<?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">rpmj</journal-id><journal-title-group><journal-title xml:lang="ru">Research'n Practical Medicine Journal</journal-title><trans-title-group xml:lang="en"><trans-title>Research and Practical Medicine Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="epub">2410-1893</issn><publisher><publisher-name>"QUASAR", LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.17709/2409-2231-2018-5-3-7</article-id><article-id custom-type="elpub" pub-id-type="custom">rpmj-295</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>Обзоры</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Ингибиторы EGFR в лечении колоректального рака</article-title><trans-title-group xml:lang="en"><trans-title>EGFR inhibitors in the treatment of colorectal cancer</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9816-3614</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Забелин</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Zabelin</surname><given-names>M. В.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Забелин Максим Васильевич - доктор медицинских наук, профессор, заведующий кафедрой онкологии и радиационной медицины Института постдипломного профессионального образования.</p><p>123098, Москва, ул. Маршала Новикова, д. 23</p></bio><bio xml:lang="en"><p>Maxim В. Zabelin - MD, PhD, DSc, head of the department of oncology and radiology, Institute of postgraduate professional education.</p><p>23 Marshala Novikova str., Moscow, 123098</p></bio><email xlink:type="simple">maximzabelin@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8784-8415</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Каприн</surname><given-names>А. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Kaprin</surname><given-names>A. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Каприн Андрей Дмитриевич - академик РАН, доктор медицинских наук, профессор, заведующий кафедрой урологии и оперативной нефрологии с курсом онкоурологии Медицинского института РУДН, генеральный директор НМИЦР.</p><p>249036, Калужская область, Обнинск, ул. Королёва, д. 4</p></bio><bio xml:lang="en"><p>Andrey D. Kaprin - academician of RAS, MD, PhD, DSc, professor, Corr. member of the Russian Academy of Education; Honored Physician of the Russian Federation; General Director of NMRRC, Head of Department of Urology with Course of Urological Oncology, Faculty for Postgraduate Training PFUR.</p><p>4 Koroleva str., Obninsk, Kaluga region, 249036</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0792-6012</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Костин</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kostin</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Костин Андрей Александрович - доктор медицинских наук, профессор, заведующий кафедрой урологии, онкологии и радиологии ФПК МР РУДН, первый заместитель генерального директора НМИЦР.</p><p>249036, Калужская область, Обнинск, ул. Королёва, д. 4</p></bio><bio xml:lang="en"><p>Andrey A. Kostin - MD, PhD, DSc, professor, head of department of urology, oncology and radiology of FAS, Medical institute, RUDN University of Russia; ﬁ rst deputy general director NMRRC MH RF.</p><p>4 Koroleva str., Obninsk, Kaluga region, 249036</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гамеева</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Gameeva</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Гамеева Елена Владимировна - кандидат медицинских наук, заместитель директора по лечебной работе.</p><p>249036, Калужская область, Обнинск, ул. Королёва, д. 4</p></bio><bio xml:lang="en"><p>Elena V. Gameeva - MD, PhD, deputy director for medical work.</p><p>4 Koroleva str., Obninsk, Kaluga region, 249036</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Варламова</surname><given-names>С. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Varlamova</surname><given-names>S. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Варламова Светлана Евгеньевна - ассистент кафедры онкологии и радиационной медицины Института постдипломного профессионального образования.</p><p>123098, Москва, ул. Маршала Новикова, д. 23</p></bio><bio xml:lang="en"><p>Svetlana E. Varlamova - assistant of the department of oncology and radiology, Institute of postgraduate professional education.