S. Lew1,3, R. S. Chamberlain1,2,3 1Saint Barnabas Medical Center,Department Of Surgery,Livingston, NJ, USA 2New Jersey Medical School, Rutgers University,Department Of Surgery,Newark, NJ, USA 3Saint George’s University,School Of Medicine,True Blue, , Grenada
Introduction: Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in cancer therapy, which has been linked to varying degrees of treatment related hypertension (HTN). Current publications contain wide variations in the incidence and severity of sunitinib-related HTN. In addition, the HTN risk uniquely associated with two current mainstay sunitinib regimens, 37.5mg continuous dosing and 50mg 4 weeks on, 2 weeks off dosing, has not been well established. This study sought to determine the incidence of sunitinib-associated severe HTN, to stratify HTN risk based on the type of malignancy treated, and to investigate the dosage related risk of severe HTN.
Methods: A comprehensive literature search of PubMed, Google Scholar and the Cochrane Central Registry of Controlled Trials was completed. Keywords searched were ‘sunitinib’, ‘sutent’, ‘SU11248’, ‘hypertension’, and ‘clinical trial’. All clinical trials were analyzed for patient recruitment, intervention, and outcomes. Incidence and risk ratio (RR) were calculated with 95% confidence intervals.
Results: 61 single or double arm, phase II/III clinical trials involving 6,813 patients treated with sunitinib were identified. The incidence of sunitinib associated severe (grade 3-4) HTN was 6.5% (95% CI [4.9-8.6]; p<0.0001) among 4,311 patients in 50 clinical trials in which sunitinib monotherapy was used in a single arm trial or RCT. Among 4,433 Sunitinib treated in 18 RCTs, the risk of severe HTN in the treatment group was 5% compared to 2% in the control (RR 2.82, 95% CI [1.63-4.88]; p=0.0002). The risk of sunitinib associated severe HTN in RCC patients was not higher than the control (RR 1.38, 95%CI [0.64-2.96]; p=0.41) but it was significantly different from all other malignancies (p=0.05). The incidence and risk of severe sunitinib-associated HTN were not significantly different among breast cancer (BC) and non-BC, Gastrointestinal stromal tumor (GIST) and non-GIST, between 37.5mg continuous and 50mg intermittent dosage regimens, or when monotherapy and/or concomitant chemotherapy were used. Significant heterogeneity was found among identified trials with regards to underlying malignancies, dosage of the treatment, and duration of the treatment.
Conclusions: Sunitinib treatment is associated with a significantly increased risk of all- and high-grade HTN. The differences in dosing regimens or combinational chemotherapy with sunitinib did not yield significant hypertension risk reduction. Although adequately powered large studies are needed to further investigate the contributing HTN risk factors and ideal management or prevention, blood pressure should be carefully monitored in patients treated with sunitinib to prevent cardiovascular complications.
