1. www.OncologyEducation.ca Cardiotoxicity associated with the cancer therapeutic agent sunitinib Telli ML, Witteles RM, Fisher GA, Srinivas S. Reviewed by: Dr. Daniel Heng and Dr. Lori Wood Date posted: April 4, 2008

2. www.OncologyEducation.ca SYNOPSIS Sunitinib-related cardiotoxicity was not prominent in phase II and III trials of this drug in metastatic renal cell carcinoma: Phase II Motzer et al JAMA 2006: 1/106 MI Phase II Motzer et al JCO 2006: 2/63 grade 3/4 LVEF decline Phase III Motzer et al NEJM 2007: 2/375 grade 3/4 LVEF decline; but 21% experienced some sort of LVEF decline Because trial patients are well selected and few have existing heart disease, cardiotoxicity may not be highlighted in these trials. A retrospective chart review of all patients on sunitinib treated for metastatic RCC or GIST at the Stanford University Comprehensive Cancer Center was done in this study.

3. www.OncologyEducation.ca RESULTS 7/48 (15%) patients were found to have grade 3/4 symptomatic LV dysfunction. Occurred at 22-435 days after starting sunitinib. 3/5 patients with follow-up investigations show persistent LVEF dysfunction after stopping sunitinib and treatment with heart failure medications Risk factors for cardiac toxicity in these patients included: History of heart failure History of coronary artery disease Low body mass index Note: the patient population includes those with GIST and those previously treated with imantinib. Thus, the true effect of sunitinib in the first-line RCC population is less clear.

4. www.OncologyEducation.ca BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS The true incidence of cardiotoxicity may be higher in the general population treated with sunitinib compared to clinical trials populations. There are no practice guidelines for cardiac monitoring while on sunitinib and most Canadian oncologists do not routinely test for this in all patients. Patients with existing coronary artery disease, heart failure or symptoms of cardiac disease should have baseline cardiac investigations performed before sunitinib administration. Follow-up investigations should be performed at the discretion of the oncologist. Routine cardiac monitoring for all patients is not indicated at this time. Larger population studies are required in order to make more evidence-based recommendations. Aggressive management of hypertension should be undertaken in patients on sunitinib.