거의포함되지않을뿐더러, 임상연구에포함된대부분의환자들이전신상태가좋고동반질환이적은환자들이포함되어실제임상현실과많은괴리가있는것이사실이다. 본종설에서는노인대장암환자들에게적용한현재까지의항암화학요법관련연구결과들을살펴보고, 국내현실에서이를어떻게적용할것인지를다루고자한다. 본론노인포괄평가국제노인종양학회 (SIOG; International Society of Geriatric Oncology) 와미국의 NCCN (National Comprehensive Cancer Network) 치료권고안은항암화학요법전 70세이상의노인암환자에게노인포괄평가를시행하여노인암환자를 fit, vulnerable, frail 의세분류로나누고, 건강한 (fit) 노인에게는표준용량의항암화학요법을권유하고노쇠한 (frail) 노인에게는항암화학요법을권유하지않거나독성이적은표적치료제를권유하며중간단계의 (vulnerable) 노인에게는보존적치료와재활치료를통하여건강한상태를만드는것을목표로하되용량을조절한항암화학요법을시도할것을권유하고있다 [5,6]. 노인대장암환자의항암화학요법결정시에는연령이라는절대적인나이 (chronological age) 에따라항암화학요법을결정하는것이아니라환자의상태를정확하게평가할수있는기능상태 (functional status), 동반질병 (comorbidity), 기대여명 (life expectancy) 등을다각적, 포괄적으로평가하여같은나이라도각각다른치료방침을결정할수있다 (Table 1). 수술후보조항암화학요법여러무작위 3상연구에서수술후 2-3기의결장암 (colon cancer) 환자에서수술후보조항암화학요법으로 5-FU/LV (FL) 요법을시행한경우유의한생존율증가가있음이증명되었다. 경구형 fluoropyrimidine제제인 capecitabine 은수술후 3기결장암환자를대상으로 FL 요법과비교한대규모 3 상연구결과, 무질병생존율과전체생존율면에서동등함을보였고 3도이상의부작용은 capecitabine군에서더적음이

3 - 대한내과학회지 : 제 87 권제 5 호통권제 651 호 증명되었다 [7]. 그러나 capecitabine 은신기능에영향을받으므로신기능이저하된노인환자에서는주의하여사용해야한다 [8]. 수술후 2-3기결장암에서단일요법이아닌복합요법의효능을보기위해 FL 요법과 5-FU, LV, oxaliplatin 을병합한 FOLFOX 요법을비교하는대규모 3상연구 (MOSAIC) 가 1998년부터 2001년까지총 2,246명의결장암환자를대상으로시행되었고, FOLFOX 요법을시행한환자군에서무병생존율과전체생존율모두통계적으로우월함이관찰되었다 [9]. 그러나 3기에서는 FOLFOX군의생존율향상이통계적으로우월한데반하여, 2기에서는두군간의차이가유의하게관찰되지않았다. 경구형 fluoropyrimidine제제인 capecitabine과관련한연구결과에서는 3기결장암의수술후보조항암화학요법에서 XELOX 요법은 FOLFOX 요법을대치할수있는또다른요법으로입증되어현재수술후보조요법으로널리사용되고있다 [10]. 이러한수술후항암화학요법의유의한생존율의증가에도불구하고항암화학요법에따른합병증과기대여명에대한우려때문에실제 3기결장암환자 86,000명을대상으로시행한후향적분석에따르면 1990년부터 2002년까지연령별수술후보조항암화학요법을시행한빈도는 70세미만 80%, 70-79세 70%, 80세이상 40% 로분석되었다 [11]. 고령의대장암환자에게보조항암화학요법이실제생존율향상에도움이되는지는현재까지고령의환자만을대상으로한임상연구는없으므로기존의대규모보조항암화학요법관련임상연구대상환자중에서고령환자의자료만을분석한연구들을근간으로가늠해볼수있겠다. 수술후보조항암화학요법에관한 7개의임상연구들에포함된 3,351명의 2-3 기결장암환자들의 pooled analysis 결과를보면 70세이상의노인환자들의 5-FU 근간의항암화학요법으로부터얻는생존율의증가나독성의빈도는 70세미만의환자들과차이가없었다 [12]. 또한 67세이상의 3,357명의 3기결장암환자들을대상으로한코호트연구에서도수술단독군에비해수술후보조항암화학요법군에서유의한생존율의향상을보였다 [13]. 그러므로 70세이상의노인대장암환자에서 5-FU 근간의보조항암화학요법은 70세미만의환자와동등한생존율의득이있다고하겠다. 그러나노인대장암환자에서 FOLFOX 병합요법에대해서는아직이견이많다. MOSAIC 연구에서는 65세이상의고령의환자에서는 FOLFOX 요법이그생존율에있어서는 FL 요법과차이가없었고 [9], 보조 항암화학요법에관한 7개의 3상연구분석결과 ( 전체 14,528 명, 70세이상의노인환자 2,575명 ) 에서도 oxaliplatin을병합하는것이 70세이상의환자에서단기재발률을줄일수는있으나전체생존기간에미치는영향은불확실하였다 [14]. 최근 2004년부터 2007년까지 75세이상의 3기결장암환자 5,489명을대상으로한보조항암화학요법에관한후향적연구에서는 oxaliplatin을포함한요법에서의약간의생존율의증가가관찰되었다 [15]. 