CLINICAL
NEWS
American College of Cardiology Extended Learning
ACCEL interviews and topical summaries of cardiology’s most interesting research areas
Cardiac Safety During Chemotherapy:
The Scope Of The Problem
T
he prognosis of patients with hematologic malignancies has improved in the last years due to the use of new chemotherapeutic and antineoplastic drugs as well as more dose-intensive regimens. However, it’s become better appreciated in the last few years that many cancer therapies confer an increased risk of adverse cardiac outcomes such as HF and cardiomyopathy (CM). For example, several widely used agents for the adjuvant therapy of breast cancer can cause abnormalities in LV function, leading to HF or CM that can persist many years after the conclusion of chemotherapy. While early investigation focused on the anthracyclines, long known for their cardiotoxic effects, newer agents, too, put patients at risk for myocardial injury. Because 40.8% of women diagnosed with breast cancer in the United States are at least 65 years of age and because risk for CV events increases with age, it is crucial to better To listen to an understand the risk of cardiointerview with toxicity associated with newer Daniel J. Lenihan, MD, about heart biologic agents used for treatsafety during ing older adults with cancer chemotherapy, visit youtube.cswnews. outside of clinical trials. org or scan the QR Recently, Chen et al. used code. The interview Medicare data to estimate was conducted by Peter A. HF and CM rates following McCullough, MD. chemotherapy and adjuvant trastuzumab in older women for breast cancer.1 In female Medicare beneficiaries with breast cancer, use of this HER2/neu-targeted therapy increased by more than 8-fold
from 2000 through 2007 among patients receiving any form of adjuvant therapy. That might make this group an important target for preventing and managing cancer therapy–induced cardiotoxicity. Almost 50,000 women aged 67–94 years with early-stage breast cancer were identified. Adjusted 3-year HF/CM incidence rates were higher for patients receiving trastuzumab (32 per 100 patients) and anthracycline plus trastuzumab (42 per 100 patients) compared with no adjuvant therapy (18 per 100 patients). In terms of adjusted risk, compared to patients who received no adjuvant chemotherapy or trastuzumab, use of trastuzumab was associated with a higher absolute adjusted incidence rate for HF or CM over 3 years (TABLE 1). Importantly, in this analysis, the cardiac complication rates after trastuzumab therapy for older women were higher than those reported from clinical trials. Other so-called “targeted” cancer drugs can increase the risk of fatal cardiac events, too. A recent meta-analysis led by scientists at DanaFarber Cancer Institute evaluated data from 4,679 patients participating in 10 randomized controlled trials.2 The study looked at three drugs: sorafenib, sunitinib, and pazopanib, which block the vascu ?"V?F?F?V??w&?wF?f7F?"