<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medsovet</journal-id><journal-title-group><journal-title xml:lang="ru">Медицинский Совет</journal-title><trans-title-group xml:lang="en"><trans-title>Meditsinskiy sovet = Medical Council</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2079-701X</issn><issn pub-type="epub">2658-5790</issn><publisher><publisher-name>REMEDIUM GROUP Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21518/2079-701X-2018-19-42-49</article-id><article-id custom-type="elpub" pub-id-type="custom">medsovet-2745</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Химиотерапия злокачественных опухолей</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Malignant tumor chemotherapy</subject></subj-group></article-categories><title-group><article-title>Результаты использования тегафура в комбинации с иринотеканом и оксалиплатином у пациентов с распространенным колоректальным раком</article-title><trans-title-group xml:lang="en"><trans-title>Results of using tegafur in combination with irinotecan and oxaliplatin in patients with advanced colorectal cancer</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Доброва</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Dobrova</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., старший научный сотрудник отделения химиотерапии и комбинированного лечения злокачественных опухолей НИИ клинической онкологии</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Борисова</surname><given-names>Е. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Borisova</surname><given-names>E. I.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., старший научный сотрудник отделения химиотерапии и комбинированного лечения злокачественных опухолей НИИ клинической онкологии</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Даренская</surname><given-names>А. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Darenskaya</surname><given-names>A. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>к.м.н., младший научный сотрудник отделения химиотерапии и комбинированного лечения злокачественных опухолей НИИ клинической онкологии</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Блохина» Минздрава России, Москва</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Blokhin National Medical Research Cancer Centre, Federal State Budgetary Institution of the Ministry of Health of Russia. Moscow</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>11</day><month>11</month><year>2018</year></pub-date><volume>0</volume><issue>19</issue><fpage>42</fpage><lpage>49</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Доброва Н.В., Борисова Е.И., Даренская А.Д., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Доброва Н.В., Борисова Е.И., Даренская А.Д.</copyright-holder><copyright-holder xml:lang="en">Dobrova N.V., Borisova E.I., Darenskaya A.D.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.med-sovet.pro/jour/article/view/2745">https://www.med-sovet.pro/jour/article/view/2745</self-uri><abstract><p>С целью разработки и изучения трехкомпонентного режима с пероральным фторпиримидином тегафуром (Фторафуром) для амбулаторной практики проведено исследование, в которое были включены 30 пациентов с распространенным колоректальным раком, не получавших ранее специфического лекарственного лечения. Оценены время до прогрессирования болезни (ВБП), общая выживаемость (ОВ) пациентов, получавших иринотекан + оксалиплатин + Фторафур в первой линии, а также эффективность и безопасность этого режима. У 6 пациентов был применен 3-недельный режим (рис. 1), у 24 пациентов – 2-недельный режим (рис. 2) химиотерапии. В настоящее время получены предварительные результаты. Медиана ОВ не достигнута, медиана ВБП составила 8,5 мес. В I группе частичная регрессия метастазов достигнута у 3/6 пациентов, длительная стабилизация болезни (≥ 6 мес.) отмечена еще у 3 больных. Лечебный эффект (частичная ремиссия + длительная стабилизация ≥ 6 мес.) отмечен у всех пациентов. Длительность ВБП была от 6 до 15 мес. Во II группе эффект оценен у 24 пациентов, получивших как минимум 2 курса химиотерапии. У 14/24 больных отмечен частичный ответ (ЧО), из них 4 (16,6%) пациента радикально прооперированы, у 6 пациентов отмечалась стабилизация болезни. Таким образом, контроль над болезнью достигнут у 83,33% больных во II группе. Комбинация оксалиплатина, иринотекана и фторафура была эффективной, имела приемлемый профиль токсичности, в связи с чем может быть использована у ослабленных пациентов с диссеминированной болезнью.