항암제분류
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1 항암제의분류와약리작용 국립암센터약제부 전혜원
2 항암제의분류 Cytotoxic antineoplastics Alkylating agents Topoisomerase inhibitors Antimetabolites Microtubules inhibitors (Mitotic inhibitor) Hormonal agents Molecular targeted therapy Monoclonal Antibody Small molecule Immune therapy & Others.. in oncology Thalidomide, CTLA-4, PD-L1, and others
3 1. Cytotoxic antineoplastics
4 Cell cycle 과항암제의작용
5 1) Alkylating agents A. Nitrogen mustards Cyclophosphamide Ifosfamide Melphalan Chlorambucil Mechlorethamine B. Nitrosourea Carmustine Nimustine Lomustine Streptozocin C. Platinum analogues Cisplatin Carboplatin Oxaliplatin D. Others Ethylemines Thiotepa Alkylsufonate Busulfan Triazenes Dacarbazine Temozolomide
![1) Alkylating agents 작용기전 Formation of a positively charged ethylene immonium ion [-N-CH2CH2-] + => binds to electron rich nucleophilic sites](/docs-images/80/81483510/images/6-3.jpg "Cytotoxic effect Inhibition of DNA replication and transcription Mispairing of DNA Strand breakage Toxicity Myelosuppression Infertility Secondary")
6 1) Alkylating agents 작용기전 Formation of a positively charged ethylene immonium ion [-N-CH2CH2-] + => binds to electron rich nucleophilic sites Cytotoxic effect Inhibition of DNA replication and transcription Mispairing of DNA Strand breakage Toxicity Myelosuppression Infertility Secondary malignancy
7 Alkylating Agents A. Nitrogen mustards Cyclophosphamide Ifosfamide ( 사진 ) Melphalan Chlorambucil Mechlorethamine 적응증 NHL, HD, Leukemia, MM, BMT-conditioning, breast cancer, neuroblastoma and a variety other tumor Lung cancer, HD, NHL, Leukemia, breast cancer, testicular cancer, sarcomas MM, Ovrian cancer CLL, NHL, HD HD 부작용 Hemorrhagic cystitis N/V, alopecia, SIADH (> 50mg/kg), 2 nd malignancy, infertility Hemorrhagic cystitis (mesna 함께투여 )
8 Alkylating Agents B. Nitrosoureas 최근생산되는약제없음 적응증 부작용 Carmustine (BCNU) Brain tumor, HD, NHL, MM Delayed myelosuppression Severe N/V Pulmonary toxicity Nimustine (ACNU) Brain tumor, HD, NHL Delayed myelosuppression Lomustine (CCNU) Brain tumor, HD Delayed myelosuppression
9 Alkylating Agents C. Platinum analogues Cisplatin ( 사진 ) Carboplatin 적응증 Testicular cancer, ovarian cancer, head & neck cancer, lung cancer, esophageal cancer, cervical cancer, gastric cancer, or other cancers Ovarian cancer, lung cancer, bladder cancer, head & neck cancer, and testicular cancers 부작용 Severe nausea/vomiting (Acute, delayed) Nephrotoxicity; hydration Peripheral neuropathy Myelosuppression (Thrombocytopenia) Oxaliplatin 용량계산 : Calvert formula Dose=Target AUC x (CrCl+25) Colorectal cancer, gastric cancer Peripheral neuropathy (Cold triggered or aggravated)
10 Alkylating Agents D. Other alkylating agents Thiotepa 적응증 Breast cancer, ovary cancer, bladder cancer, lymphoma 부작용 Busulfan AML, CML, BMT Pulmonary toxicity (rare) Hyperpigmentation (High dose) Seizure, N/V, SOS Dacarbazine Melanoma, HD Nausea/Vomiting (N/V) Temozolomide ( 사진 ) Brain tumor N/V ( 취침전투약 ) ( 연하곤란환자 : 산성에서안정하므로사과쥬스에섞어서 L- tube 가능 )
11 2) Topoisomerase inhibitors Topoisomerase Regulation of DNA supercoiling Topoisomerase inhibitors 종류 Topoisomerase I inhibitor : Irinotecan, topotecan Topoisomerase II inhibitor : Anthracyclines, Epiphodophyllotoxins
12 2) Topoisomerase inhibitors Irinotecan( 사진 ), topotecan Topoisomerase I : DNA single strand breakage and religation, removal of supercoiling of DNA Topoisomerase I inhibitor: cleavable complex 상태로안정화시킴으로써 single stranded DNA break 를유도