</p><p>23 Marshala Novikova str., Moscow, 123098</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Институт постдипломного профессионального образования ФГБУ «Государственный научный центр Российской Федерации – Федеральный медицинский биофизический центр им. А.И.Бурназяна» ФМБА России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Institute of postgraduate professional education, State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency (SRC-FMBC)</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>ФГБУ «Национальный медицинский исследовательский центр радиологии» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>10</day><month>09</month><year>2018</year></pub-date><volume>5</volume><issue>3</issue><fpage>77</fpage><lpage>84</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Забелин М.В., Каприн А.Д., Костин А.А., Гамеева Е.В., Варламова С.Е., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Забелин М.В., Каприн А.Д., Костин А.А., Гамеева Е.В., Варламова С.Е.</copyright-holder><copyright-holder xml:lang="en">Zabelin M.В., Kaprin A.D., Kostin A.A., Gameeva E.V., Varlamova S.E.</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.rpmj.ru/rpmj/article/view/295">https://www.rpmj.ru/rpmj/article/view/295</self-uri><abstract><p>В данной статье рассматриваются вопросы применения ингибиторов EGFR в лечении больных колоректальным раком, механизмы их действия, специфичные проявления токсичности. Приведен обзор современных данных литературы по использованию как одобренных для клинического применения (цетуксимаб, панитумумаб), так и находящихся на этапе клинических исследований анти-EGFR антител. Ингибиторы EGFR – одна из основных групп таргетных препаратов, использующихся для лечения больных колоректальным раком. Отдельно обсуждена корреляция между токсичностью и эффективностью данных препаратов. Область их применения ограничена лечением диссеминированных форм заболевания, однако в перспективе число доступных анти-EGFR антител может вырасти, рассматривается возможность их применения в новых условиях, в том числе в рамках курсов химиолучевой терапии.</p></abstract><trans-abstract xml:lang="en"><p>This ar cle discusses the use of EGFR inhibitors in the treatment of pa ents with colorectal cancer. The mechanisms of their ac on, speciﬁ c manifesta ons of toxicity are considered. A review of current literature data on the use of both approved for clinical use (cetuximab, panitumumab) and an -EGFR an bodies at the stage of clinical trials is presented. EGFR inhibitors are one of the main groups of targeted drugs used to treat pa ents with colorectal cancer. The correla on between toxicity and eﬃ  cacy of these drugs is discussed separately. The scope of their applica on is limited to the treatment of disseminated forms of the disease, but in the future the number of available an -EGFR an bodies may grow, the possibility of their use in new condi ons, including in the framework of chemoradiotherapy.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>колоректальный рак</kwd><kwd>рак прямой кишки</kwd><kwd>таргетная терапия</kwd><kwd>ингибиторы EGFR</kwd></kwd-group><kwd-group xml:lang="en"><kwd>colorectal cancer</kwd><kwd>rectal cancer</kwd><kwd>targeted therapy</kwd><kwd>EGFR inhibitors</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">Kiyota A, Shintani S, Mihara M, Nakahara Y, Ueyama Y, Matsumura T, et al. Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27(KIP1) and p15(INK4B) and induces G1 arrest in oral squamous carcinoma cell lines. Oncology. 2002;63(1):92-8. DOI: 10.1159/000065726</mixed-citation><mixed-citation xml:lang="en">Kiyota A, Shintani S, Mihara M, Nakahara Y, Ueyama Y, Matsumura T, et al. Anti-epidermal growth factor receptor monoclonal antibody 225 upregulates p27(KIP1) and p15(INK4B) and induces G1 arrest in oral squamous carcinoma cell lines. Oncology. 2002;63(1):92-8. DOI: 10.1159/000065726</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Iannello A., Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the eﬃcacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005 Dec;24(4):48799. DOI: 10.1007/s10555-005-6192-2</mixed-citation><mixed-citation xml:lang="en">Iannello A., Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the eﬃcacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005 Dec;24(4):48799. DOI: 10.1007/s10555-005-6192-2</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer. 2007 Feb 15;120(4):781-7. DOI: 10.1002/ijc.22370</mixed-citation><mixed-citation xml:lang="en">Kawaguchi Y, Kono K, Mimura K, Sugai H, Akaike H, Fujii H. Cetuximab induce antibody-dependent cellular cytotoxicity against EGFR-expressing esophageal squamous cell carcinoma. Int J Cancer. 