Афлиберцепт: в фокусе внимания побочные явления
Аннотация
В качестве второй линии терапии больных метастатическим раком толстой кишки зарегистрирован новый антиангиогенный препарат афлиберцепт, применение которого с режимом FOLFIRI значимо уменьшает риск прогрессирования болезни (ОР = 0,758, р = 0,00007). В то же время добавление афлиберцепта в исследовании VELOUR привело к развитию у 83,5% пациентов нежелательных явлений 3–4-й степени тяжести, включая не только осложнения, характерные для антиангиогенных препаратов, но и случаи диареи и нейтропении. В связи с этим онкологу необходимо разбираться в патогенезе, способах профилактики и лечения осложнений, связанных с применением афлиберцепта. Именно этим аспектам и посвящен данный обзор.
Об авторе
М. Ю. Федянин
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России
Россия
Россия
Доктор медицинских наук
Москва
Список литературы
1. Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol, 2012 Oct 1, 30(28): 3499-506.
2. Folprecht G, Pericay C, Saunders MP, et al. Oxaliplatin and 5-FU/folinic acid (modified FOLFOX6) with or without aflibercept in firstline treatment of patients with metastatic colorectal cancer: the AFFIRM study. Ann Oncol, 2016 Apr 18. pii: mdw176. [Epub ahead of print].
3. Enzinger PC, McCleary NJ, Zheng H, et al. Multicenter double-blind randomized phase II: FOLFOX + ziv-aflibercept/placebo for patients (pts) with chemo-naive metastatic esophagogastric adenocarcinoma (MEGA). J Clin Oncol, 2016, 34(suppl 4S, abstr 4).
4. Chiron MVP, Lejeune P, Demers B, et al. Synergistic activity of aflibercept (VEGF Trap) in combination with 5-fluorouracil and irinotecan in preclinical tumor models. Proceeding from AACR-NCI-EORTC: Molecular Targets and Cancer Therapeutics, Abstract A13, 2007, San Francisco, Calif, USA.
5. Presta LG, Chen H, O’Connor SJ, et al. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res, 1997, 57: 4593-9.
6. Dikov MM, Ohm JE, Ray N, et al. Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation. J Immunol, 2005, 174: 215-22.
7. Papadopoulos N, Martin J, Ruan Q, et al. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis, 2012, 15: 171-85.
8. Chiron M, Bagley RG, Pollard J, et al. Differential antitumor activity of aflibercept and bevacizumab in patient-derived xenograft models of colorectal cancer. Mol Cancer Ther, 2014, 13(6): 1636-44.
9. Lu D, Shen J, Vil MD et al. Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J Biol Chem, 2003, 278: 43496-507.
10. Miao HQ, Hu K, Jimenez X, et al. Potent neutralization of VEGF biological activities with a fully human antibody Fab fragment directed against VEGF receptor 2. Biochem Biophys Res Commun, 2006, 345: 438-45.
11. Wilhelm SM, Dumas J, Adnane L, et al. Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer, 2011, 129: 245-55.
12. Chau I, Joulain F, Iqbal SU and Bridgewater J. A VELOUR post hoc subset analysis: prognostic groups and treatment outcomes in patients with metastatic colorectal cancer treated with aflibercept and FOLFIRI. BMC Cancer, 2014, 14: 605 doi: 10.1186/1471-2407-14-605.
13. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update summary. Journal of Clinical Oncology, 2017 October 1, 35(28): 3240-3261.
14. Strimpakos, A.S., Syrigos, K.N., and Saif, M.W. Pharmacogenetics and biomarkers in colorectal cancer. Pharmacogenomics J, 2009, 9: 147–160.
15. Scripture CD, Figg WD. Drug interactions in cancer therapy. Nature Reviews Cancer, 2006, 6: 546-558.
16. FDA instruction of irinotecan (https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020571s048lbl.pdf).
17. Olver IN. The MASCC Textbook of Cancer Supportive Care and Survivorship. New York: Springer, 2011.
18. Mourad JJ, des Guetz G, Debbabi H, Levy BI. Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann Oncol, 2008, 19: 927-934.
19. Краткая характеристика лекарственного средства Залтрап. Рег. № ЛП-002534.
20. Eremina V, Jefferson JA, Kowalewska J. VEGF inhibition and renal thrombotic microangiopathy. N Eng J Med, 2008, 358: 1129-1136.
21. Kumpf VJ. Pharmacologic management of diarrhea in patients with short bowel syndrome. JPEN J Parenter Enteral Nutr, 2014 May, 38(1 Suppl): 38S-44S.
22. Benson AB 3rd, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol, 2004 Jul 15, 22(14): 2918-26.
23. Saavedra E, Hollebecque A, Soria JC, Hartl DM. Dysphonia induced by anti-angiogenic compounds. Invest New Drugs, 2014 Aug, 32(4): 774-82
24. Lockhart AC, Rothenberg ML, Dupont J, Cooper W, Chevalier P, Sternas L, et al. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol, 2010, 28: 207–14.
25. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol, 2007, 25(12): 1539-44.
26. Lam JYC, Ng MCH. Posterior Reversible Encephalopathy Syndrome and Anti-Angiogenic Therapy. Proceedings of Singapore Healthcare, 2014, 23(3): 241-245.
27. Qi WX, Shen F, Qing Z, Xiao-Mao G.Risk of gastrointestinal perforation in cancer patients treated with aflibercept: a systematic review and meta-analysis. Tumour Biol, 2014 Nov, 35(11): 10715-22.
Для цитирования:
Федянин М.Ю. Афлиберцепт: в фокусе внимания побочные явления. Медицинский Совет. 2018;(10):18-26. https://doi.org/10.21518/2079-701X-2018-10-18-26
For citation:
Fedyanin M.Yu. Aflibercept: side effects in focus. Meditsinskiy sovet = Medical Council. 2018;(10):18-26. (In Russ.) https://doi.org/10.21518/2079-701X-2018-10-18-26
Просмотров: 581
Послать статью по эл. почте 