13 2) Topoisomerase inhibitors Anthracycline, epipodophyllotoxins Topoisomerase II : DNA double strand cleaving and resealing, introduction of supercoiling in DNA Topoisomerase II inhibitor: preventing the ligation of DNA during replication Anthracycline Daunorubicin Doxorubicin ( 사진 ) Idarubicin Epirubicin Epipodophyllotoxins Etoposide Teniposide 작용기전 DNA intercalation Inhibition of Topoisomerase II free radical formation Inhibition of Topoisomerase II
14 2) Topoisomerase inhibitors 적응증 부작용 Daunorubicin Leukemia % Cardiotoxicity at Doxorubicin Cumulative Dose = 5% risk at 450 mg/m 2 Idarubicin Epirubicin Liposomal Doxorubicin ( 사진 ) Various solid tumors including breast cancer, ovarian caner lymphoma, leukemia Acute leukemia, lymphoma, HD Breast cancer AIDS-related Kaposi sarcoma, Multiple myeloma, advanced Ovarian cancer Cardiotoxicity, Palmarplantar erythrodysesthesia Etoposide Testicular cancer, Lung cancer Hypotension Teniposide HD, NHL, ALL, Bladder cancer Irinotecan Colorectal cancer, lung cancer Diarrhea (SN-38) Topotecan Ovarian cancer, SCLC
15 3) Antimetabolites 작용기전 Amino acid, DNA, RNA 등체내 natural compound 와구조적으로유사하여생합성시 enzyme 의 binding site 에서경쟁하거나 DNA 나 RNA 에 incorporation 되어 cytotoxic effect 를나타냄 분류 A. Folate antagonist B. Pyrimidine analogue C. Purine analogue
16 Antimetabolite A. Folate antagonist 작용기전적응증비고 Methotrexate (MTX) ( 사진 ) Dihydrofolate reductase (DHFR) 저해하여 thymidylate, purine 합성을저해 Triphoblastic neoplasm, leukemia, breast, head, lung cancer Mucositis, renal dysfunction, hepatotoxicity * Leucovorin rescue Pemetrexed Mutitargeted antifolate : TS, DHFR, GARFT 등효소모두저해 Malignant pleural mesothelioma, NSCLC Co-med: Folate, Vit B12, dexa
17 Antimetabolite Pemetrexed (Alimta ) Mutitargeted antifolate TS, DHFR, GARFT Co-medication 부작용을줄이기위해투여 (rash, myelosuppression) Folate mcg/day pemetrexed 투여 1 주일전부터투여종료 3 주후까지 Vit B mcg pemetrexed 투여 1 주일전부터 9 주간격으로 IM Dexamethasone 4mg bid, pemetrexed 투여전날, 투여당일, 투여다음날
18 Antimetabolite 20mg B. Pyrimidine analogue 25mg Cytarabine (Ara-C) Gemcitabine Fluorouracil (5-FU) Capecitabine ( 사진 ) TS-1 ( 사진 ) 작용기전적응증부작용 DNA polymerase를저해 Leukemia 고용량시 CNS toxicity, conjunctivitis Ribonucleotide reductase 를 저해, DNA incorporation Thymidylate synthetase (TS: dump dtmp ) 를저해 * leucovorin(folinic acid) 사용 5-FU 의 prodrug (3 단계를거쳐 5-FU 로변환, 마지막단계에서 Thymidine phsophrylase (TP) 에의해변환되는데이는정상조직보다암세포에서많음 ) Tegafur (5-FU prodrug), Gemeracil, Oteracil Pancreatic cancer, NSCLC Colon, breast, rectal, gastric, pancreatic cancer Colon, breast, rectal, gastric cancer Gastric, colon, rectal cancer Flu-like syndrome Diarrhea, skin discoloration Hand-foot syndrome Diarrhea Diarrhea, mucositis, Hand-foot syndrome Azacitidine Vidaza 골수이형성증후군 (MDS) N/V/D/C, HA, edema Decitabine Dacogen MDS 상동
19 Antimetabolite C. Purine analogue 작용기전적응증비고 Mercaptopurine (6-MP) Purine synthesis 저해 Leukemia Hepatotoxicity Thioguanine (6-TG) Guanine 과경쟁하여 purine synthesis 저해 Leukemia Hepatotoxicity Fludarabine DNA polymerase, ribonucleotide reductase 저해 CLL
20 4) Microtubule inhibitors 작용기전 Microtubule 의 polymerization, depolymerization 을억제하여 M- phase 세포분열을억제 Vinca alkaloids Tubulin 에결합하여 microtubule 을형성저해 Vincristine, vinblastine, vinorelbine 척수강내투여금기 Taxanes Microtubule 에결합하여 depolymerization 을저해 Paclitaxel, docetaxel
