Sorafenib -- a new antineoplastic* drug used to treat patients with advanced renal-cell cancer (RCC) and hepatocellular cancer -- significantly increases the risk of developing hypertension, according to an Article to be published early Online and in the February issue of The Lancet Oncology. As such, patients given sorafenib need to be closely monitored, and treatment for hypertension to prevent cardiovascular complications is strongly recommended, say the authors.
Sorafenib is a multikinase inhibitor used to extend survival in patients with advanced RCC or hepatocellular cancer, and its efficacy in other cancers, such as non-small-cell lung cancer, prostate cancer, and melanoma, is undergoing clinical assessment. However, hypertension has been noted as a major side-effect of sorafenib in previous trials, with its incidence ranging from 16•0–42•6%. The detection of hypertension is important because early and aggressive management can prevent serious cardiovascular events, such as strokes and heart attacks as well as renal failure. Because of the limited number of patients in trials, the overall risk of hypertension with sorafenib is unclear.
Therefore, Dr Shenhong Wu (State University of New York, Stoney Brook, NY, USA) and colleagues did a systematic review and meta-analysis of clinical trials using the standard dose of sorafenib in patients with cancer to establish the incidence and overall risk of hypertension. Nine studies including 4599 patients published between January, 2006, and July, 2007, were selected from 223 eligible articles. The researchers noted a high incidence of all-grade hypertension (23•4%) in patients receiving sorafenib and an overall summary high-grade** incidence of 5•7%. No significant difference was noted between patients with RCC or a non-RCC malignancy. Furthermore, sorafenib was associated with a six-fold increased risk of developing all-grade hypertension compared with controls.
The authors conclude: "This study has shown that sorafenib is associated with a significant risk of developing hypertension. Early detection and effective management of hypertension might allow for safer use of this drug. The hypertensive and cardiovascular side-effects of sorafenib need thorough postmarketing surveillance and reporting, and future studies will be needed to identify the mechanism and appropriate treatment of sorafenib-induced hypertension."
Dr Shenhong Wu, State University of New York, Stoney Brook, NY, USA.
T) +1 631 638 0926 shwwu@notes.cc.sunysb.edu
Notes to Editors
*Antineoplastics are drugs that inhibit and combat the development of tumours.
**High-grade hypertension needs to be treated with more than one drug or with a more intense treatment than previously used (grade 3), or is associated with life-threatening consequences (grade 4). It can result in substantial morbidity, dose reduction, or discontinuation of sorafenib.
Journal
The Lancet Oncology