하지만위임상연구결과들은노인환자만을대상으로이루어진임상연구들이아니고, 전체대상군에서노인환자만을추출하여분석한연구들이기때문에비교적전신상태가좋고동반질환이적은노인환자들이임상연구에포함되었을선택의오류가있다. 또한노인암환자의약 1/3은보조항암화학요법을완료하지못하므로그효과를반감시킬수있고암이외의동반질환에의한사망도많기때문에암의치료만의효과가전체생존율의증가를반드시반영하지못한다는한계가있으므로그결과의해석에주의가필요하다. 요약하면, 고령의환자에서도수술후보조항암화학요법의효과가전체다른환자와유사한정도로있을수있으므로나이만으로보조항암화학요법의시행여부를결정하는것은적절하지않다. 3기의노인결장암환자에게서는 FL 혹은 capecitabine 의 fluoropyrimidine 단일요법을고려하는것이좋겠으며, 전신상태가비교적좋은건강한 3기결장암노인환자의경우젊은환자와마찬가지로 FOLFOX 혹은 XELOX 같은복합요법또한고려해볼수있겠다. 전이성대장암의고식적항암화학요법 1. 세포독성항암제최근약제의발전에따라전이성대장암의생존율은크게향상되어 5-FU, LV, oxaliplatin, irinotecan 등의표준세포독성항암제의경우약 20개월, bevacizumab, cetuximab 등의표적치료제를적절히병합하여사용한경우약 30개월까지도중앙생존기간이보고되고있다. 전이성대장암에서의고식적항암화학요법의표준은 5-FU를기본으로하는 2제병합요법으로, 5-FU/LV에 oxaliplatin을병합하는 FOLFOX 요법과 5-FU/LV 에 irinotecan을병합하는 FOLFIRI 요법이근간을이루고있다. Capecitabine의경우 FL 요법에비해효과면에

4 - 한혜숙. 진행성노인대장암에대한항암요법 - 서는동등하며부작용면에서는우월함이알려져 FOLFOX 요법혹은 FOLFIRI 요법을 XELOX (capecitabine/oxaliplatin) 혹은 XELIRI (capecitabine/irinotecan) 요법으로대체하고자하는연구가많이시행되어왔다. XELOX 요법의경우 FOLFOX 요법에비해효과와부작용면에서거의동등함을보이나 [16, 17] XELIRI 요법의경우는 FOLFIRI 요법와비교하여효과면에서도약간열등하고부작용도많은것으로알려져 [18], 현재 capecitabine 을사용한고식적항암화학요법은 XELOX 요법만이사용되고있다. 노인환자에서의고식적항암화학요법에관련된연구들을살펴보면, 전이성대장암으로 5-FU를치료받았던 70세이상의 629명의환자를대상으로한 22개의 2상혹은 3상연구들에대한후향적연구결과를보면종양반응률, 무진행생존율, 전체생존율모두 70세미만의환자들에비해큰차이가없음을보였으며 bolus 5-FU 요법에비해 infusional 5-FU 요법이보다효과적임을보였다 [19]. 70세이상의노인전이성대장암환자를대상으로한 capecitabine 의 2상연구결과에서는 24% 의반응률, 7개월의무진행생존기간, 11개월의전체생존기간을보였고수족증후군, 설사등의 3도이상의부작용은 12% 의환자에서나타났다 [20]. 단일요법이아닌현재표준항암화학요법인 FOLFIRI, FOLFOX, XELOX 등의병합요법과관련된노인대장암환자들에서의연구들은다음과같다. Folprecht 등은전이성대장암의 1차요법으로서 FL 요법과 FL/irinotecan 병합요법을비교한 4개의 3상임상연구 (70세미만, 2,092명 ; 70세이상, 599명 ) 를분석한결과, 70세이상에서 irinotecan을병합했을때전체생존율은큰차이가없었으나반응률, 무진행생존율에서 FL 요법에비해유의한증가를보였으며독성에있어서도나이에따라큰차이를보이지않음을보고하였다 [21]. Fluoropyrimidine과 irinotecan의병합요법의효능을본 BICC-C 연구에서 70세이상의노인환자만을대상으로분석했을때, 70세이상과 70세미만에서반응률, 무진행생존율, 전체생존율, 부작용등에서유의한차이를보이지않았다 [22]. Goldberg 등은수술후보조항암화학요법, 1차그리고 2차고식적항암화학요법에서 FOLFOX를시행한 4개의임상연구들을종합하여분석한결과, 70세이상에서반응률, 무진행생존율, 전체생존율, 3도이상의부작용의빈도가 70세미만의환자와다르지않았음을발표하였다 [23]. 그러나노인대장암환자를대상으로한복합항암화학요법에대한상기연구결 과들은역시전신상태가좋고동반질환이적은노인환자들이포함된임상연구들의분석이기때문에실제임상에서전신상태가좋지못하고동반질환이많은노인환자들에게적용하기에는세심한주의가필요하다. MRC FOCUS 2 연구는전이성노인대장암환자에서 oxaliplatin 병합요법의효능을본연구로, 적정용량의복합항암화학요법의적응증이되지않는노인환자를대상으로 infusional FL, capecitabine, FOLFOX, XELOX 4개요법의효능을비교한연구이다 [24]. 본연구에포함된환자들의평균나이는 74세였고, 40% 가 75세이상, 13% 가 80세이상의환자였다. 그결과 oxaliplatin 병합요법이단일요법에비해반응률은유의하게향상시켰으나무진행생존율및전체생존율에서큰차이가없었으며환자의삶의질은 fluoropyrimidine 단일요법이 oxaliplatin 병합요법에비해유의하게향상됨을보였고경구 capecitabine 은 5-FU에비해삶의질을향상시키지는못했다. 