Find out what your doctor is reading about this new colon cancer treatment.
By Laurie Barclay
Reviewed By Charlotte Grayson
Editor's Note: On Feb. 26, the FDA approved Avastin as an initial treatment for metastatic colorectal cancer (colorectal cancer that has spread to other organs). The drug is the first of its kind, targeting a growth factor that promotes the development of blood vessels that feed tumors. This blood vessel growth is called angiogenesis. Avastin inhibits this blood vessel growth. Thus, it's called an angiogenesis inhibitor. Studies show that the drug can delay tumor growth and prolong survival.
When given intravenously in combination with the standard chemotherapy treatment, Avastin prolonged survival by about five months.
To find out more about the potential role of Avastin in the treatment of colorectal cancer, WebMD's sister web site, Medscape, interviewed Herbert I. Hurwitz, MD, an assistant professor of medicine at Duke University in Durham, N.C., and a consultant for Genentech. Hurwitz has worked on trials of Avastin sponsored by Genentech as well as trials of other agents used for colorectal cancer sponsored by other pharmaceutical companies.
This article was written for health care professionals. If you have questions about it, print it out and take it to your health care provider.
Medscape: What is the mechanism of action of Avastin?
Hurwitz: For tumors to grow, they need a blood supply, and for blood vessels to grow, they need growth factors. VEGF appears to be one of the most important of these growth factors. [Avastin] appears to work by binding to the VEGF receptor and blocking signals for blood vessel growth. Without these signals, tumor blood vessels are stunted in their growth, causing a similar effect in the tumor itself. VEGF is the first growth factor shown to be effective in this fashion.
Medscape: How effective is Avastin in treating metastatic colorectal cancer?
Hurwitz: For patients with newly diagnosed metastatic colorectal cancer, [Avastin] represents a fairly big advance. This drug is able to prolong survival by about five months from a baseline median survival of 15.6 months for [patients who just received standard treatment] to 20.3 months for [those getting standard treatment plus Avastin].
This correlates with increasing survival by about one third. If a patient has 15 months' average life expectancy without this drug, and [Avastin] adds another five more months of good quality of life, this may be clinically relevant. This is as large a benefit as we've seen with any other treatment for colorectal cancer.
We still have far to go and we need to do better, but the addition of [Avastin] is a solid first step.
Medscape: What are the adverse effects of Avastin, and how does the safety profile compare with that of other available agents?
Hurwitz: Compared with most chemotherapy, the safety profile of [Avastin] appears quite favorable. In our study, [Avastin] caused a modest increase in blood pressure, and about 11% needed to use an oral antihypertensive medication. There were no hypertensive crises [a life-threatening rise in blood pressure] in our study.
There is a serious but rare event, which is the risk of gastrointestinal perforation [a hole or tear in the gastrointestinal tract]. This can occur in 2% to 3% of patients with colorectal cancer who are receiving any chemotherapy. In our study, there were six events in 400 patients in the [Avastin] arm, or a rate of 1.5%; however, no perforation events were seen in the control arm [the group that didn't get Avastin]. Of the six patients with perforation, three patients recovered and restarted treatment without any subsequent problems, two patients discontinued treatment permanently, and one patient died.
Overall, there was still a major survival benefit, but this risk needs to be respected for patients with issues related to bowel integrity [perforation], particularly those [who] would not have fit the eligibility criteria in our phase III trial. The effect is rare and often seen in the context of an overall clinical response, but it can be serious, so it needs to be respected and followed with close clinical management.
Medscape: How does Avastin compare with Erbitux, another new drug for metastatic colorectal cancer?
Hurwitz: These drugs really can't be well compared based on present data.
[Avastin] was used in the first-line setting [along with the initial chemotherapy], where it had a clinical benefit in response rate, overall survival, and time to progression of the cancer.
[Erbitux] was used in patients whose cancer progressed [while being treated with chemotherapy]. When retreated with Camptosar plus Erbitux, these patients had a benefit in response rate and time to progression of the cancer but not in overall survival.
To some degree, both drugs achieved some degree of tumor control and shrinkage, but in different settings.
Medscape: What do you anticipate will be the future role of angiogenesis inhibitors in cancer treatment?
Hurwitz: Our study validated the antiangiogenesis approach in cancer in general and in colorectal cancer in particular. The future clinical role of angiogenesis inhibitors, specifically anti-VEGF factors, needs to be driven by more clinical data. Fortunately, many of these studies are now ongoing or are being initiated.
Published April 26, 2004.
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