21 4) Microtubule inhibitors Vincristine 적응증 Leukemia, HD, neuroblatoma, lymphoma Neurotoxicity 부작용 Constipation, paralytic ileus Vinblastine HD, breast cancer, testicular cancer, Leukopenia, Neurotoxicity germ -cell tumor Thrombocytopenia Vinorelbine NSCLC, breast cancer Neurotoxicity, Constipation Docetaxel (Taxotere ) ( 사진 ) Paclitaxel (Taxol ) Ixabepilone (Ixempra ) Eribuline (Halaven ) Cabazitaxel (Zevtana ) Breast cancer, NSCLC, Ovarian cancer, Head & Neck cancer, gastric cancer Breast cancer, lung cancer, ovarian cancer, gastric cancer Breast cancer (± Xeloda ) Breast cancer hormone-refractory prostate cancer (+Prednisolone) Leukopenia, peripheral edema, alopecia, peripheral neuropathy, hypersensitivity Leukopenia, hypersensitivity, alopecia, peripheral neuropathy Leukopenia, peripheral edema, alopecia, peripheral neuropathy, N/V/D Leukopenia, alopecia, peripheral neuropathy Leukopenia, alopecia, peripheral neuropathy
22 문제 1. 다음중골수억제부작용이제일심각한약제는? A. Irinotecan B. Carboplatin C. Docetaxel D. Busulfan : alkylating agent, BMT
23 2. Hormonal agents
24 Hormonal therapy : breast cancer Premenopausal LHRH agonist Hypothalamus Pre / Postmenopausal LHRH X Pituitary ACTH FSH, LH Adrenal gland Ovary Androgen Estrogens Progesterone Antiestrogen X Aromatase inhibitor X X Estrogen
25 1) Antiestrogen: Tamoxifen 작용기전 Target specific action Antiestrogenic : breast, vagina, CNS Estrogenic : endometrium, bone, lipid SERM Tamoxifen( 사진 ) : 20mg/day 적응증 Hormone-positive breast cancer SERDs Fulvestrant : 500mg/q28day (IM) Toremifene : 60mg/day (FDA 2009) SERM : selective estrogen receptor modulator SERD : selective estrogen receptor downregulator 부작용 Hot flash, nausea, vaginal bleeding, thromboembolism, endometrial cancer
26 2) Aromatase inhibitor 작용기전 Estrone, estradiol 생성에작용하는 aromatase 를차단 Nonsteroidal Anastrozole ( 사진 ) : 1mg/day Steroidal Exemestane : 25mg/day Letrozole : 2.5mg/day 적응증 : Hormone-positive breast cancer, 폐경후 부작용 GI disturbance, hot flashes, Musculoskeletal symptoms, thromboembolic disorders
27 Hormonal therapy : Prostate cancer LHRH agonists Goserelin( 졸라덱스 *) Leuprorelin( 루크린 *) Triptorelin( 디페렐린 *) Produces ~10% of testosterone Orchidectomy ( 고환절제술 ) Produces ~90% of testosterone antiandrogen Antiandrogens Flutamide( 유렉신 *) Bicalutamide( 카소덱스 *)
28 3) LHRH agonist 작용기전 LH-RH analog 제제로서 pituitary gonadotropin secretion 억제 Goserelin (Zoladex ) Leuprorelin (Leucrin ) Triptorelin (Diphereline ) 3.6mg/q 1months 3.75mg/q 1months mg/q 3months 11.25mg/q 3months 11.25mg/q 3months - 30mg/q 6months - 적응증 Prostate cancer, breast cancer 부작용 Tumor flare (bone pain 등 ), Hot flashes, impotence, injection site reaction, bone loss
29 4) Antiandrogen 작용기전 Androgen receptor competitive inhibitor DHT receptor complex 형성을저해하여 androgen mediated action 을방해 종류 Flutamide, bicalutamide, nilutamide 적응증 : prostate cancer 부작용 Gynecomastia, hot flashes, GI disturbance(nausea, diarrhea), LFT 상승, visual disturbance
30 4) Antiandrogen Abiraterone acetate (Zytiga*) CYP17A1 의비가역적저해제 ( 고환, 부신, 전립선종양조직 ) 1000mg/day joint swelling or discomfort, hypokalemia, edema, Enzalutamide (Xtandi*) AR inhibitor 160mg/day Hot flush, hypertension, insomnia, edema, seizure... 이전에도세탁셀을포함한화학요법을받았던전이성거세저항성전립선암환자의치료
31 문제 2. 다음중 tumor flare 에대한우려없이단독요법으로사용가능한약제는? A. Degarelix B. Leuprolide C. Goserelin D. Triptorelin Firmagon is a GnRH receptor antagonist indicated for treatment of patients with advanced prostate cancer.