2007 Feb 15;120(4):781-7. DOI: 10.1002/ijc.22370</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Kurai J, Chikumi H, Hashimoto K, Yamaguchi K, Yamasaki A, Sako T, et al. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res. 2007 Mar 1;13(5):1552-61. DOI: 10.1158/1078-0432.CCR-06-1726</mixed-citation><mixed-citation xml:lang="en">Kurai J, Chikumi H, Hashimoto K, Yamaguchi K, Yamasaki A, Sako T, et al. Antibody-dependent cellular cytotoxicity mediated by cetuximab against lung cancer cell lines. Clin Cancer Res. 2007 Mar 1;13(5):1552-61. DOI: 10.1158/1078-0432.CCR-06-1726</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Трякин А.А. Таргетная терапия колоректального рака, рака желудка и поджелудочной железы. Практическая онкология. 2010;11(3):143-150.</mixed-citation><mixed-citation xml:lang="en">Tryakin A.A. Targetnaya terapiya kolorektal’nogo raka, raka zheludka i podzheludochnoi zhelezy. Practical Oncology. 2010;11(3):143-150. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Федянин М.Ю., Трякин А.А., Тюляндин С.А. Потенциальные предикторы эффективности анти-EGFR-терапии при метастатическом раке толстой кишки. Онкологическая колопроктология. 2013;2:21-30.</mixed-citation><mixed-citation xml:lang="en">Fedyanin MYu, Tryakin AA, Tjulandin SA. Potential predictors of anti-EGFR-treatment eﬃcacy in metastatic colorectal cancer. Oncological Coloproctology. 2013;2:21-30. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Артамонова Е.В. Цетуксимаб в терапии метастатического рака толстой кишки: кожная токсичность и пути решения проблемы. Онкологическая колопроктология. 2011;3:21-28.</mixed-citation><mixed-citation xml:lang="en">Artamonova EV. Cetuximab in metastatic colon cancer treatment: skin toxicity and solutions to this problem. Oncological Coloproctology. 2011;3:21-28. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Воронцова К.А., Черноглазова Е.В., Вышинская Г.В. Таргетные препараты во второй линии противоопухолевой терапии диссеминированного колоректального рака. Медицинский совет. 2015;8:91-92.</mixed-citation><mixed-citation xml:lang="en">Vorontsova KA, Chernoglazova EV, Vyshinskaya GV. Targeted drugs in the second line anticancer therapy of disseminated colorectal cancer. Meditsinskiy Sovet (Medical Council). 2015;8. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Бесова Н.С. Эволюция лекарственной терапии диссеминированного колоректального рака. Таргетная терапия. Эффективная фармакотерапия. 2011;25:12-21.</mixed-citation><mixed-citation xml:lang="en">Besova NS. Evolyutsiya lekarstvennoi terapii disseminirovannogo kolorektal’nogo raka. Targetnaya terapiya. Eﬀective Pharmacotherapy. 2011;25:12-21. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Федянин М.Ю., Трякин А.А., Тюляндин С.А. Таргетные препараты в терапии рака толстой кишки. Эффективная фармакотерапия. 2012;36:30-37.</mixed-citation><mixed-citation xml:lang="en">Fedyanin MYu, Tryakin AA, Tyulyandin SA. Targetnye preparaty v terapii raka tolstoi kishki. Eﬀective Pharmacotherapy. 2012;36:30-37. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Кит О.И., Кириченко Е.Ю., Новикова И.А., Максимов А.Ю., Филиппова С.Ю., Гранкина А.Щ., Златник Е.Ю. Иммунотерапия колоректального рака: современное состояние и перспективы (обзор). Современные технологии в медицине. 2017;9(3):138-150 DOI: 10.17691/stm2017.9.3.18.</mixed-citation><mixed-citation xml:lang="en">Kit OI, Kirichenko EY, Novikova IA, Maksimov AY, Filippova SY, Grankina AO, Zlatnik EY. Colorectal Cancer Immunotherapy: Current State and Prospects (Review). Modern Technologies in Medicine. 2017;9(3):138-150. DOI: 10.17691/stm2017.9.3.18 (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Доброва Н. Цетуксимаб в лечении метастатического колоректального рака. Эффективная фармакотерапия. 2012;35:24-9.</mixed-citation><mixed-citation xml:lang="en">Dobrova NS. Tsetuksimab v lechenii metastaticheskogo kolorektal’nogo raka. Eﬀective Pharmacotherapy. 2012;35:24-9. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Владимирова Л.Ю., Абрамова Н.А., Сторожакова А.Э. Таргетная терапия анти–EGFR моноклональными антителами в лечении колоректального рака. Злокачественные опухоли. 