According to results recently published in The New England Journal of Medicine, Avastin™ (bevacizumab) delays time to cancer progression in metastatic clear-cell renal carcinoma.
The kidneys are a pair of bean shaped organs located on each side of the spine. The kidneys filter the blood and eliminate waste in the urine through a complex system of filtration tubules. All of the blood in the body passes through the kidneys approximately 20 times an hour. Renal cell cancer is an uncommon form of cancer that is most often characterized by the presence of cancer cells in the lining of the filtration tubules of the kidney. Metastatic renal cell cancer (RCC) refers to cancer that has spread from the kidney to distant and/or several sites in the body. Standard treatment for metastatic RCC often includes immunotherapy agents such as
Proleukin® or alfa-interferon which stimulate the immune system to help fight the cancer. When patients stop responding to standard therapies, they are left with few effective treatment options. Clear-cell renal cancer is a type of kidney cancer that is usually caused by a mutation in a gene called the von Hippel-Lindau tumor suppressor gene. A mutation in this gene is associated with the overproduction of vascular endothelial growth factor, an important component of angiogenesis.
The inhibition of angiogenesis has become a major focus and well-studied topic in recent cancer research. Cancer cells require food, oxygen and growth proteins in order to grow and spread. These essential nutrients are transported to the cancer cells by blood vessels. Angiogenesis is the process of creating new blood vessels necessary to transport “food” to the cancer cells. Two key proteins that are necessary for the process of angiogenesis are called matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF). VEGF causes endothelial cells (cells comprising the innermost layer of blood vessels) to replicate and migrate from existing blood vessels to the cancer. Endothelial cells secrete MMPs, which create an opening in existing tissues surrounding the cancer, allowing the endothelial cells to move near the cancer and form new blood vessels to “feed” the cancer.
Avastin™ is a novel angiogenesis inhibitor that has completed the last phase of clinical trials prior to FDA approval. Avastin™ produces its anti-angiogenic effects by inhibiting the action of VEGF which halts the growth of new blood vessels necessary to promote and maintain cancer cell growth. It has demonstrated anti-cancer activity in the treatment of various cancers and is presently being evaluated in several clinical trials.
Researchers affiliated with the National Cancer Institute recently conducted a clinical trial to evaluate Avastin™ in the treatment of metastatic clear-cell renal carcinoma. This trial involved 116 patients, the majority of whom had cancer that was progressing. The patients were treated with either high-dose Avastin™, low-dose Avastin™ or a placebo (inactive substitute) every 2 weeks and were directly compared. Overall, patients treated with high-dose Avastin™ had the longest progression-free survival, compared with the other two groups. The average duration of progression-free survival at 4 months following initiation of therapy was approximately 64%, 39% and 20% for those treated with high-dose Avastin™, low-dose Avastin™ and placebo, respectively. Eight months following initiation of therapy, progression-free survival was approximately 30%, 14% and 5% for those treated with high-dose Avastin ™, low-dose Avastin™ and placebo, respectively. There were no differences in overall survival; however, longer follow-up may be necessary to reveal differences in overall survival between these 3 groups of patients. Avastin™ was well tolerated, with mild to moderate high blood pressure and protein in the urine being the most common side effects.
The researchers concluded that Avastin™ delays time to cancer progression in patients with metastatic clear-cell renal carcinoma and is easily tolerated. Longer follow-up is necessary to determine if Avastin™ improves long-term survival in this group of patients. Patients with advanced clear-cell renal carcinoma may wish to speak with their physician about the risks and benefits of participating in a clinical trial further evaluating Avastin™ or other promising therapeutic approaches.
Reference: Yang J, Haworth L, Sherry R, et al. A Randomized Trial of Bevacizumab, an Anti–Vascular Endothelial Growth Factor Antibody, for Metastatic Renal Cancer.
The New England Journal of Medicine. 2003;349:427-434.