Prospective Evaluation of Sunitinib-Induced Cardiotoxicity in Patients with Metastatic Renal Cell Carcinoma

Abstract

Purpose To prospectively evaluate cardiotoxicity risk with sunitinib in metastatic renal cell carcinoma (mRCC) routine clinical practice using comprehensive echocardiography and biomarker phenotyping. Patients and Methods In a multi-center prospective study of 90 mRCC patients, echocardiography and biomarkers of cardiovascular injury and stress were quantified at baseline, 3.5, 15, and 33 weeks following sunitinib initiation. These “on-drug” visits corresponded to cycles 1, 3, and 6, respectively. LV dysfunction was defined as an absolute decline in LV ejection fraction (LVEF) by ≥10% to a value of <50%. Conditional survival analyses predicted the risk of LV dysfunction. Linear mixed effects models estimated changes in LVEF, high-sensitivity Troponin I (hsTnI), and B-type natriuretic peptide (BNP) over time. Results The predicted risk of LV dysfunction by cycle 6 was 9.7% (95% CI 3,17%). The majority of events occurred in the first treatment cycle. This risk diminished to 5% and 2% in patients who had not experienced dysfunction by the completion of cycles 1 and 3, respectively. All evaluable patients who experienced LV dysfunction had subsequent improvement in LVEF with careful management. Six patients (6.7%) developed hsTnI elevations >21.5 pg/ml, and eleven additional patients (12.2%) developed BNP elevations >100 pg/ml. These elevations similarly tended to occur early and resolved over time. Conclusion On average, mRCC patients receiving sunitinib exhibit modest declines in LVEF and nonsignificant changes in hsTnI and BNP. However, approximately 9.7% to 18.9% of patients develop more substantive abnormalities. These changes occur early and are largely recoverable with careful management.

Cancer treatment associated cardiac toxicities

“…Studies regarding its safety profile are limited, however, one study noted modest decreases in LVEF of approximately 10%, with the majority of these effects occurring in the first treatment cycle. 43 Another study noted that 47% of patients developed new-onset hypertension as well. 44 However, these side effects were noted to be manageable with proper monitoring of both blood pressure and LVEF changes.…”

“…44 However, these side effects were noted to be manageable with proper monitoring of both blood pressure and LVEF changes. 43 …”

Sertraline/ICG‐loaded liposome for dual‐modality imaging and effective chemo‐photothermal combination therapy against metastatic clear cell renal cell carcinoma

“…However, due to poor biocompatibility (Wang et al, ) and lack of tumor targeting and specificity of these drugs, high systemic toxicity typically occurs. Some of these side‐effects include hypertension (Haddad & Rini, ; Kandula & Agarwal, ; Pham, Ye, & Pal, ), hematological and cardiac toxicity (Chu et al, ; Haas et al, ; Motzer et al, ; Narayan et al, ), hand–foot syndrome (Haddad & Rini, ; Pham et al, ), gastrointestinal effects (Santoni et al, ), and others. These adverse events can seriously compromise patients’ health, interrupting the treatment schedule and, thereby, reducing the overall survival and prognosis of these patients (Abshire et al, ).…”

“…hypertension (Haddad & Rini, 2012;Kandula & Agarwal, 2011;Pham, Ye, & Pal, 2015), hematological and cardiac toxicity (Chu et al, 2007;Haas et al, 2015;Motzer et al, 2007;Narayan et al, 2017), hand-foot syndrome (Haddad & Rini, 2012;Pham et al, 2015), gastrointestinal effects (Santoni et al, 2014), and others. These adverse events can seriously compromise patients' health, interrupting the treatment schedule and, thereby, reducing the overall survival and prognosis of these patients (Abshire et al, 2017).…”

Cabozantinib‐related cardiotoxicity: a prospective analysis in a real‐world cohort of metastatic renal cell carcinoma patients

“…It has become clear that VEGFRs‐TKIs have associated cardiotoxic effects, such as hypertension, asymptomatic left ventricular (LV) dysfunction, up to congestive heart failure (CHF) . The drug inhibition of tyrosine kinases normally expressed in non‐neoplastic tissues (including the myocardium and blood vessels) might be responsible for this toxicity.…”