?dTtb?G?&?6??R???6R&V6WF?'2??6?6W"6V??2?F?W6RvV?G2?fR&V6??RF?R6?&?W'7F??R?bF?W&?f?"?V?&W"?b6?6W'2???fW7F?vF?'2???VBF?R??6?FV?6R?b'FW&??F?&??&?F?2WfV?G2?&?VVF??r??b??B?F?W"WfV?G2?F?R??6?FV?6R?bfF?6???6F???2v2?RR??F?V?G2v??&V6V?fVB???bF?RF?&VRG'Vw2?6??&VBF??rR??6?FV?6R??F?V?G2v?fV?7F?F&BG&VF?V?G2?"?6V&?2??F?W"G?W2?bvV?G2???6?VF??rR?f?V?'W&6???B?F??dTtbF?W&????r?fR6???v?VFvVB5bVffV7G2?F???F?W2?v?WF?W"Wf?VF??r??FW ??W7F&?6?VBF?W&?W2?"?WvW"&????v?72?B6?6??VBF&vWFVBF?W&?W2?&WGG??V6????bF?V???r?fR&V6?v?VB6&F??F???2VffV7G2?t?B4?$RD??R$?UB?C??F?RF?v??r6&F?2VffV7G2?b??FW&?6?6W"F?W&????fW7BF?&?Vv?F?fW'6?G??b?V6???6?2??6?VF??rV?F?F?V??F???6?G??BF?&V7B??7?FR???W'???v??FV?6???6??fW'F??rV??R??&?F?'2?4R???fR&VV?FV???7G&FVBF?6??rF?R&?w&W76????b?b7?7F??2G?6gV?7F????BF?&WfV?B?b??7??F??F?2??v??&?6?F?V?G2?F?W6RG'Vw2?fR?6?&VV?6??v?F?FV7&V6R??'F?G????7B??f&7F???F?V?G2v?F??bG?6gV?7F????"?V'Bf??W&R???6?VF??r?F?&7?6??R??GV6VB4???6??4R?2?fR&WfV?F?fRVffV7G2v??7B6?V??F?W&???GV6VB6&F??F???6?G?????????FV?2?B??GV?G2v?F?V&?6&F??F???6?G??6???"&W7V?G2?fR&VV??'F??VBv?F?F?RF???7G&F????b&WF?&??6?W'2??F?V?G2v?F??7B??f&7F????bG?6gV?7F????"?b????????FV?2?b6&F??F???6?G??B??F?V?G2G&VFVBv?F??F?&7?6??W2???FF?F????F?RF???7G&F????b&?F?4R?2?B&WF?&??6?W'2?2FF?F?fR&V?Vf?6??VffV7G2??F?V?G2v?F??bG?6gV?7F????B&RF?R&V6???V?FVBG&VF?V?B??7W'&V?B42???bwV?FV??W2??W&R&R6??R?bF?R&V6V?B7GVF?W2??????rB&WfV?F??r?"F????6???rF?R6&F??F???2VffV7G2?b6?6W"F?W&?W2?(
???fW7F?vF?'2g&??F?R6?WfV??B6???2?B66RvW7FW&?&W6W'fRV??fW'6?G?Wf?VFVBF?RVffV7B?b6??F??V?W27FF??G&VF?V?B??FWfV???V?B?b?Wr???6WB?b??c#?F?V?G2v?F?'&V7B6?6W"&V6V?f??r?F?&7?6??R?&6VB6?V??F?W&??2??6?FV?B?b?B6?6W"?&V?FVB??'F?G?vW&R6?v??f?6?F???vW"??F?R7FF??w&?W?v?F????f?W"66W2?b?b??F?V?G2G&VFVBv?F?7FF??26??&VBv?F?#266W2??F?R6??G&??w&?W?FF?F??????F?W&RvW&RR6?6W"?&V?FVBFVF?2??F?Rw&?W??B&V6V?f??r7FF??2?6??&VBv?F???FVF?2??F?R7FF??w&?W????66????r6???V?F'??F??V????V????B?w&?FR?( ?????W"6???"F?F??WFW2G&????rF?&V6??R( ?f?Bf?"&GF?^( ??BW&f?&?BF?V?"V??7FF??2V"F?&R?V6W76'?6????V?Bf?"F?V?G2v?F?6?6W"F?&VG?F?V?6V?fW2f?"F?V?"6?6W"v"?( ?B(
???W"F?&RV&?6?VB???42???fW7F?vF?'2&W?'BF?R&W7V?G2?b???B&?F???VBG&??7VvvW7F??rF?BF?R6??&??F????bV??&???B6'fVF????&WfV?FVB?dTb&VGV7F?????F?V?G2v?F?F?fW'6R?V?F???v?6???v??6?W2V?FW&v???r??FV?6?fR6?V??F?W&??P??7V?V?F?fR??6?FV?6R?b?b?"6&F????F??GW&??rf?'7B2?V'2gFW"F?v??6?2'?6?6W"F?W&??D$?R????6?6W"F?V?G2?'6W'fVB7V?V?F?fR??6?FV?6R?V""?V'22?V'2?V""?V'22?V'2r?"R"?2Rb??Rr?RR2?2R??rP???F?&7?6??R?G&7GW?V?"???C3?b?BR#2??R#??"R#"?R32?"RC??P???F?&7?6??R???R?#Sr???G&7GW?V?"???C3r????F?W"6?V??F?W&????"?s"?r??R"?BRr?R??BR2?rR??"P?????R???3b?s???r?rR??RR?2R???RR?2R#?"P??R?rR#??rR#b?rRb?rR#2?"R3"?P??b??R"?Rb??Rr?R"??R??P??F?W7FVB7V?V?F?fR??6?FV?6P?????6&F??6?W&6Rv?&?D?Ww0??VwW7B#0??55t??44T???s2???FB???????2S????