강동경희대학교병원 약품정보지 - khnmc.or.kr

1 VOL .12 10 , , , , , 134-090 892 [TEL] / ( ) [FAX] / Torisel inj. ( ) mTOR kinase inhibitor (Renal Cell Carcinoma, RCC) ( , : HH919) Torisel inj. ( ) 1. 2. Temsirolimus 30mg/3mL 3. - ( ) / / ( ) 4. mTOR(mammalian Target of Rapymycin) kinase inhibitor , mRNA G1 S p70S6K 4E-BP1 5.

2 6. 1 25mg 30~60 IV Infusion : 30 diphenhydramine 25-50mg( ) IV : ANC<1,000/ , PLT<75,000/ NCI CTCAE grade 3 7. Peak : : ( Sirolimus: 588L) : ( Sirolimus: ) : CYP3A4 : feces(94%), urine( ) 8. : (37%), (19%), (21%), (27%), (20%) : (2%) : (20%), (18%) : (28%), (12%), (26%) : (21%), (26-89%), (27- 83%), (32%) : (47%), (19%), (10%), (14%), (11%) 9. Temsirolimus 1 2017 10 10.

3 CYP3A4 / : Temsirolimus Cmax AUC , sirolimus Cmax AUC CYP3A4 / . 11. : FDA D( ) : , sirolimus rat . , . 12. , (2~8 C) ( ) .. , . / , 3 ..( ) Reference 1. : 2. Lexicomp online: 3. : ( ) 2 2017 10 (Renal Cell Carcinoma, RCC) Special Issue Localized Regional Distant Unknown 1.

4 2014 , 2014 ( 4,471 / 217,057 ). , 80~85% Renal Cell Carcinoma . (stage) (dissemination) , , . [Table 1] 5 (2010-2014*) * (2014 ) : , [ 1] . High-dose Interlukin-2, Interferon- , sorafenib, sunitinib target 20% , 2015 nivolumab.

5 [ 1] NCCN 2018 Kidney cancer 2. Target Therapy 1) Temsirolimus ( ) : mTOR(mammalian target of rapamycin) kinase inhibitor , - 1 25mg 30-60 - 30 diphenhydramine 25-50mg - ANC< 1,000/mm3, PLT<75,000 /mm3 NCI CTCAE Gr3 5mg - T. Bilirubin > AST > 15mg - T. Bilirubin > : (47%), (51%), (41%), (37%), (35%), (32%), (89%), (87%), (83%), (94%), (53%), (40%), (24%), serum creatinine (57%) 2) Axitinib ( 1mg, 5mg) : 2 tyrosine kinase inhibitor vascular endothelial growth factor receptors(VEGFR-1, VEGFR-2, VEGFR-3) , - 5mg BID - (Child-Pugh classes B): BID - 2 Gr 2 , 7-10mg BID - Gr 3.

6 5mg BID 3mg BID 2mg BID 3 2017 10 [ 2] 4 3) Dark age (2005 ): High-dose Interlukin-2, Interferon- , ~15 Modern age(2005-2014): 7 , ~30 Golden age(2015-2025): 3 Diamond age(2025~) [ 3] 4) : (55%), (40%), (39%), (39%), (34%), (32%), (31%), (27%), (21%), (13%), (39%), (28%), (25%), (19%), (17%), serum creatinine (55%), (33%) 3) Cabozantinib ( 20mg, 40mg, 60mg) : proinvasive receptor tyrosine kinases (RTKs) , , , - 60mg QD.

7 - Gr2 Gr3 Gr1 20mg - (Child-Pugh classes A and B): 40mg QD - : , , ( , ), , , , : (63-74%), (46%), (42-50%), (34%), (33-61%), (41-56%), (20%), (11-18%), (17%), (11-19%), (16%), (21%), (53%), (35%), (35%), ALT (68-86%), AST (74-86%) 4) Lenvatinib ( 4mg. 10mg) : VEGFR1 (FLT1), VEGFR2 (KDR), VEGFR3 (FLT4), FGFR1-4, PDGFR , KIT RET RTK(receptor tyrosine kinase) , - Lenvatinib 18 mg 1 1 ( everolimus 5 mg 1 1 ) - : , (12%), (38%), (15%), , (35%), (73%), (31%), (67%), (54%), , (67%), (47%), (34%), (32%), (12%), (21%), / ( 62%), (21%) : 12.

8 1 3. immunotherapy 1) Nivolumab ( 20mg, 100mg) : G4 (IgG4) PD-L1 T-Cell PD-1 T-Cell . , : 3mg/kg, 2 60 IV : (34%), (56%), (27%), (28%), (25%), (23%), (23%), (28%), (21%), (20%) 4 2017 10 Reference 1) Kidney Cancer Ver 1. 2018 NCCN guidelines 2) .. 2016 3) Renal cell carcinoma. Nat Rev Dis Mar 9;3:17009. 4) Systemic Therapy for Metastatic Renal-Cell Carcinoma. N Engl J Med 2017;376:354-366 5) Lexicomp online: 6).

9 ( ) [ ] (Renal Cell Carcinoma) 5 2017 10 Sunitinib Pazopanib Sorafenib Axitinib Temsirolimus Everolimus Lenvatinib Cabozantinib Nivolumab TKI TKI TKI TKI, VEGFR-1,2,3 inhibitor m-TOR inhibitor m-TOR inhibitor TKI TKI PD-1 inhibitor PO PO PO PO IV PO PO PO IV FDA * GIST, RCC, pNET RCC, soft tissue sarcoma HCC, RCC, DTC RCC RCC MBC, SRGA, RCC, GI/Lung/pNET RCC, DTC RCC, Thyroid cancer , HCC, SCLC, DTC RCC , NSCLC, RCC, cHL, , NCCN (Category 1) 1ST line - Category 1 (preferred) 1ST line 2nd line Category 1 1ST line Category 1 Lenvatinib + Everolimus : 2nd line Category 1 2nd line - Category 1 (preferred) P( , Palliative) S( , salvage) RCC , (P, S 1 ) RCC (P, S 1 ) Sunitinib, Pazopanib, Sorafenib , RCC (S 2 ) RCC , 50mg QD*4 +2 800mg QD 400mg BID 5mg BID 1 25mg 30-60 10mg QD/ 5mg QD 60mg QD 3mg/kg *2 60 ULN: Gr: NCI-CTCAE v4 - Gr2:200mg - - Child-pugh B: BID - T.

10 Bil 1~ or AST>ULN: 15mg/week - T. Bil> : - Child-pugh A: QD - Child-pugh B: 5mg QD , : 40mg QD Gr2: Gr3: - - - - - - , : Creatinine>6 *ULN: * DTC : Differentiated thyroid carcinoma, HCC : Hepatocellular carcinoma, RCC : Renal cell carcinoma, MBC : meta Breast Cancer, pNET : , cHL : HL, SEGA: : 3 LDH Hemoglobin Corrected serum calcium level > 10mg/dl ( mmol/L) 1 Karnofsky performance score 70 NCI-CTCAE v4.