Sorafenib, a new anti tumour (antineoplastic) drug marketed by Bayer under the brand Nexavar, and used to treat patients with advanced kidney or liver cancer, has been found to increase significantly the risk of developing high blood pressure.
This was the main finding of a study published in the early online version of the February issue of The Lancet Oncology that was carried out by Dr Shenhong Wu from State University of New York at Stoney Brook, New York, and colleagues.
The researchers recommend that patients on this drug be closely monitored for signs of high blood pressure.
Sorafenib has been shown to increase survival in patients with advanced renal-cell carcinoma (RCC, the most common form of kidney cancer) and hepatocellular carcinoma, or primary liver cancer. It is also being tested on patients with non-small-cell lung cancer, prostate cancer, and melanoma.
Sorafenib is a multikinase inhibitor, which means it slows down and attacks tumour growth by interfering with the signals used by a range of proteins to control cancer cell division and proliferation.
Unfortunately one of the drug’s side effects is elevated blood pressure, which other trials have shown can affect between 16 and 43 per cent of patients.
It is very important that any sign of this high blood presure side effect is found early, because its timely and aggressive treatment can prevent serious heart attacks and strokes, as well as kidney failure.
So far, it has not been possible to assess the overall risk of elevated blood pressure for sorafenib patients because the number of participants on any one trial has not been enough.
However, by pooling the results of clinical trials that included cancer patients on sorafenib, Shenhong Wu and colleagues were able to assess, using a method called meta-analysis, the overall incidence and risk of high blood pressure linked with the drug.
They searched Medline, Web of Science, and abstracts presented at the American Society of Clinical Oncology, and found 223 potential studies published between January 2006 and July 2007, of which 9, covering around 4,500 patients, met their selection criteria.
To be included in the pooled results, eligible studies had to be prospective clinical trials of patients with cancer assigned single-drug sorafenib at a dose of 400 mg twice a day, and have information on blood pressure measures.
The analysis showed :
- 23.4 per cent of patients on on sorafenib had all-grade hypertension.
- This compared with a summary overall high-grade incidence of hypertension of 5.7 per cent.
- There was no significant difference between patients with RCC and non-RCC cancer.
- Compared with patients who did not take the drug, patients on sorafenib had a six-fold increased risk of developing all-grade hypertension.
The researchers concluded that:
“This study has shown that sorafenib is associated with a significant risk of developing hypertension.”
They suggested that early screening and timely management of high blood pressure might allow sorafenib to be used safely.
They recommended that clinical use of the drug is closely monitored for side effects such as high blood pressure, heart attacks and strokes, and that more studies are needed to find out how the drug causes high blood pressure and the best way to treat it.
High-grade hypertension (grade 3) usually needs more than one drug or a more intensive dose. Without intensifying treatment it leads to life-threatening consequences (grade 4).
“Incidence and risk of hypertension with sorafenib in patients with cancer: a systematic review and meta-analysis.”
Shenhong Wu, John J Chen, Andrzej Kudelka, Janice Lu, and Xiaolei Zhu.
The Lancet Oncology Early Online Publication, 22 January 2008.
DOI:10.1016/S1470-2045(08)70003-2.
Sources: The Lancet Oncology journal article and press release.
Written by: Catharine Paddock