32 약제부고위험약물
33 약제부고위험약물
34 3. Molecular targeted therapy
35 Molecular targeted therapy R R Antibody-Based Membrane K K ATP Small Molecule Inhibitor Lung Prostate Breast Ovary Gastric Colon
36 Molecular targeted therapy (1) Mechanism of Action: 단클론항체 A~D 기전 A. 세포사멸 B. ADCC(Antibodydependent cellmediated cytotoxicity) C. 보체연쇄반응 D. 신생혈관생성억제
37 Targets Drugs Target HER CD20 CD30 CD33 CD52 VEGF Bcl-abl Multi- Monoclonal Abs Cetuximab, Panitumumab(HER-1) Trastuzumab,Pertuzumab,T-DM1(HER-2) Rituximab, Ibritumomab tiuxetan + Y-90 Tositumomab + I-131 Brentuximab Vedotin Gemtuzumab ozogamycin Alemtuzumab Bevacizumab, Ziv-aflibercept, Ramucirumab Tyrosine kinase inhibitor Gefitinib, Erlotinib, Lapatinib, Neratinib Imatinib Dasatinib, Nilotinib, Sunitinib, Sorafenib, Pazopanib, Regorafenib
38 Cetuximab (Erbitux ) Chimeric monoclonal antibody to EGFR EGFR(Epidermal Growth Factor Receptor) = HER 1, c-erbb-1 치료예측인자 = K-ras Ras gene ; wild type, Rash 적응증 Metastatic colorectal cancer (K-/N-Ras wild type) 부작용 Infusion-related reaction (20% 정도 ) hypersensitivity, skin rash, nausea, weakness
39 Trastuzumab(Herceptin ) Humanized monoclonal antibody to HER-2 HER-2 Human Epidermal growth factor Receptor-2 = HER2/neu, c-erbb-2 모든정상유방상피세포에서도 HER-2 발현하며정상 level 에서는유방의성장과발달을조절하는역할을함유방암환자의 20 30% 가 HER-2 과발현 HER2 과발현인유방암은특히더 aggressive 함 적응증 : HER-2 가과발현된유방암 (06 ), 위암 (10 FDA approval) 부작용 Infusion related reaction, Cardiac failure/dysfunction
40 Anti-VEGFs Bevacizumab (Avastin*) monoclonal antibody directed against vascular endothelial growth factor (VEGF) Ziv-aflibercept (Zaltrap*) Recombinant fusion protein; soluble receptor that binds to human VEGF-A, VEGF-B and P1GF Aflibercept VEGFR-1 IgG VEGFR-2 Fc
41 Bevacizumab (Avastin ) Humanized monoclonal antibody to VEGF VEGF(Vascular endothelial growth factor) 신생혈관형성촉진인자 VEGF-A 와결합 수용체에결합하지못하도록하여하여신생혈관형성 (angiogenesis) 을억제하여암의성장을막음 적응증 : metastatic colorectal cancer, breast ca., NSCLC 부작용 Hypertension, thromboembolism, abdominal pain, GI bleeding (GI perforation), weakness
42 Ramucirumab (Cyramza ) VEGF receptor-2 antagonist (human monoclonal antibody) VEGF receptor-2 를특이적으로결합해 VEGF receptor 인 VEGF-A, VEGF-C, VEGF-D 의결합을차단 적응증 : Gastric cancer(advanced or metastatic), Colorectal cancer(metastatic), Non-small cell lung cancer(metastatic) 부작용 Hypertension, Diarrhea, Decreased RBC (requiring transfusion; 11%), Headache, Proteinuria, Hyponatremia, Epistaxis, Skin rash, neutropenia, anemia, hemorrhage, Infusion related reaction ( 16%), Arterial thrombosis..
43 Rituximab (Mabthera ) Chimeric anti-cd20 IgG1 monoclonal antibody Killer leukocyte CD20 Malignant B cell Complement 적응증 Rituximab Rituximab Relapsed or refractory low-grade or follicular CD 20(+), B-cell NHL Diffuse large B-cell CD 20(+) NHL in combination with chemotx 부작용 Infusion related reaction, headache, asthenia
44 Brentuximab (Adcetris ) Chimeric monoclonal antibody to CD30 ADC (Ab-Drug Conjugate) 적응증 Hodgkins disease 부작용 Neutropenia, peripheral neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, vomiting
45 Trastuzumab emtansine (T-DM1) Herceptin + DM1 (microtubule inhibitor) ADC (Ab-Drug Conjugate) 적응증 HER2-positive, unresectable locally advanced or metastatic breast cancer 부작용 Nausea, Pain that affects the bones, muscles, ligaments, and tendons, Bleeding, Thrombocytopenia, Headache, Liver problems, Constipation, Nosebleeds Step 1 Step 2 Step 3 Step 4 Step 1: Kadcyla* attaches to a HER2 receptor Step 2: Kadcyla* goes inside the cell Step 3: Breaks apart inside the cell Step 4: Works to help kill the cell
