E-mail pageDrug Made from Scorpion Venom Keeps Patient’s Brain Tumor in Check
A drug derived from scorpion venom appears to be helping a 49-year old Tinley Park woman beat the odds. Diagnosed in December 2005, with a deadly glioblastoma multiforme, Donna Van Ryn has lived almost three times the median survival of 15 months--and feels fine.
She has been through two brain surgeries to remove her cancer, which oncologists suspect is the same type as the late Sen. Edward Kennedy’s. She went through aggressive radiation and chemotherapy, and two clinical trials of investigational drugs. But the treatment to which she is currently responding involves a medication fashioned from a scorpion’s sting.
Van Ryn says she now feels better than at any time since she noticed her first symptoms, and her scans show no evidence of recurrent disease. She walks three miles a day and just started a new job as a second-grade teacher. “I’m pretty much back to my normal self,” she says.
Arachnid Venom Targets Tumor Cells
The drug, known as I131-TM601, combines radioactive iodine (I131) with a piece of a toxin (TM601) derived from the venom of the Israeli desert scorpion (Leiurus quinquestriatus, ominously referred to as “deathstalker.”) The toxin fragment recognizes and binds to receptors found on the surface of glioma cells but not on normal, healthy cells.
It is given intravenously, enabling it to travel throughout the body and find the targeted tumor cells. It can cross the barrier that protects the brain from blood-borne toxins. Within the brain, it “shockingly homes right in on glioma cells,” said trial director Steve Chmura, MD, radiation oncologist at the University of Chicago Medical Center. “We often talk about targeted therapy, but this is far more targeted than most of what we see.”
“We found it remarkable how effective this therapy appears to be in this patient, who had progressed through multiple prior therapies and was thus less likely to respond to subsequent therapies,” said brain-cancer specialist Rimas Lukas, MD, instructor of neurology. “We were also impressed that it appeared effective after a limited number of doses. With most therapies for glioblastoma, we continue to treat indefinitely.”
“The big remaining question,” he added, “is why certain patients, such as Donna, respond for a prolonged time period and others do not.”
By itself, the toxin is thought to restrict tumor growth by preventing the proliferation of new blood vessels required by an expanding tumor. More important, it transports a lethal dose of radiation directly to cancerous cells. The radioactive iodine kills malignant cells but causes little damage to nearby healthy cells.
Van Ryn initially found the notion of introducing arachnoid venom into her brain somewhat unappealing. Those who have been stung by a scorpion emphasize the severe pain. Shakespeare has the anguished and guilt-ridden Macbeth cry out that his mind feels “full of scorpions,” but by the time the drug became available to Van Ryn, she had already been through a long, difficult struggle and was running low on options.
Road to Recovery
She was diagnosed almost four years ago, two days before Christmas, 2005. She had surgery to remove the tumor two days after Christmas, followed by standard post-operative treatment: chemotherapy with a drug called temozolomide (Temodar) and six weeks of radiation therapy. Her tumor soon grew back.
She had a second operation in May 2006, followed by 14 more months of chemotherapy, which seemed to keep the cancer at bay. By July of 2007 a smaller third tumor showed up on a follow up MRI, deep in the brain and close to the optic nerve. Additional surgery was out of the question since it had a high risk of brain damage or death and little benefit.
“At this point our doctors said we needed to start looking for clinical trials of new treatments,” said Van Ryn. “They transferred our care to the brain tumor team at the University of Chicago for investigational therapies.”
She initially enrolled in a clinical trial that combined irinotecan (Camptosar), a drug developed to treat colon cancer, with bevacizumab (Avastin), a promising agent that limits tumor size by preventing the growth of new blood vessels. Bevacizumab has since been approved by the Food and Drug Administration. This combination prevented tumor growth for about another 15 months, but the tumor developed resistance to both drugs and they became less effective. Fatigue had set in by August 2008, and she had to stop work for the foreseeable future. A November MRI showed the cancer was back.
So in December 2008, Van Ryn began treatment with I131-TM601. The first dose is very small and is used to make certain the treatment homes in on the tumor, transporting the radioactive iodine to the right spot. It did. She then received two larger treatment doses, one week apart.
Although the therapy targets tumor cells, it can have side effects including headaches, swelling of the brain, confusion, vision loss and fatigue. For Van Ryn, the fatigue, a common consequence of radiation to the brain, was the most severe. Her final dose left her “pretty weak,” she recalled, with some understatement. She spent most of the next few weeks in bed and required physical therapy to regain the strength to walk. She recovered slowly but steadily and by March, she was walking daily and increasing her distance. In late August she began her teaching job.
She is the third of four patients enrolled in this trial at the University of Chicago Medical Center, one of about 20 sites for this clinical trial and the first to treat patients. She is the first to present such a positive response. Although TM601 has shown promise in previous studies, this is the first glioblastoma trial to give the drug intravenously, rather than injecting it directly into the tumor.
Unfortunately, the drug is not currently available. Due to current economic conditions, the drug manufacturer has temporarily placed the trial on hold
Eight months after treatment, however, TM601’s poster-adult, Van Ryn, is thrilled to be back to work for the first time in over a year. She credits her recovery to the wonders of modern science, good luck and, especially, divine intervention.
“I guess God’s not quite done with me yet,” she suspects. “There must be a reason he wants me around.”
