Anthracycline 類化療藥物引起的心臟毒性概論

1 101 98 10 1 Anthracycline Anthracyclines Anthracyclines DNA DNA Polymerases DNA RNA Anthracyclines Anthracyclines Doxorubicin Fe-dependent Fe-independent Doxorubicin (Oxidative stress) ROS(Reactive oxygen species) 1. [6] Doxorubicin 400 550 700 mg/m2 3% 7% 18% [3] Doxorubicin 550 600 600 mg/m2 4% 18% 36% Doxorubicin 550 mg/m2 Epirubicin 900 mg/m2[4] Anthracyclines Anthracyclines Anthracyclines 2.

2 IV bolus IV bolus 3. 101 98 10 2 Anthracycline Anthracycline 4. Mediastinal irradiation Anthracycline Anthracyclines 5. Anthracyclines Cyclophosphamide Paclitaxel Docetaxel Trastuzumab 6. Cyclophosphamide Mediastinal irradiation Anthracyclines Anthracyclines 1.

3 Doxorubicin Doxorubicin Epirubicin Idarubicin Mitoxantrone Epirubicin mg Doxorubicin Epirubicin 900 mg/m2 Epirubicin Doxorubicin Epirubicin Idarubicin Anthracyclines (Congestive heart failure CHF) Doxorubicin > Epirubicin> Idarubicin Idarubicin 150mg/m2[4] Mitoxantrone Anthraquinone Anthracyclines Mitoxantrone 140 mg/m2[4] Doxorubicin (Liposome) Doxorubicin 500 mg/m2 101 98 10 3 Doxorubicin Doxorubicin 2.

4 DexrazoxaneDexrazoxane Anthracycline Dexrazoxane EDTA Anthracyclines Dexrazoxane Anthracyclines Dexrazoxane Doxorubicin 300 mg/m2 Dexrazoxane Dexrazoxane Doxorubicin 10 1 50 mg/m2 Doxorubicin 500 mg/m2 Dexrazoxane Dexrazoxane Doxorubicin Dexrazoxane 30 ( 40 ml/min) Dexrazoxane Doxorubicin 5 1 Doxorubicin Dexrazoxane Doxorubicin 10 1 ASCO Dexrazoxane Doxorubicin Doxorubicin 300mg/m2 Dexrazoxane Doxorubicin 300mg/m2 Dexrazoxane Anthracyclines Anthracyclines (Afterload) (Angiotensin converting enzyme inhibitor ACEI ) (Diogxin ) Carvedilol(Beta blocker) Anthracyclines LVEF(Left ventricularejection fraction)

5 Doxorubicin 100 mg/m2 Doxorubicin 101 98 10 4 (Radionuclide Angiocardiography) LVEF LVEF 1. Baseline LVEF ( 50%) 250~300 mg/m2 400 mg/m2 EKG Cyclophosphamide 450 mg/m2 2. Baseline LVEF ( 50%) LVEF 30% Doxorubicin LVEF 30%~50% LVEF 10% 30% Doxorubicin 1991 Doxorubicin Anthracyclines Dexrazoxane Anthracyclines ASCO Dexrazoxane ACEI Anthracyclines -Dexrazoxane- Anthracyclines Anthracyclines

6 Anthracyclines 101 98 10 5 1 Cardiotoxicity of chemotherapeutic agents. Vinita B. Pai and Milap C. safety 2000 Apr; 22(4):263-3022 Cardiotoxicity of cancer therapy. Justin D. Floyd, Duc T. Nguyen, Raymond , Qaiser Bashir, Donald C. Doll, and Michael C. Perry. Journal of clinicaloncology 23:7685-76963 Current Concepts: Doxorubicin-Induced , Pawan K.;Iliskovic, Engl J Med 1998 Sep 24;339(13):900-54 Epirubicin cardiotoxicity: an analysis of 469 patients with metastatic breastcancer. Ryberg M; Nielsen D; Skovsgaard T; Hansen J; Jensen BV;Dombernowsky P. J Clin Oncol 1998 Nov;16(11) Dexrazoxan. A review of its use for cardioprotection during anthracyclines che-motherapy.

7 Risto S. Cvetkovi and Lesley J. Scott. Drugs 2005; 65(7):1005-10246 Cardiotoxicity of Anthracycline -like chemotherapy agents. Justin Floyed, JamesP Morgan and Michael C Iron isnot involved in oxidative stress-mediated cytotoxicity of doxorubicin ,GJMdenHartog,Timnek,LSchr terov ,EKvasnikov and Journal of Pharmacology(2006) 149, 920 Different dosage schedules for reducing cardiotoxicity in cancer patientsreceiving Anthracycline Dalen EC; van der Pal HJ; Caron HN;Kremer LC. Cochrane Database Syst Rev. 2006 Oct 18;(4) Doxorubicin administration by continuous infusion is not cardioprotective: theDana-Farber 91-01 Acute Lymphoblastic Leukemia protocol.

8 Lipshultz SE;Giantris AL; Lipsitz SR; Kimball Dalton V; Asselin BL; Barr RD; Clavell LA;Hurwitz CA; Moghrabi A; Samson Y; Schorin MA; Gelber RD; Sallan SE; ColanSD. J Clin Oncol. 2002 Mar 15;20(6) Chronic progressive cardiac dysfunction years after doxorubicin therapy forchildhood acute lymphoblastic leukemia. Lipshultz SE; Lipsitz SR; Sallan SE;Dalton VM; Mone SM; Gelber RD; Colan SD. J Clin Oncol 2005 Apr20;23(12) Cardiac abnormalities 15 years and more after adriamycin therapy in 229childhood survivors of a solid tumour at the Institut Gustave Roussy. Pein F;Sakiroglu O; Dahan M; Lebidois J; Merlet P; Shamsaldin A; Villain E; deVathaire F; Sidi D; Hartmann O.

9 Br J Cancer2004 Jul 5;91(1) Noninvasive evaluation of late Anthracycline cardiac toxicity in childhood cancersurvivors. Hudson MM; Rai SN; Nunez C; Merchant TE; Marina NM; Zalamea N;Cox C; Phipps S; Pompeu R; Rosenthal D. J Clin Oncol. 2007 Aug20;25(24):3635-43.