46 Radioimmunotherapy MOA Ibritumomab (Zevalin ) Tositumumab (Bexxar ) Anti-CD 20 antibody linked to radioactive indium(in-111) and yttrium(y-90) Indication Relapsed or refractory CD20+ follicular NHL Side effect Infusion related reaction, thrombocytopenia, neutopenia, nausea, vomiting, weakness Anti-CD 20 antibody linked to radioactive Iodine (I 131) Infusion related reaction, thrombocytopenia, neutopenia, nausea, vomiting, anorexia, weakness, hypothyroidism
47 Molecular targeted therapy (2) Small molecules Tyrosine kinase inhibitors (TK inhibitors, TKI) 특징 Molecular target : 선택적, 부작용적음 경구섭취 : 복용간편 면역반응을유발하지않아장기투여로인한부작용적음 종류 Target HER Drugs Gefitinib(Iressa ), Erlotinib(Tarcevar ), Lapatinib, Neratinib Bcr-abl Imatinib(Gleevec ) Multi- Dasatinib, Nilotinib, Sunitinib, Sorafenib(Nexavar ) Pazopanib(Votrient ), Regorafenib (Stivagar ) ALK* Crizotinib (Xalcori ), Ceritinib (Zykadia ) * ALK: Anaplastic Lymphoma Kinase
48 Gefitinib (Iressa ), Erlotinib (Tarceva ) EGFR targeted- tyrosine kinase inhibitor 적응증 : NSCLC 부작용 Ligand EGF-Receptor (EGFR) Membrane EGFR-tyrosine Kinase (EGFR-TK) Acne-form rash, dry skin, diarrhea, Interstitial lung disease Proliferation Tissue invasion Angiogenesis Inhibition of apoptosis Disemination Metastasis
49 Crizotinib (XALKORI ) MOA EML4-ALK gene translocation ALK fusion protein cancer ALK inhibitor 적응증 ALK-positive metastatic NSCLC (FDA appraoval 2011) NSCLC 2~7% 부작용 vision disorder, N/V/D, edema, constipation
50 Ceritinib (Zykadia ) MOA EML4-ALK gene translocation ALK fusion protein cancer ALK inhibitor 적응증 ALK+ advanced NSCLC previously treated with crizotinib 부작용 Diarrhea, Hemoglobin decreased, Increase in liver enzymes, Nausea, Vomiting, Increase in creatinine, Abdominal pain
51 Dasatinib (Sprycel ) 작용기전 Potent multi-targeted tyrosine kinase inhibitor BCR-ABL, SRC family, c-kit, PDGFR- β Similar imatinib, but bind to both active and inactive conformation of BCR-ABL kinase domain 적응증 Ph+ CML in chronic, accelerated, blast phase with resistance or intolerance to prior therapy (imatinib) Ph+ ALL with resistance or intolerance to prior therapy (imatinib) 부작용 myelosuppression, diarrhea, fatigue, fluid retention
52 Imatinib (Glivec ) 작용기전 BCR-ABL tyrosine kinase 저해 BCR-ABL tyrosine kinase: CML 에서 Philadelphia chr translocation 에의해형성 c-kit, platelet-derived growth factor 저해 적응증 Ph+ CML in chronic, accelerated, blast phase Kit+ unresectable or metastatic GIST 부작용 myelosuppression, N/V, fluid retention, LFT 상승
53 Lapatinib (Tykerb ) 선택적으로 ErbB1 (EGFR) 과 ErbB2 (HER2) 를동시에억제 적응증 : Metastatic breast cancer capecitabine 또는 aromatase inhibitor 와병용 부작용 EGFR Diarrhea, Acne-form rash, hand foot syndrome Lapatinib (Tykerb ) Her2 neu
54 Nilotinib (Tasigna ) 작용기전 2 nd BCR-ABL inhibitor 적응증 이매티닙치료에저항성또는 불내성을보이는만성기또는가속기의필라델피아염색체양성만성골수성백혈병성인환자의치료 부작용 Myelosuppression, QT prolongation, serum lipase, hepatotoxicity ( bilirubin, AST/ALT, ALP), e abnormalities
55 Olaparib (Lynparza ) PARP inhibitor Inhibition of PARP-1~-3 적응증 Treatment (monotherapy) of BRCA mutated (as detected by an approved test) advanced ovarian cancer in patients who have been treated with 3 or more prior lines of chemotherapy 부작용 Peripheral edema, Myelosuppression, hypertension, fatigue, N/V/D PARP: Poly ADP-Ribose Polymerase