2016; Спецвыпуск 1_97-91. DOI: 10.18027/2224-5057-20164s1-87-91</mixed-citation><mixed-citation xml:lang="en">Vladimirova LYu, Abramova NA, Storozhakova AE. Targetnaya terapiya anti–EGFR monoklonal’nymi antitelami v lechenii kolorektal’nogo raka. Malignant Tumoursis. 2016;S1:87-91. DOI: 10.18027/2224-5057-2016-4s1-87-91 (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">14. Горчаков С.В., Правосудов И.В., Васильев С.В., Олейник В.В., Оношко М.В., Попов Д.Е., и др. Современные подходы к лечению больных колоректальным раком с метастазами в печень: обзор литературы. Вестник Санкт-Петербургского университета. Серия 11. Медицина. 2015;3:55-68.</mixed-citation><mixed-citation xml:lang="en">Gorchakov SV, Pravosudov IV, Vasiljev SV, Oleynik VV, Onoshko MV, Popov DE, et al. Modern approach to treatment of colorectal cancer patients with liver metastases (literature review). Vestnik SPbSU. Medicine. 2015;3:55-68. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Venook A, Niedzwiecki D, Hollis D, Sutherland S, Goldberg R, Alberts S, et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX)±cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. Journal of Clinical Oncology. 2006;24(18):3509.</mixed-citation><mixed-citation xml:lang="en">Venook A, Niedzwiecki D, Hollis D, Sutherland S, Goldberg R, Alberts S, et al. Phase III study of irinotecan/5FU/LV (FOLFIRI) or oxaliplatin/5FU/LV (FOLFOX)±cetuximab for patients (pts) with untreated metastatic adenocarcinoma of the colon or rectum (MCRC): CALGB 80203 preliminary results. Journal of Clinical Oncology. 2006;24(18):3509.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Van Cutsem E, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J, et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. Journal of Clinical Oncology. 2007;25(18):4000.</mixed-citation><mixed-citation xml:lang="en">Van Cutsem E, Nowacki M, Lang I, Cascinu S, Shchepotin I, Maurel J, et al. Randomized phase III study of irinotecan and 5-FU/FA with or without cetuximab in the first-line treatment of patients with metastatic colorectal cancer (mCRC): The CRYSTAL trial. Journal of Clinical Oncology. 2007;25(18):4000.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. DOI: 10.1200/JCO.2010.33.5091.</mixed-citation><mixed-citation xml:lang="en">Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, et al. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. DOI: 10.1200/JCO.2010.33.5091.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Феоктистова П.С., Загинайко А.В., Карасева В.В., Хайленко В.А. Таргетная терапия метастатического колоректального рака. Здравоохранение Югры: опыт и инновации. 2016;Спецвыпуск:76-84.</mixed-citation><mixed-citation xml:lang="en">Feoktistova P.S., Zaginaiko A.V., Karaseva V.V., Khailenko V.A. Targetnaya terapiya metastaticheskogo kolorektal’nogo raka. Zdravookhranenie Yugry: opyt i innovatsii. 2016;S1:76-84. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 10;26(14):2311-9. DOI: 10.1200/JCO.2007.13.1193</mixed-citation><mixed-citation xml:lang="en">Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, et al. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 10;26(14):2311-9. DOI: 10.1200/JCO.2007.13.1193</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Goldberg R, Sargent D, Thibodeau S, Mahoney M, Shields A, Chan E, et al. Adjuvant mFOLFOX6 plus or minus cetuximab (Cmab) in patients (pts) with KRAS mutant (m) resected stage III colon cancer (CC): NCCTG Intergroup Phase III Trial N0147. Journal of Clinical Oncology. 2010;28(1):3508.</mixed-citation><mixed-citation xml:lang="en">Goldberg R, Sargent D, Thibodeau S, Mahoney M, Shields A, Chan E, et al. Adjuvant mFOLFOX6 plus or minus cetuximab (Cmab) in patients (pts) with KRAS mutant (m) resected stage III colon cancer (CC): NCCTG Intergroup Phase III Trial N0147. Journal of Clinical Oncology. 2010;28(1):3508.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. 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. J Clin Oncol. 2010 Nov 1;28(31):4697-705. DOI: 10.1200/JCO.2009.27.4860.</mixed-citation><mixed-citation xml:lang="en">Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. 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. J Clin Oncol. 2010 Nov 1;28(31):4697-705. DOI: 10.1200/</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. DOI: 10.1056/NEJMoa1305275.