2012 개원의와함께하는임상강좌 경희대학교의과대학종양혈액내과학교실 백선경 한국인사망원인 평균수명까지생존시암발생확률
길라잡이 : 개정된가이드라인을중심으로 History of anti-cancer chemotherapy Chabner BA & Roberts TG Jr. Nat Rev 2005 Use standard therapies 2012 개원의와함께하는임상강좌
백선경 : 다양한표적항암제바로알기 Signaling transduction pathways IGF pathway Raf/MAPK pathway EGFR pathway C-MET pathway Akt/mTor pathway Jak/Stat pathway OncogenesHanahan et al. Cell 2000 Ideal target Antigen 1. Should be expressed preferentially on all malignant cells 2. Should not be modulated from the cell surface or secreted into circulation 3. Have some critical biological function Cheson B and Leonard J. N Engl J Med 2008;359:613-626 Nomenclature of Monoclonal Antibodies Ri + tu(m) + xi + mab Beva + ci(r) + zu + mab
길라잡이 : 개정된가이드라인을중심으로 Monoclonal Antibody Sources o xi zu u Mouse Chimeric Humanized Human Nomenclature of monoclonal antibodies Prefix + Target + Source + Suffix Examples: Rituximab : ri +tu(m) + xi + mab trastuzumab: tras + tu +zu + mab bevacizumab: beva + ci + zu + mab Cetuximab: Ce + tu(m) + xi + mab pertuzumab: per + tu(m) + zu + mab Protein kinase inhibitor Name Target cancer Class FDA approval Crizotinib ALK/Met NSCLC Small molecule 2011 Aug (NSCLC with Alk mutation) Dasatinib multiple targets CML Small molecule 2006 Erlotinib Erb1 NSCLC Small molecule 2005 Nov? Gefitinib EGFR NSCLC Small molecule 2003 Imatinib Bcr-Abl CML Small molecule 2001 (CML) Lapatinib Erb1/Erb2 Breast Small molecule 2007 (HER2+ Breast) Nilotinib Bcr-Abl CML Small molecule 2007 Pazopanib VEGFR2/PDGFR/c-kit RCC Small molecule 2009 (RCC) Pegaptanib VEGF OSI/Pfizer RNA Aptamer 2004 (AMD) Ruxolitinib JAK Myelofibrosis Small molecule 2011 (Myelofibrosis) Sorafenib multiple targets RCC Small molecule 2005 Dec (kidney) Sunitinib multiple targets RCC & GIST Small molecule 2006 Jan (RCC & GIST) Vemurafenib BRAF Melanoma Small molecule 2011 Aug (Melanoma) 2012 개원의와함께하는임상강좌
백선경 : 다양한표적항암제바로알기 The Translocation of t(9;22)(q34;q11) in CML Monocytosis in CML Ph+ALL Chronic neutorophilic leukemia variant/ thrombocutosis Faderl S et al. N Engl J Med 1999;341:164-172 Ph+ CML, Ph+ ALL Ph+ CML, Ph+ ALL GIST
길라잡이 : 개정된가이드라인을중심으로 Side effects Severe fluid retention (10%) - eye or lower extremity, lung, heart Px: wt. monitoring, salt restriction Rash Rx. Antihistamine THE LANCET Oncology Vol 4 July 2003 2012 개원의와함께하는임상강좌
백선경 : 다양한표적항암제바로알기 Gefitinib (Iressa) & Erotinib (Tarceva) Small molecule, tyrosine kinase inhibitor NSCLC, adenocarcinoma Predictive marker: EGFR mutation IPASS study, ESMO 2008 Cetuximab and panitumumab Cetuximab (Erbitux) chimeric anti-egfr monoclonal antibody metastatic colorectal cancer and head and neck cancer Panitumumab Fully human IgG2 monoclonal antibody to EGFR
길라잡이 : 개정된가이드라인을중심으로 Adverse events in advanced colorectal cancer patients receiving cetuximab Toxicities Incidence (n=420) All grade Grade ¾ Acneiform rash 90% 8% Asthenia/malaise 48% 10% Nausea 29% 2% Fever 27% <1% Headache 26% 2% Abdominal pain 26% 9% Constipation 26% 2% Diarrhea 25% 2% Vomiting 25% 3% Anorexia 23% 2% Dyspnea 17% 7% Skin rash 2012 개원의와함께하는임상강좌
백선경 : 다양한표적항암제바로알기 Four members of the HER family Cetuximab Panitumumab Trasuzumab Pertuzumab Lapatinib Gefitinib Erotinib Cardiotoxicity of trastzumab Angiogenesis Moses Judah Folkman 1933 2008 founder and director of the Vascular Biology program at Children's Hospital 1971, Folkman's hypothesis that tumors are angiogenesisdependent 1998. Angiostatin, Endostatin
길라잡이 : 개정된가이드라인을중심으로 Three types of angiogenesis inhibitors Combine antiangiogenic agents with standard chemotherapy regimens Incidence of toxicities 2012 개원의와함께하는임상강좌
백선경 : 다양한표적항암제바로알기 Multiple-targeted Therapy Drug Molecular target Status Sorafenib (Nexavar) Sunitinib (Sutene) VEGFR, PDGFR, KIT, FLT3, p38, Raf VEGFR, PDGFR, KIT, FLT3, RET Phase III Phase III Most developed cancer type RCC HCC GIST HCC Pazopanib VEGFR2, PDGFR, KIT Phase III RCC