요약하면, 전이성대장암을가진고령의환자에서도완치적목적의전이절제술의가능성이있거나종양으로인한증상이있는전신상태가비교적좋은노인환자에게는복합항암화학요법이도움이되리라생각되나, 전신상태가좋지않거나동반질환이많은노인환자에게는복합항암화학요법이 fluoropyrimidine 단일요법에비해생존율의증가나삶의질향상을가져오지는못하므로 fluoropyrimidine 단일요법을권유하는것이좋겠다. 그리고노인환자에게서는적절하게항암휴지기 (chemotherapy-free intervals) 를두어항암화학요법의치료기간을단축하고이로이한독성을줄이며삶의질을개선하려는노력또한중요하게고려해야할점이다. 2. 표적치료제현재국내에서전이성대장암에사용중인대표적인표적치료제는 bevacizumab과 cetuximab이있다. 이러한표적치료제는단독으로는효과가없고세포독성항암제와병합을추천하고있으며, 현재우리나라에서는 1차치료제로 FOLFIRI 와의병합요법만이보험급여가인정되는상황이어서이에대한득실을잘고려하여선택하여야한다. Bevacizumab Bevacizumab은혈관내피세포성장인자 (vascular endothelial growth factor, VEGF) 에대한단클론항체로 bevacizumab 병합요법이항암제단독요법에비해유의하게생존기간이향상됨이여러연구에서발표된이후전이성대장암의 1차혹은

5 - The Korean Journal of Medicine: Vol. 87, No. 5, 차요법에서세포독성항암제와병합하여사용되고있다. Fluoropyrimidine 근간의항암화학요법단독과 bevacizumab 병합요법을비교한 4개의연구를분석한결과, bevacizumab 병합요법은나이에상관없이유의한무진행생존기간의증가를보였고혈전색전증을제외한부작용의빈도도나이에따라큰차이를보이지않았다 [25]. 최근 70세이상의전이성대장암환자 280명을대상으로 capecitabine 단독과 bevacizumab/capecitabine 병합요법을비교한 3상연구결과가발표되었다. 그결과 capecitabine 단독군에비해 bevacizumab/ capecitabine 병합요법군에서유의한무진행생존기간의증가 (5.1개월대 9.1개월, p < ) 를보였으며 bevacizumab과관련된 3도이상의부작용은수족증후군, 혈전색전증이외에큰빈도의차이를보이지않았다 [26]. 그러나 bevacizumab/capecitabine 병합요법은우리나라에서보험급여가인정되지않고, 현재국내에서 1차치료로 bevacizumab과병용하였을때보험급여가인정이되는항암화학요법은 FOLFIRI 요법이므로국내의현실을고려하여 bevacizumab을사용한다면 FOLFIRI 요법과의병합을고려해볼수있겠다. Bevacizumab과관련된부작용은고혈압, 단백뇨, 출혈, 상처부위합병증, 혈전색전증, 장천공등의일반적인혈관생성억제제가가지는부작용을갖는다. 대부분의연구결과혈전색전증을제외하고는나이에따라큰차이가없으나, 최근심뇌혈관계주요사건이있었던경우나조절이되지않는고혈압, 불안정협심증, 부정맥등이있는경우에는 bevacizumab 사용을신중히고려하여야한다. Cetuximab Cetuximab 은상피세포성장인자수용체 (epithelial growth factor receptor, EGFR) 에대한단클론항체이며이는 1차요법뿐아니라, 표준세포독성항암요법에모두실패한경우에도 cetuximab 과 irinotecan 을병합하여추가생존율향상을보였다. 기존의연구결과들이 cetuximab이 EGFR 에대한단클론항체이기때문에환자의선택기준을종양조직에서 EGFR 면역화학염색결과가양성인경우로제한하였으나, 최근연구결과 cetuximab 의효과는 EGFR 의발현정도와상관없이 EGFR 신호전달체계에관여하는유전자중하나인 RAS의돌연변이여부에따라다르다는것이밝혀졌다. RAS에돌연변이가있는경우 EGFR 신호전달체계가영구적으로활성화되어상위단계인 EGFR 을차단하여도세포증식이지속적으로이루어지게되 므로 RAS에돌연변이가없을경우 cetuximab이세포증식을막을수있는예측인자 (predictive marker) 가되어 RAS 야생형 (wild-type) 인경우에한해 cetuximab이종양에대한반응을유도할수있다 [27,28]. 노인대장암환자에서 cetuximab의효능에대해서는그동안많은연구가이루어지지않았다. Cetuximab 과 capecitabine 을병합한 2상연구에서는유의한반응을얻지못하였으며피부발진, 수족증후군, 설사등의빈도도높음을보였다 [29]. 최근 cetuximab과 FOLFIRI 요법 (CRYSTAL) 혹은 FOLFOX 요법 (OPUS) 과의병합요법을항암화학요법단독과비교한두개의 3상연구의분석결과, KRAS 야생형노인대장암환자에서 cetuximab의병합요법에서항암화학요법단독에비해유의한생존율의증가를보임을발표하였다 [30]. 