56 Olmutinib (Olita ) 작용기전 비가역적인변이형 EGFR 선택적억제제 (EGFR-MUTANT selective inhibitor) 로써, 정상형 EGFR 보다변이형 EGFR 에서보다강력한효소억제활성을나타냄 적응증 이전에 EGFR-TKI 로치료받은적이있는 T790M 변이양성국소진행성또는전이성비소세포폐암환자의치료 부작용 설사, 오심, 발진, 가려움증, 식욕저하, 피부건조, 손 - 발바닥홍반성감각이상증후군
57 Radotinib (Supect ) 작용기전 BCR-ABL tyrosine kinase inhibitor 적응증 필라델피아염색체양성만성골수성백혈병 (Ph+CML) 성인환자의치료 부작용 Bone marrow suppression: Thrombocytopenia, neutropenia, anemia, febrile neutropenia, pancytopenia Hepatotoxicity: hyperbilirubineia, ALT N/V, Headache, Musculoskeletal pain, Hyperglycemia, serum lipase, skin rash
58 Regorafenib (Stivarga ) Multi-targeted tyrosine kinase inhibitor Kit, PDGFR : Inhibition of proliferation, PDGFR-ᵝ,FGFR : inhibition of tumor microenvironement signaling, VEGFR-1~-3, Tie2 : inhibitions of angiogenesis 적응증 Gastrointestinal stromal tumors(imatinib, sunitinib 후재발 ) Metastatic colorectal cancer(anti-vegf therapy, or anti-egfr therapy (if KRAS wild type) 후재발 ) 부작용 Hypertension, Palmar-plantar erythrodysesthesia, lymphopenia, Proteinuria, N/VD
59 Pazopanib (Votrient ) Multi-targeted tyrosine kinase inhibitor 200mg, 400mg inhibits tumor growth via angiogenesis by inhibiting cell surface vascular endothelial growth factor receptors 적응증 advanced renal cell cancer (RCC) FDA approval advanced thyroid cancer, refractory metastatic soft tissue sarcomas Unlabeled use 부작용 Myelosuppression, hypertension, fatigue, N/V/D
60 Sorafenib (Nexavar ) Multi-targeted TK inhibitor Inhibition of Raf kinases (CRAF, BRAF, and mutant BRAF) Inhibition of cell surface kinase receptors (VEGFR-2, VEGFR-3, PDGFR-beta, ckit, and FLT-3) 적응증 advanced renal cell carcinorma hepatocelluar carcinoma 부작용 Hand-foot syndrome, hypertension, diarrhea, rash
61 Sunitinib (Sutene ) Multi-targeted tyrosine kinase inhibitor Platelet-derived growth factor receptor, vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), FMS-like tyrosine kinase-3 (FLT3), c-kit 적응증 GIST (Imatinib 요법에실패한경우 ) advanced renal cell carcinorma 부작용 Diarrhea, fatigue, fever, nausea, skin discolorization, hypertension, hand-foot syndrome, bleeding
62 문제 3. HER2-targeted drugs
63 4. Immune therapy & Others
64 Anti-cancer immunotherapy
65 Immune checkpoint 암세포는 T 세포의면역기능을억제하는리간드를과도하게발현하며, 이러한 T 세포를억제하는과정 PD-1/PD-L1 CTLA-4
66 CTLA-4 and PD-1 Pathways
67
68 Bortezomib (Velcade ) 작용기전 Proteasome inhibitor * Proteasome: Enzyme complex Velcade Responsible for degradation and activation of altered and regulatory proteins Cell Cycle Angiogenesis 적응증 Multiple myeloma 26S proteasome Apoptosis Myeloma cell interaction with microenvironment 부작용 Thrombocytopenia, neutropenia, N/V, peripheral neuropathy, fatigue
69 Thalidomide
70 Thalidomide 적응증 Newly-diagnosed Multiple myeloma 부작용 Drowsiness, somnolence, peripheral neuropathy, edema, skin rash, neutropenia, thromboembolic event 주의 최기형성에대한주의 : 피임필수 가임기 (4 주 ), 비가임기및남성 (8 주 ) 처방가능 최기형성에대한철저한관리를위해탈리도마이드위해관리프로그램 (TRMP) 에등록된의사, 약사만이처방및조제
71 Lenalidomide (Revlimid ) 적응증 Mantle cell lymphoma, Multiple myeloma, Del 5q Myelodysplastic Syndromes (MDS) 부작용 thrombocytopenia, neutropenia, drowsiness, edema, N/V/D/C peripheral neuropathy, skin rash 주의 CLcr<30ml/min 투석환자 30 CLcr <50ml/min CLcr <30ml/min 비투석환자 (48 시간마다 ) 최기형성에대한주의 : 피임필수 가임기 (4 주 ), 비가임기및남성 (8 주 ) 처방가능 최기형성에대한철저한관리를위해레날도마이드위해관리프로그램 (REMS) 에등록된의사, 약사만이처방및조제
