Sen. Ted Kennedy weathered surgery to remove a good hunk of a malignant glioma in the left side of his brain on June 2 at Duke University Medical Center. His doctors tell us that after he heals a bit, he will embark on treatment combining radiation and chemotherapy. Surgery, radiation, and chemotherapy are common prescriptions for the million and a half people who find they have cancer each year. But in the small world of brain cancer—fewer than 20,000 people face this diagnosis yearly—using chemotherapy as a frontline treatment along with surgery and radiation is a relatively recent development.
The first new chemo agent for brain tumors in 20 years, Temodar (temozolamide), appeared on the scenes in late 1999. Developed by Schering-Plough, it gained expedited approval from the Food and Drug Administration because it was shown to more than double expected survival in patients with far-advanced malignant gliomas who had exhausted all other forms of treatment. With further proof of benefit, Temodar earned its way up to frontline therapy about three years ago and is now part of routine care.
Recognizing the power of chemotherapy in fighting gliomas has been long in coming. The drugs often have trouble getting into the brain because of the blood-brain barrier, a protective shield that keeps out many potentially toxic molecules. Chemo was a last resort, either when tumors came back or were found resistant to surgery and radiation. Then, a concoction of three drugs with the acronym PCV was the "rescue therapy." Occasionally, PCV worked.
Now we know that Temodar, started early and used along with and after radiation, can delay tumor recurrence and prolong life. The drug seems to make gliomas more sensitive to destruction by radiation. But it also can make tumors shrink without radiation, particularly tumors with a unique gene profile in which segments of two chromosomes are deleted. This discovery spurred research into the glioma genome and has led to a somewhat humbling but enlightening finding: Gliomas that look virtually identical under the microscope can have numerous genetic differences that signal very different tumor behavior and response to therapy.
Better understanding of abnormal gene behavior has ignited optimism in a field that is all too often grim. Abnormal genes can point to specific biochemical targets that make other chemo agents good bets. For example, some gliomas lack a different gene, which causes them to overproduce a protein called EGFR. New drugs that block this protein and are already approved for other cancers have produced dramatic shrinkage in some gliomas bearing that genetic error. And other genes are targets too, including ones that affect inflammation, blood vessel growth, and even vitamin A metabolism. Yes, some commonplace drugs like Celebrex (which blocks the COX-2 inflammatory pathway) and Accutane (an acne drug similar to vitamin A) might find themselves in a standard glioma treatment cocktail, depending on the nature of the tumor.
The particular type of malignant glioma and the chemotherapy the senator receives are matters between himself and his family, and his doctors. But people looking on and concerned for his welfare should see beyond the doom-and-gloom statistics. For one thing, they're based on statistical means, and no patient is an average. As important, they are based on yesterday's patients, not those of today and tomorrow.
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