노인대장암환자에서 1차요법으로 cetuximab 근간의항암화학요법은아직그근거가많지않은상태이며, 현재우리나라에서 cetuximab과병용하였을때보험급여가인정이되는항암화학요법역시 FOLFIRI 요법이므로, cetuximab을사용한다면 RAS 돌연변이검사를통해돌연변이가관찰되지않을경우 FOLFIRI 요법과의병합을고려할수있겠으나노인환자에서는독성을고려하여환자선정에세심한주의가필요하겠다. 결론 3기노인결장암의수술후보조항암화학요법에서는 FL 혹은 capecitabine 의 fluoropyrimidine 단독요법을고려하는것이좋겠으며, 전신상태가비교적좋은건강한 3기결장암노인환자의경우 FOLFOX 혹은 XELOX 같은복합요법또한고려해볼수있겠다. 전이성대장암을가진노인환자에게는 fluoropyrimidine 근간의고식적항암화학요법은유의한생존율의증가가있으며전신상태가좋고동반질환이없는건강한노인대장암환자에게는복합항암화학요법을시행할수있고그렇지않은노인대장암환자에게는 infusional 5-FU 혹은 capecitabine의 fluoropyrimidine 단독제제를사용하는것을권유한다. Bevacizumab 혹은 cetuximab과같은표적치료제의사용은치료의목적, 부작용및예측인자, 국내에서병합하여사용가능한항암화학요법의종류등을고려하여환자군선정에세심한주의가필요하겠다 (Table 2)

6 - Hye Sook Han. Chemotherapy in elderly patients with colorectal cancer - Table 2. Recommendation of chemotherapy in elderly patients with colorectal cancer Stage Fit Pre frail or vulnerable Frail Stage III FOLFOX or XELOX or Fluoropyrimidine Observation Fluoropyrimidine a Stage IV Potentially resectable metastases after chemotherapy Tumor related symptoms Multiple metastases and low aggressive disease Doublet chemotherapy (± targeted agent) Doublet chemotherapy (± targeted agent) Bevacizumab + capecitabine b or Fluoropyrimidine Bevacizumab + capecitabine or Fluoropyrimidine Bevacizumab + capecitabine or Fluoropyrimidine or Doublet chemotherapy (± targeted agent) c Bevacizumab + capecitabine or Fluoropyrimidine BSC Bevacizumab + capecitabine or Fluoropyrimidine or BSC FOLFOX, 5 fluorouracil, leucovorin, and oxaliplatin; XELOX, capecitabine and oxaliplatin; BSC, best supportive care. a 5 fluorouracil/leucovorin or capecitabine (For capecitabine, dose reduction according to creatinine clearance is necessary). b The combination of bevacizumab and capecitabine is not covered by insurance in South Korea. c In the first cycle, consider reduce doses and increase it according to the toxicity profile. BSC 고령의환자에서도항암화학요법의효과가전체다른환자와유사한정도로있을수있으므로, 나이만으로항암화학요법의시행여부및요법의종류를결정하는것은적절하지않은것으로생각된다. 하지만노인환자에게는동반되는질환이흔하고암이외의원인으로인한사망도적지않으므로모든환자에게가이드라인에따른항암화학요법을일률적으로투여하는것보다는기능상태 (functional status), 동반질병 (comorbidity), 영양상태 (nutritional status), 인지기능 (cognitive function), 정신건강 (psychological state), 사회환경 (social support), 기대여명 (life expectancy) 등여러구체적인지표들을통해환자를포괄적으로평가하여항암화학요법을결정하는것이필요하겠다. 