72 mtor inhibitor 작용기전 targeted inhibitors of mtor (mammalian target of rapamycin) kinase activity Cell proliferation Angiogenesis Cell metabolism
73 mtor inhibitor 약제 Temsirolimus (Torisel ) Everolimus (Afinitor ) 적응증 Advanced renal cell carcinoma 부작용 Rash, stomatitis, edema, anemia, hypertension, abn. hepatic func. hyperlipidemia
74 문제 4. 다음항암제중 in-line-filter 를사용하여투약하지않아도되는약제는? A. Paclitaxel B. Cabazitaxel C. Nivolumab D. Temsirolimus E. Trastuzumab (IV) E. Trastuzumab (IV) F. Trastuzumab emtansine (T-DM1)
75 Anticancer drugs-filter set 항암제 Blinatumumab Cabazitaxel Nivolumab Paclitaxel Pembrolizumab 구분 무균, 비발열성, 저단백질결합인라인필터 (0.2 마이크론 ) ( 탁솔필터안됨 - 암젠 ) 탁솔필터 무균, 비발열성, 저단백질결합인라인필터 (0.2~1.2) ( 탁솔필터안됨-오노제약 ) ( 허가가항변경 ) 0.22-micron in-line filter and polyethylene-lined (non-pvc) administration set 한국엠에스디제공 : 0.2 to 5 micron sterile, nonpyrogenic, low-protein binding inline or add-on filter Ramucirumab 탁솔필터 ( 필수아니고권장사항 - 한국릴리 ) Temsirolimus Thiotepa 화이자제공 : polyethylene-lined non-dehp administration tubing and a polyethersulfone end filter (0.2 to 5 micron) 탁솔필터 Trastuzumab emtansine 탁솔필터
76 경청해주셔서감사합니다. euri@ncc.re.kr
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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
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Introduction to Medical Oncology and Molecularly Targeted Therapy 서울대학교의과대학내과학교실분당서울대학교병원혈액종양내과 김유정 연도별성별암발생자수추이 70 분당서울대학교병원 제 8 회분당서울대학교병원내과연수강좌 2012 평균수명까지생존시암발생확률, 2009 주요암종발생분율, 2009 분당서울대학교병원 71
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2008.8.31. 내과연수강좌 표적치료제의 허와실 - 항암치료의최신동향- 분당서울대학교병원혈액종양내과이근욱 Treatment of Cancer 1890-1980s 1990s 2000s Surgery Radiotherapy Chemotherapy Biologic therapy Gene therapy? Target-based Therapy Most Anticancer
Introduction 한국인에서암은지난 10 년간사망원인 1 위였으며, 암발생은지속적으로증가추세에있다. 최근암조기발견과암치료의발전으로암생존율이향상됨에따라생존기간뿐아니라암치료에의한장기적영향과생존자의삶의질에대한관심이높아지고있다. 한국인의주요암의 5 년상대생존율 : 46.
항암치료의이해 순천향대학교병원 종양혈액내과박희숙 Introduction 한국인에서암은지난 10 년간사망원인 1 위였으며, 암발생은지속적으로증가추세에있다. 최근암조기발견과암치료의발전으로암생존율이향상됨에따라생존기간뿐아니라암치료에의한장기적영향과생존자의삶의질에대한관심이높아지고있다. 한국인의주요암의 5 년상대생존율 : 46.3% (2002 년 ) 2 우리나라암발생률,
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한약치료와표적항암요법 ( 아피니토 ) 을병행하여부분관해된신세포암간전이환자 1 례 Abstract Sung-Hwan Chang 1, Ji-Hye Park 1,2, Hwa Seung Yoo,2*
https://doi.org/10.15432/jkto.2017.22.2.013 한약치료와표적항암요법 ( 아피니토 ) 을병행하여부분관해된신세포암간전이환자 1 례 Abstract Sung-Hwan Chang 1, Ji-Hye Park 1,2, Hwa Seung Yoo,2* 1 JangDeuk Integrative Medical Center, Korean Medicine
Δ Epidermal growth factor receptor (EGFR) is well established target for cancer treatment and EGFR tyrosine kinase (TK) inhibitors such as gefinitib and elotinib have been developed as anti-cancer drugs.
2016 학년도약학대학면접문제해설 문제 2 아래의질문에 3-4분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세
본문제에대한지적소유권은동국대학교에있습니다. 본교의서면허락없이무단으로출판, 게재, 사용할수없습니다. 문제 2 2016 학년도약학대학면접문제 아래의질문에 3-4 분이내로답하시오. 표피성장인자수용체 (epidermal growth factor receptor, EGFR) 는수용체티로신 인산화효소군 (receptor tyrosine kinases, RTKs) 의일종으로서세포의생존과증식
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Apr. 30. 2016. GBCC in JeJu Island Sensitization of breast cancer cells to chemotherapeutic drugs by metabolic regulation InChul Park, Ph. D. Korea Institute of Radiological & Medical Sciences (KIRAMS)
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항암치료의원칙및 심사기준 순천향대학교병원 종양혈액내과박희숙