</mixed-citation><mixed-citation xml:lang="en">Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal Cancer. N Engl J Med. 2013 Sep 12;369(11):102334. DOI: 10.1056/NEJMoa1305275.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64. DOI: 10.1200/JCO.2006.08.1620</mixed-citation><mixed-citation xml:lang="en">Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, et al. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64. DOI: 10.1200/JCO.2006.08.1620</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Argiles G, Dienstmann R, Elez E, Tabernero J. Panitumumab: a summary of clinical development in colorectal cancer and future directions. Future Oncol. 2012 Apr;8(4):373-89. DOI: 10.2217/fon.12.20</mixed-citation><mixed-citation xml:lang="en">Argiles G, Dienstmann R, Elez E, Tabernero J. Panitumumab: a summary of clinical development in colorectal cancer and future directions. Future Oncol. 2012 Apr;8(4):373-89. DOI: 10.2217/fon.12.20</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Jin T, Zhu Y, Luo J-L, Zhou N, Li D-C, Ju H-X, et al. Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer. Int J Colorectal Dis. 2015 Mar;30(3):337-45. DOI: 10.1007/s00384014-2097-2.</mixed-citation><mixed-citation xml:lang="en">Jin T, Zhu Y, Luo J-L, Zhou N, Li D-C, Ju H-X, et al. Prospective phase II trial of nimotuzumab in combination with radiotherapy and concurrent capecitabine in locally advanced rectal cancer. Int J Colorectal Dis. 2015 Mar;30(3):337-45. DOI: 10.1007/s00384014-2097-2.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Zhou J, Shen L, Gao J. A dose escalation study of nimotuzumab plus irinotecan as second-line treatment in metastatic colorectal cancer with wild-type K-ras. Book A dose escalation study of nimotuzumab plus irinotecan as second-line treatment in metastatic colorectal cancer with wild-type K-ras. EditorAmerican Society of Clinical Oncology, 2012.</mixed-citation><mixed-citation xml:lang="en">Zhou J, Shen L, Gao J. A dose escalation study of nimotuzumab plus irinotecan as second-line treatment in metastatic colorectal cancer with wild-type K-ras. Book A dose escalation study of nimotuzumab plus irinotecan as second-line treatment in metastatic colorectal cancer with wild-type K-ras. EditorAmerican Society of Clinical Oncology, 2012.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Elez E, Hendlisz A, Delaunoit T, Sastre J, Cervantes A, Varea R, et al. Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer. Br J Cancer. 2016 Feb 16;114(4):372-80. DOI: 10.1038/bjc.2015.480</mixed-citation><mixed-citation xml:lang="en">Elez E, Hendlisz A, Delaunoit T, Sastre J, Cervantes A, Varea R, et al. Phase II study of necitumumab plus modified FOLFOX6 as first-line treatment in patients with locally advanced or metastatic colorectal cancer. Br J Cancer. 2016 Feb 16;114(4):372-80. DOI: 10.1038/bjc.2015.480</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Rosello S, et al. Safety and Activity of the Firstin-Class Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Cancer Discov. 2015 Jun;5(6):598609. DOI: 10.1158/2159-8290.CD-14-1432</mixed-citation><mixed-citation xml:lang="en">Dienstmann R, Patnaik A, Garcia-Carbonero R, Cervantes A, Benavent M, Rosello S, et al. Safety and Activity of the First-inClass Sym004 Anti-EGFR Antibody Mixture in Patients with Refractory Colorectal Cancer. Cancer Discov. 2015 Jun;5(6):598609. DOI: 10.1158/2159-8290.CD-14-1432</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Lee KW, Oh D-Y, Han S-W, Kim JW, Shin J-W, Jo S-J,et al. A firstin-human phase 1 study of GC1118, a novel monoclonal antibody inhibiting epidermal growth factor receptor (EGFR), in patients with advanced solid tumors. Book A first-in-human phase 1 study of GC1118, a novel monoclonal antibody inhibiting epidermal growth factor receptor (EGFR), in patients with advanced solid tumors. EditorAmerican Society of Clinical Oncology, 2016.</mixed-citation><mixed-citation xml:lang="en">Lee KW, Oh D-Y, Han S-W, Kim JW, Shin J-W, Jo S-J,et al. A firstin-human phase 1 study of GC1118, a novel monoclonal antibody inhibiting epidermal growth factor receptor (EGFR), in patients with advanced solid tumors. Book A first-in-human phase 1 study of GC1118, a novel monoclonal antibody inhibiting epidermal growth factor receptor (EGFR), in patients with advanced solid tumors / EditorAmerican Society of Clinical Oncology, 2016.</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>