</p></abstract><trans-abstract xml:lang="en"><p>A study that enrolled 30 patients with advanced colorectal cancer, who had not previously received any specific drug treatment, was conducted to develop and study a three-component regimen with oral fluoropyrimidine tegafur (Ftorafur) in outpatient practice. The study evaluated the time to disease progression (TDP), the overall survival (OS) of patients, who received irinotecan + oxaliplatin + Ftorafur in the first-line therapy, as well as the effectiveness and safety of this regimen. 6 patients received a 3-week chemotherapy cycle (Fig. 1), 24 patients – a 2-week chemotherapy cycle (Fig. 2). The preliminary results of the study have been obtained. The median OS was not reached, the median TDP was 8.5 months. In Group I, there was partial regression of metastasis in 3/6 patients, and prolonged disease stabilization (≥ 6 months) in 3 patients. The therapeutic effect (partial remission + long-term stabilization ≥ 6 months) was observed in all patients. The duration of TDP was from 6 to 15 months. In group II, the effect was evaluated in 24 patients, who received at least 2 chemotherapy cycles. 14/24 patients had a partial response (PR), of which 4 (16.6%) patients were radically operated, 6 patients elicited disease stabilization. Thus, control over the disease was achieved in 83.33% of patients in Group II. Oxaliplatin combined with irinotecan and fluorafur was effective, had an acceptable toxicity profile, and therefore, can be used in debilitated patients with disseminated disease.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>колоректальный рак</kwd><kwd>химиотерапия</kwd><kwd>иринотекан</kwd><kwd>оксалиплатин</kwd><kwd>фторафур</kwd><kwd>первая линия лекарственной терапии</kwd></kwd-group><kwd-group xml:lang="en"><kwd>colorectal cancer</kwd><kwd>chemotherapy</kwd><kwd>irinotecan</kwd><kwd>oxaliplatin</kwd><kwd>ftorafur</kwd><kwd>first-line therapy</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Каприн А.Д. Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена – филиал ФГБУ «ФМИЦ им. П.А. Герцена» Минздрава России, 2015. 250 с.</mixed-citation><mixed-citation xml:lang="en">Kaprin AD. Malignant neoplasms in Russia in 2013 (morbidity and mortality). Under the editorship of Kaprin AD, Starinsky VV, Petrova GV, M.: Hertsen Moscow Oncology Research Center - branch of FSBI NMRRC of the Ministry of Health of Russia, 2015. 250 p.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Манзюк Л.В., Переводчикова Н.И., Горбунова В.А. и др. Фторафур – первый пероральный фторпиримидин в терапии метастатического колоректального рака. Современная онкология, 2001, 3(4): 32-34.</mixed-citation><mixed-citation xml:lang="en">Manzyuk LV, Perevodchikova NI, Gorbunova VA, et al. Ftorafur is the first oral fluoropyrimidine in the treatment of metastatic colorectal cancer. Sovremennaya Onkologiya, 2001, 3 (4): 32-34.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Семенов Н.Н. Комбинированное лечение метастазов колоректального рака в печень. Русский медицинский журнал, 2002, 24: 1109- 1111</mixed-citation><mixed-citation xml:lang="en">Semenov NN. Combined treatment for colorectal liver metastases. Russkiy Medicinskiy Zhurnal, 2002, 24: 1109-1111.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Тюляндин С.А., Трякин А.А., Федянин М.Ю. Химиотерапия больных распространенным раком толстой кишки. Современная онкология, 2010, 2: 18-24.</mixed-citation><mixed-citation xml:lang="en">Tyulyandin SA, Tryakin AA, Fedyanin MYu. Chemotherapy for patients with advanced colon cancer. Sovremennaya Onkologiya, 2010, 2: 18-24.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Горбунова В.А., Орел Н.Ф., Бесова Н.С. и др. Современные достижения в клинической химиотерапии злокачественных опухолей. Российский биотерапевтический журнал, 2003, 2: 15-26</mixed-citation><mixed-citation xml:lang="en">Gorbunova VA, Oryol NF, Besova NS, et al. Advances in clinical chemotherapy for malignant tumors. Rossiyskiy Bioterapevticheskiy Zhurnal, 2003, 2: 15-26</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Доброва Н.В. Комбинация тегафура (фторафура), лековорина и оксалиплатина (TELVOX) – новый эффективный режим 1 линии химиотерапии при метастазах колоректального рака. РМЖ, 2011, 1: 18-24.</mixed-citation><mixed-citation xml:lang="en">Dobrova NV. The combination of tegafur (ftorafura), lecovorin and oxaliplatin (TELVOX) is a new effective regimen of first-line chemotherapy for colorectal cancer metastases. RMJ, 2011, 1: 18-24.