중심단어 : 항암화학요법 ; 대장암 ; 노인 REFERENCES 1. Statistic Korea [Internet]. Daejeon: Statistics Korea; 2014 [cited 2014 Jan 24]. Available from: 2. Yancik R. Population aging and cancer: a cross-national concern. Cancer J 2005;11: National Cancer Institute. SEER Cancer Statistics Review (CSR) [Internet]. Bethesda (MD): National Cancer Institute, c2011 [cited 2013 Oct 20]. Available from: 4. Jung KW, Won YJ, Kong HJ, Oh CM, Lee DH, Lee JS. Prediction of cancer incidence and mortality in Korea, Cancer Res Treat 2014;46: Wildiers H, Heeren P, Puts M, et al. International society of geriatric oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014 Jul 28[Epub]. pii: JCO National Comprehensive Cancer Network. NCCN Practice Guidelines in Oncology: Senior Adult Oncology [Internet]. Washington (PA): National Comprehensive Cancer Network, c2014 [cited 2014 Jan 11]. Available from: org/professionals/physician_gls. 7. Twelves C, Wong A, Nowacki MP, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005;352: Cassidy J, Twelves C, Van Cutsem E, et al; Capecitabine Colorectal Cancer Study Group. First-line oral capecitabine therapy in metastatic colorectal cancer: a favorable safety profile compared with intravenous 5-fluorouracil/leucovorin. Ann Oncol 2002;13: André T, Boni C, Mounedji-Boudiaf L, et al; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350: Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011;29:

7 - 대한내과학회지 : 제 87 권제 5 호통권제 651 호 Jessup JM, Stewart A, Greene FL, Minsky BD. Adjuvant chemotherapy for stage III colon cancer: implications of race/ethnicity, age, and differentiation. JAMA 2005;294: Sargent DJ, Goldberg RM, Jacobson SD, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 2001;345: Iwashyna TJ, Lamont EB. fectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. J Clin Oncol 2002;20: McCleary NJ, Meyerhardt JA, Green E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol 2013;31: Sanoff HK, Carpenter WR, Stürmer T, et al. Effect of adjuvant chemotherapy on survival of patients with stage III colon cancer diagnosed after age 75 years. J Clin Oncol 2012;30: Hochster HS, Hart LL, Ramanathan RK, et al. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol 2008;26: Rothenberg ML, Cox JV, Butts C, et al. Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol 2008;19: Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol 2008;26: Folprecht G, Cunningham D, Ross P, et al. Efficacy of 5-fluorouracil-based chemotherapy in elderly patients with metastatic colorectal cancer: a pooled analysis of clinical trials. Ann Oncol 2004;15: Feliu J, Escudero P, Llosa F, et al. Capecitabine as first-line treatment for patients older than 70 years with metastatic colorectal cancer: an oncopaz cooperative group study. J Clin Oncol 2005;23: Folprecht G, Seymour MT, Saltz L, et al. Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials. J Clin Oncol 2008;26: Jackson NA, Barrueco J, Soufi-Mahjoubi R, et al. Comparing safety and efficacy of first-line irinotecan/fluoropyrimidine combinations in elderly versus nonelderly patients with metastatic colorectal cancer: findings from the bolus, infusional, or capecitabine with camptostar-celecoxib study. Cancer 2009;115: Goldberg RM, Tabah-Fisch I, Bleiberg H, et al. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 2006;24: Seymour MT, Thompson LC, Wasan HS, et al; FOCUS2 Investigators; National Cancer Research Institute Colorectal Cancer Clinical Studies Group. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet 2011;377: Cassidy J, Saltz LB, Giantonio BJ, Kabbinavar FF, Hurwitz HI, Rohr UP. Effect of bevacizumab in older patients with metastatic colorectal cancer: pooled analysis of four randomized studies. J Cancer Res Clin Oncol 2010;136: Cunningham D, Lang I, Marcuello E, et al; AVEX study investigators. Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 2013;14: Douillard JY, Oliner KS, Siena S, et al. Panitumumab- FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013;369: Sorich MJ, Wiese MD, Rowland A, Kichenadasse G, McKinnon RA, Karapetis CS. Expended RAS mutations and anti-egfr monoclonal antibody survival benefit in metastatic colorectal cancer: a meta-analysis of randomized controlled trials. Ann Oncol 2014 Aug 12[Epub]. pii: mdu Sastre J, Grávalos C, Rivera F, et al. First-line cetuximab plus capecitabine in elderly patients with advanced colorectal cancer: clinical outcome and subgroup analysis according to KRAS status from a Spanish TTD Group Study. Oncologist 2012;17: Folprecht G, Kohne C, Bokemeyer C, et al. Cetuximab and 1st line chemotherapy in elderly and younger patients with metastatic colorectal cancer (mcrc): a pooled analysis of the CRYSTAL and OPUS studies. Ann Oncol 2010;21 (Suppl. 8): abstract 597P

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untitled 대한소화기학회지 2009;54:355-363 DOI: 10.4166/kjg.2009.54.6.355 REVIEW 대장암의항암화학요법 울산대학교의과대학서울아산병원종양내과학교실 홍용상ㆍ김태원 Chemotherapy for Colorectal Cancer Yong Sang Hong, M.D. and Tae Won Kim, M.D. Department of Oncology,