항암치료의원칙및 심사기준 순천향대학교병원 종양혈액내과박희숙 암치료의목표 일차목표 : to eradicate the cancer( 암제거 ) 일차목표가불가능한경우 (Palliation, 완화요법 ) 진행방지 ( SD PR CR) 증상의완화생명연장삶의질개선 ( 통증완화등 ) 항암치료 수술 방사선치료 항암화학요법 세포독성치료 면역요법 생물학적치료 유전자요법 대체요법
권두칼럼 조찬휘 대한약사회장 회원의 손톱 밑 가시 뽑는 소통, 국민에게 신뢰 주는 커뮤니케이션 대한약사회장 조 찬 휘 커뮤니케이션의 어원적 정의는 공유, 공통, 나누어갖다 등으로 되어 있습니다. 커뮤니케이션은 언어나 몸짓, 화상 등의 물질적 기호를 매개수단으로 하는 정
CONTENTS 권두칼럼 발언대 인터뷰 업체탐방 캠페인 02 04 06 10 14 회원의 손톱 밑 가시 뽑는 소통, 국민에게 신뢰 주는 커뮤니케이션 조찬휘 대한약사회장 약사 직역 향상은 약계 상생 및 생존 전략에 달려있다 손의동 대한약학회장 의약분업 시행 초기 미비된 환경 정비하고 약국경영 안정화에 최선을 다했다 한석원 전 대한약사회장 R&D 중심기업 한미약품을
항암치료란.ppt [호환 모드]
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암! 알아야이겨낼수있죠! - 항암치료란? - 한림대학교성심병원 혈액종양내과 암? 도대체왜? 암의두가지큰특징 1) 정상적인범위를벗어나끊임없이세포분열을하고성장 - 양성및악성종양 2) 다른세포가차지하고있는고유영역을침범함 - 악성종양 대부분의암은한개의비정상세포로부터 알수가없어요? 암전이의단계 조기발견할경우암의 5년생존율 유방암 : 95% (0 기암 : 100%)
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제 7 회페루자국제암회의 항구토요법지침 (2008 년 3 월최신개정 ) BASED ON: THE CONSENSUS CONFERENCE ON ANTIEMETIC THERAPY* 한국호스피스완화의료학회 * Conference conducted in March 2004 MASCC (Multinational Association of Supportive Care in
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대한내과학회지 : 제 82 권제 5 호 2012 http://dx.doi.org/10.3904/kjm.2012.82.5.532 특집 (Special Review) - 구역과구토 (nausea and vomiting) 항암치료중구역과구토의처치 건양대학교의과대학내과학교실 송경호 Management of Chemotherapy Induced Nausea and Vomiting
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암세포의위험한여행 한국과학기술원 김미영 강의개요 전이란무엇인가? 전이는어떤과정을통해진행될까? 전이예측방법은어떤것들이있을까? Cancer ( 악성종양 ) US South Korea 질병사망률질병사망률 1. 심장병 26% 1. Cancer 26.7% 2. Cancer 23% 2. 뇌출혈 12.7% 3. 뇌출혈 5.6% 3. 심장병 7.9% >20,000 환자가악성종양에의해매일사망함
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References : 1. ATAC Completed Treatment Analysis: Anastrozole demonstrates superior efficacy and tolerability compared with tamoxifen. Howell A on behalf of the ATAC Trialists Group San Antonio 2004.
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대한내과학회지: 제 80 권 제 6 호 0 진행성 위암에 대한 차 요법으로 Docetaxel, Cisplatin, 5-FU 복합화학요법의 효과와 안전성 고신대학교 의과대학 내과학교실 김부경 박무인 박선자 김규종 문 원 정수현 김혜수 남성진 Docetaxel, Cisplatin, 5-FU Combination Chemotherapy as a First-Line
항암치료와탈모 저자최선서울성모병원약제부입원조제 UM 약학정보원학술자문위원 개요 항암치료를받는환자들에게흔히나타나는부작용중하나가탈모이다. 탈모는치명적인부작용은아니지만외모에대한영향으로인해치료를거부하는주요원인중하나로작용하곤한다. 이에탈모를유발하는주요항암제에대한정보를알아보고,
항암치료와탈모 저자최선서울성모병원약제부입원조제 UM 약학정보원학술자문위원 개요 항암치료를받는환자들에게흔히나타나는부작용중하나가탈모이다. 탈모는치명적인부작용은아니지만외모에대한영향으로인해치료를거부하는주요원인중하나로작용하곤한다. 이에탈모를유발하는주요항암제에대한정보를알아보고, 항암치료에따른탈모의예방이나관리방법에대해알아보고자한다. 키워드 항암치료, 탈모 1. 항암치료유발탈모의개요
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혈액종양내과분과연수강좌 2011 Advances in treatment strategies Breast Cancer 연세의대내과학교실 손주혁 Molecular Classification of Breast Cancer Issues Adjuvant taxanes Avoiding adjuvant chemotherapy Anthracyclines in EBC Adjuvant
표적치료제의모든것소분자키나제억제제 (1) 저자최병철 약학정보원학술자문위원 머리말 소분자키나제억제제 (small molecule kinase inhibitor) 는신호전달경로 (signal transduction pathway) 를표적으로하므로넓은의미로는신호전달경로억제제
표적치료제의모든것소분자키나제억제제 (1) 저자최병철 약학정보원학술자문위원 머리말 소분자키나제억제제 (small molecule kinase inhibitor) 는신호전달경로 (signal transduction pathway) 를표적으로하므로넓은의미로는신호전달경로억제제라고한다. 소분자키나제억제제는모두경구제로서, 2001년최초로승인된 BCR-Abl 티로신키나제억제제
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Systemic Treatment of Pancreatic Neuroendocrine Tumors 장흥문 울산대학교의과대학서울아산병원종양내과학교실 췌장에생기는신경내분비종양 (pancreatic neuroendocrine tumor: PNET) 은매우드문종양으로주로췌장의 islets of Langerhans 에서발생하므로 islet cell tumor라고도부른다.
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