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Личиницер М.Р., Семенов Н.Н. Новые горизонты в применении Оксалиплатина (Элоксатина) Фарматека, 2004, 18: 21-25</mixed-citation><mixed-citation xml:lang="en">Lichinitser MR, Semenov NN. New prospects for using Oxaliplatin (Eloxatin) Pharmateca, 2004, 18: 21-25.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Личиницер М.Р. Оксалиплатин (Элоксатин): новые возможности лечения больных раком и лимфомой. Международный журнал медицинской практики, 2001, 2: 69-72.</mixed-citation><mixed-citation xml:lang="en">Lichinitser MR. Oxaliplatin (Eloxatin): new treatment options for patients with cancer and lymphoma. Mezhdunarodnyy Zhurnal Medicinskoy Praktiki, 2001, 2: 69-72.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Личиницер М.Р. Оксалиплатин (Элоксатин): новые возможности лечения больных раком и лимфомой Провизор, 2001,19: 39-41.</mixed-citation><mixed-citation xml:lang="en">Lichinitser MR. Oxaliplatin (Eloxatin): new treatment options for patients with cancer and lymphoma Provisor, 2001.19: 39-41</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Семенов Н.Н. Активность оксалиплатина (Элоксатина) при платиночувствительных опухолях. Фарматека, 2005, 18: 63-65.</mixed-citation><mixed-citation xml:lang="en">Semenov NN. Oxaliplatin (Eloxatin) activity in platinum-sensitive tumors. Pharmateca, 2005, 18: 63-65.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Жукова Л.Г., Личиницер М.Р., Семенов Н.Н. и др. Исследование эффективности и безопасности схемы иритен (иринотекан)+фторураци л+лейковорин в 1-й линии химиотерапии метастатического колоректального рака. Фарматека, 2007, 18: 84-86</mixed-citation><mixed-citation xml:lang="en">Zhukova LG, Lichinser MR, Semenov NN, et al. A study of the efficacy and safety of iritene (irinotecan) + fluorouracil + leucovorin in the first-line chemotherapy for metastatic colorectal cancer. Pharmateca, 2007, 18: 84-86.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Гуторов С.Л. Иринотекан в лечении рака толстой кишки. Русский медицинский журнал, 2005,13: 884-887.</mixed-citation><mixed-citation xml:lang="en">Gutorov SL. Irinotecan in the treatment of colon cancer. Russkiy Medicinskiy Zhurnal, 2005.13: 884-887.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Доброва Н.В. Применение кселоды в лечении метастатического колоректального рака. Фарматека, 2010, 17: 44-50.</mixed-citation><mixed-citation xml:lang="en">Dobrova NV. The use of Xeloda in the treatment of metastatic colorectal cancer. Pharmateca, 2010, 17: 44-50.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Доброва Н.В. Применение кселоды в лечении пациентов с метастатическим колоректальным раком. Онкология, 2011, 1: 41-45.</mixed-citation><mixed-citation xml:lang="en">Dobrova NV. The use of Xeloda in the treatment of patients with metastatic colorectal cancer. Onkologia, 2011, 1: 41-45.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Личиницер М.Р., Семенов Н.Н., Пащенко Н.В. Капецитабин (кселода) в лечении колоректального рака и рака молочной железы: новые возможности. Фарматека, 2002, 12: 17-20.</mixed-citation><mixed-citation xml:lang="en">Lichinitser MR, Semenov NN, Paschenko NV. Capecitabine (Xeloda) in the treatment of colorectal cancer and breast cancer: new opportunities. Pharmateca, 2002, 12: 17-20.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Федянин М.Ю., Трякин А.А. Капецитабин и фторурацил в лечении колоректального рака и рака желудка: анализ прямых сравнительных исследований Фарматека, 2011, 17: 20-26.</mixed-citation><mixed-citation xml:lang="en">Fedyanin MYu, Tryakin AA. Capecitabine and fluorouracil in the treatment of colorectal cancer and gastric cancer: an analysis of direct comparative studies Pharmateca, 2011, 17: 20-26.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Федянин М.Ю., Трякин А.А. Капецитабин и флуороурацил в лечении колоректального рака и рака желудка: анализ прямых сравнительных исследований. Клиническая онкология, 2012, 1: 115-118.</mixed-citation><mixed-citation xml:lang="en">Fedyanin MYu, Tryakin AA. Capecitabine and fluorouracil in the treatment of colorectal and gastric cancer: an analysis of direct comparative studies. Klinicheskaya Onkologiya, 2012, 1: 115-118.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Chau I et al. Treatment in advanced colorectal cancer: what when and how? Br. J. Cancer, 2009, 100(11): 1704-1719.