Sunitinib and cardiac failure - are we cautious enough? A case report.

E. Connor¹, A. Brown², A. Michael³. ¹St Georges Medical School, London, United Kingdom, ²Liverpool, London, United Kingdom, ³Oncology, Royal Surrey County Hospital, London, United Kingdom.

Background and Aims: Renal cell carcinoma (RCC), the most common kidney cancer, accounts for 90-95% of primary malignant kidney tumours. RCC has a poor prognosis with only 8% of grade 4 patients surviving more than 5 years^[1]. Sunitinib, a tyrosine kinase inhibitor (TKI) has transformed the management and prognosis of RCC, however, reports have found a significant association with sunitinib administration and cardiotoxicity. The clinical significance of this is unclear and must be defined before rationalizing cardiovascular management during sunitinib administration. This case report aims to clarify the controversy around whether cardiac monitoring should be included in protocols for patients who are administered sunitinib by illustrating the severity, unpredictability and reversibility of sunitinib-induced cardiotoxicity.

Summary and Outcomes: 71-year-old Caucasian man with metastatic RCC developed congestive cardiac failure, requiring admission to the intensive care unit 41 days after commencing sunitinib therapy. His past medical history included clear cell RCC (managed with a right total nephrectomy thirteen years previously), hypertension, glaucoma and cataracts. He had no other cardiac history. CT scans illustrated pulmonary oedema and significant cardiomegaly. Bilateral pleural effusions and interstitial shadowing were also noted. Echocardiogram results demonstrated dilatation of the left ventricular cavity with a moderate decline in left ventricular ejection fraction (LVEF), global hypokinesia and mild regurgitation of all valves. Additionally, elevated troponin was detected. Sunitinib was discontinued. Consequently, his condition rapidly improved and within 2 months his echocardiogram results returned to normal.

Discussion: The clinical impact of sunitinib-induced cardiotoxicity has been well documented. This case is of particular interest due to the rapidity and severity of symptom progression but also the rapidity of malignant response. This introduces the concept that the level of response and toxicity may be intrinsically linked. Here discontinuation of sunitinib therapy and commencement of cardiac management led to reinstatement of normal baseline function. There is a heavy debate regarding the appropriate cardiac management during sunitinib administration. Including guidelines such as a dose reduction, a period of sunitinib withdrawal or cardiac medication introduction such as ACE inhibitors, angiotensin II blockers or beta blockers may be beneficial to prevent severe cardiotoxicity.

Conclusion: Avoiding cardiotoxicity whilst maintaining the anti-tumour properties of sunitinib is crucial. Whilst individual clinical discretion remains prudent, the utility of routine LVEF or cardiac biomarker monitoring in asymptomatic individuals remains unclear.

References:

Kollmannsberger C et al. (2007) Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects. Can Urol Assoc J [Internet]. http://www.ncbi.nlm.nih.gov/pubmed/18542784