항암제분류

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항암제의분류와약리작용 2016. 9. 12 국립암센터약제부 전혜원

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

1. Cytotoxic antineoplastics

Cell cycle 과항암제의작용

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 Cytotoxic effect Inhibition of DNA replication and transcription Mispairing of DNA Strand breakage Toxicity Myelosuppression Infertility Secondary malignancy

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 )

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

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)

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 )

2) Topoisomerase inhibitors Topoisomerase Regulation of DNA supercoiling Topoisomerase inhibitors 종류 Topoisomerase I inhibitor : Irinotecan, topotecan Topoisomerase II inhibitor : Anthracyclines, Epiphodophyllotoxins

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

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

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

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

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

Antimetabolite Pemetrexed (Alimta ) Mutitargeted antifolate TS, DHFR, GARFT Co-medication 부작용을줄이기위해투여 (rash, myelosuppression) Folate 350-1000mcg/day pemetrexed 투여 1 주일전부터투여종료 3 주후까지 Vit B12 1000mcg pemetrexed 투여 1 주일전부터 9 주간격으로 IM Dexamethasone 4mg bid, pemetrexed 투여전날, 투여당일, 투여다음날

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

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

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

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

문제 1. 다음중골수억제부작용이제일심각한약제는? A. Irinotecan B. Carboplatin C. Docetaxel D. Busulfan : alkylating agent, BMT

2. Hormonal agents

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

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

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

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 *)

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 - 10.8mg/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

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

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

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.

약제부고위험약물

약제부고위험약물

3. Molecular targeted therapy

Molecular targeted therapy R R Antibody-Based Membrane K K ATP Small Molecule Inhibitor Lung Prostate Breast Ovary Gastric Colon

Molecular targeted therapy (1) Mechanism of Action: 단클론항체 A~D 기전 A. 세포사멸 B. ADCC(Antibodydependent cellmediated cytotoxicity) C. 보체연쇄반응 D. 신생혈관생성억제

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

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

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

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

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

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..

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

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

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

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

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

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

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

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

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

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

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

Nilotinib (Tasigna ) 작용기전 2 nd BCR-ABL inhibitor 적응증 이매티닙치료에저항성또는 불내성을보이는만성기또는가속기의필라델피아염색체양성만성골수성백혈병성인환자의치료 부작용 Myelosuppression, QT prolongation, serum lipase, hepatotoxicity ( bilirubin, AST/ALT, ALP), e abnormalities

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

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

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

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

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

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

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

문제 3. HER2-targeted drugs

4. Immune therapy & Others

Anti-cancer immunotherapy

Immune checkpoint 암세포는 T 세포의면역기능을억제하는리간드를과도하게발현하며, 이러한 T 세포를억제하는과정 PD-1/PD-L1 CTLA-4

CTLA-4 and PD-1 Pathways

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

Thalidomide

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

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

mtor inhibitor 작용기전 targeted inhibitors of mtor (mammalian target of rapamycin) kinase activity Cell proliferation Angiogenesis Cell metabolism

mtor inhibitor 약제 Temsirolimus (Torisel ) Everolimus (Afinitor ) 적응증 Advanced renal cell carcinoma 부작용 Rash, stomatitis, edema, anemia, hypertension, abn. hepatic func. hyperlipidemia

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)

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 2016.4.1) 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

경청해주셔서감사합니다. e-mail : euri@ncc.re.kr