</mixed-citation><mixed-citation xml:lang="en">Chau I et al. Treatment in advanced colorectal cancer: what when and how? Br. J. Cancer, 2009, 100(11): 1704-1719.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Tournigand C et al. FOLFIRI followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study. J. Clin. Oncol., 2004, 22(2): 229-237.</mixed-citation><mixed-citation xml:lang="en">Tournigand C et al. FOLFIRI followed by FOLFOX6 or the Reverse Sequence in Advanced Colorectal Cancer: A Randomized GERCOR Study. J. Clin. Oncol., 2004, 22(2): 229-237.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Masi G et al. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann. Surg. 2009, 249: 420-425.</mixed-citation><mixed-citation xml:lang="en">Masi G et al. Long-term outcome of initially unresectable metastatic colorectal cancer patients treated with 5-fluorouracil/leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) followed by radical surgery of metastases. Ann. Surg. 2009, 249: 420-425.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Vasile E et al. A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer. Br. J. Cancer, 2009, 100(11): 1720-1724.</mixed-citation><mixed-citation xml:lang="en">Vasile E et al. A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer. Br. J. Cancer, 2009, 100(11): 1720-1724.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Ychou M et al. Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases. Cancer Chemoth. Pharmacol, 2008, 62(2): 195-201.</mixed-citation><mixed-citation xml:lang="en">Ychou M et al. Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases. Cancer Chemoth. Pharmacol, 2008, 62(2): 195-201.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">https://www.nccn.org/professionals/physician_ gls/default.aspx.</mixed-citation><mixed-citation xml:lang="en">https://www.nccn.org/professionals/physician_ gls/default.aspx.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Grothey A, Sargent D, Goldberg RM et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J ClinOncol, 2004; 22: 1209–14.</mixed-citation><mixed-citation xml:lang="en">Grothey A, Sargent D, Goldberg RM et al. Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J ClinOncol, 2004; 22: 1209–14.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Falcone A et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J. Clin. Oncol, 2007, 25(13): 1670-1676.</mixed-citation><mixed-citation xml:lang="en">Falcone A et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J. Clin. Oncol, 2007, 25(13): 1670-1676.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Vasile E et al. A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer. Br. J. Cancer, 2009, 100(11): 1720-1724.</mixed-citation><mixed-citation xml:lang="en">Vasile E et al. A multicenter phase II study of the combination of oxaliplatin, irinotecan and capecitabine in the first-line treatment of metastatic colorectal cancer. Br. J. Cancer, 2009, 100(11): 1720-1724.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Van Cutsem E et al. Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL trial. J. Clin. Oncol, 2010, 281 (abstr.): 4000.</mixed-citation><mixed-citation xml:lang="en">Van Cutsem E et al. Cetuximab plus FOLFIRI in the treatment of metastatic colorectal cancer (mCRC): the influence of KRAS and BRAF biomarkers on outcome: updated data from the CRYSTAL trial. J. Clin. Oncol, 2010, 281 (abstr.): 4000.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Bokemeyer C et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol., 2009, 27(5): 663-671.</mixed-citation><mixed-citation xml:lang="en">Bokemeyer C et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol., 2009, 27(5): 663-671.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Douillard J-Y, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon J-L, Rother M, Oliner KS, Wolf M, and Gansert J. Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study. Journal of Clinical Oncology, 2010, 28(31): 4697-4705. doi: 10.1200/JCO.2009.27.4860.</mixed-citation><mixed-citation xml:lang="en">Douillard J-Y, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, Błasińska-Morawiec M, Šmakal M, Canon J-L, Rother M, Oliner KS, Wolf M, and Gansert J. Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study. Journal of Clinical Oncology, 2010, 28(31): 4697-4705. doi: 10.1200/JCO.2009.27.4860.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
