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Clinical Trial Results

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  • Posted: 04/02/2008

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Sorafenib Increases the Risk of High Blood Pressure

Key Words

Solid tumors, sorafenib (Nexavar®), antiangiogenesis, hypertension. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)

Summary

Combined data from nine studies showed that patients receiving the standard amount of sorafenib (Nexavar), an anticancer drug that interferes with a tumor’s blood supply, run a significant risk of high blood pressure (hypertension). Doctors should closely monitor these patients during treatment and prescribe anti-hypertension drugs as needed.

Source

Lancet Oncology, published online January 24, 2008; in print Feb. 2008 (see the journal abstract)
(Lancet Oncol. 2008 Feb;9(2):117-23. Epub 2008 Jan 24)

Background

The targeted drug sorafenib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced renal cell carcinoma—a type of kidney cancer—and has also been shown to increase survival for patients with advanced liver cancer. Researchers are currently testing sorafenib for the treatment of many other types of cancer, including non-small-cell lung cancer, prostate cancer, and melanoma.

Sorafenib targets the growth of tumor blood vessels (such growth is called angiogenesis). Clinical trials of other drugs that target angiogenesis have shown that they can increase the risk of hypertension and, though rarely, heart attacks and other serious cardiac events. While hypertension has been noted among patients taking sorafenib, the condition’s incidence varied widely between different clinical trials. To get a more accurate estimate of how many patients taking sorafenib may experience hypertension, investigators needed to combine the results from individual trials.

The Study

Investigators from the State University of New York in Stony Brook combined data (called a meta-analysis) from nine prospective clinical trials testing sorafenib for the treatment of solid cancers, including kidney, liver, and prostate cancers as well as melanoma. They found these nine trials by searching databases of the medical literature (for papers published between 1966 and 2007) and conference proceedings from the American Society of Clinical Oncology (between 2004 and 2007) for clinical trial results presented in English.

All trials included in the meta-analysis assigned patients a starting dose of 400 mg sorafenib twice daily, which is the current starting dosage approved by the FDA, and provided data on hypertension observed during the trial.

The study’s lead author is Shenhong Wu, M.D., from the Division of Medical Oncology at the State University of New York in Stony Brook.

Results

From the nine studies, 4,599 patients were available for analysis: 3,567 received sorafenib and the other 1,032 served as controls. All the studies graded hypertension on a four point scale, from grade 1, which does not require treatment, to grade 4, which is considered immediately life threatening and can require treatment with multiple drugs and possible discontinuation of sorafenib.

Data on all grades of hypertension was available from 3,363 patients enrolled in seven trials. The overall incidence of all grades of hypertension was 23.4 percent in patients receiving sorafenib. Patients taking sorafenib were approximately six times as likely as patients not taking sorafenib to develop any grade of hypertension.

Data on high-grade hypertension was available from all 3,567 patients in the nine trials who received the drug. The overall incidence of high-grade (grade 3 or 4) hypertension was 5.7 percent for these patients.

Interestingly, patients with kidney cancer were not at higher risk of hypertension than patients with other types of cancer. Since the kidneys play a key role in regulating blood pressure, the investigators had been concerned that sorafenib might pose a greater risk for people with reduced kidney function.

Limitations

The investigators acknowledge that their study could have either overestimated or underestimated the incidence of hypertension. Data was not available on baseline hypertension (how many patients had hypertension at the start of the studies), which could cause overestimation of new cases of high blood pressure. On the other hand, the scale used to measure hypertension may have counted some patients with lower-grade hypertension as not having the condition, leading to an overall underestimation.

Comments

“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,” conclude the authors. In particular, they explain, further studies need to identify the classes of antihypertensive medications that can be safely given along with sorafenib, to minimize potential drug interactions and possible interference with the effectiveness of sorafenib.

"All medications have a risk/benefit ratio,” says Alison Martin, M.D., senior investigator with the National Cancer Institute’s Cancer Therapy Evaluation Program. “If sorafenib is considered important treatment for a patient, the medical caregivers can discuss the possibility of hypertension, assess any changes in blood pressure while on medication, and implement antihypertensives if needed."

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