Pantaleo et al. BMC Cancer 2012, 12:231 http://www.biomedcentral.com/1471-2407/12/231 associated tumor thrombus of the inferior vena cava and right atrium. He underwent right radical nephrectomy and tumor thrombectomy performed under extracorpor- eal circulation. Cardiac function was investigated, in- cluding coronary angiography and transthoracic and transesophageal echocardiography. These studies docu- mented normal cardiac function and normal morph- ology of the coronary arteries. Pathological examination of the surgical specimens demonstrated pT3cN0Mx con- ventional (clear cell) renal carcinoma, Fuhrman Grade 3 with negative surgical margins. A regular follow-up pro- gram was started. A few months later, hepatic and contralateral renal metastases were detected. The patient started treatment with the tyrosine kinase inhibitor (TKI) sorafenib on a dose-escalation protocol. Treat- ment led to an initial partial response followed by stable disease for 6 months. During December 2008, in a set- ting of stable disease, he underwent hepatic resection and enucleation of the left renal mass. The hepatic and renal masses were confirmed to be metastases. Early radiological assessment after surgery showed no residual hepatic or renal disease, but possible involvement of the mesenteric lymph nodes. Sorafenib treatment was there- fore restarted at a standard dose of 800 mg/day. Treat- ment led to complete disease response within a few months, and was very well tolerated by the patient, who did not experience any of the typical adverse effects of the drug. During February 2011, after 30 months of sorafenib treatment (6 months at 1600 mg/day and 24 months at 800 mg/day), the patient started to complain of worsen- ing chest pain precipitated by normal physical exercise. A cardiac stress test showed exercise-induced ischemia. Coronary angiography showed critical sub-occlusion of the common trunk of the left coronary artery and the circumflex artery (Figure 1). The patient subsequently underwent triple coronary artery bypass surgery and is now recovering and in good clinical condition. Sorafenib treatment has been discontinued. Discussion TKIs are currently approved for the treatment of mRCC [1,2]. Sorafenib is a multikinase inhibitor, with activity against transmembrane KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-B receptors, and intracellular CRAF and BRAF receptors. These kinases are involved in several angiogenesis systems and intracellular signaling pathways, and their disruption is aimed at inhibiting tumor growth [12]. The clinical efficacy of Sorafenib in the treatment of mRCC was demonstrated in a randomized, double-blind, placebo-controlled, phase III trial (TARGET) involving 903 patients who were resistant to previous therapy. An interim planned analysis of progression-free survival (PFS) showed a statistically significant benefit of sorafenib Page 2 of 5 Figure 1 Coronary angiography showing critical sub-total occlusion of the common trunk of the left coronary artery and circumflex artery. treatment over placebo (5.5 vs 2.8 months, p < 0.001). Consequently, a crossover was permitted from placebo to sorafenib. The difference in overall survival time was not statistically significant (19.3 vs 15.9 months), which can be explained by an important crossover effect. There was, however, a 28% reduction in the risk of death in patients receiving sorafenib [5,13]. Sorafenib may also be a suitable alternative treatment for selected naïve patients with clear cell mRCC [3]. A recent multicenter retrospective analysis of sequential treatment with sorafenib and suni- tinib showed that initial treatment with either agent was associated with similar PFS times during first-line treat- ment (median PFS 8.4 months with sorafenib vs 7.8 months with sunitinib; p = 0.758). However, patients treated with sorafenib and then sunitinib appeared to have a slightly longer PFS times during second-line treat- ment than those treated with sunitinib and then sorafe- nib (median PFS with second TKI: 7.9 months vs 4.2 months; p < 0.001) [14]. Common toxicities due to sorafenib treatment include reversible skin rashes, hand-foot skin reaction, diarrhea, hemorrhage, hypertension, and laboratory findings such as leucopenia, hypophosphatemia, and elevated pancre- atic enzyme levels [3,4]. Previous reports suggest that cardiotoxicity is a rare side-effect of sorafenib [4,5]. Some studies have commented on the cardiovascular toxicity of TKIs and monoclonal antibodies, in particular tumor angiogenesis inhibitors [6–8,15–18] (Table 1). The clinical events associated with cardiotoxicity include hypertension (8-45 % overall; 4-16 % grades 3 or 4) [3],