Brain cancer in its sights
TREATMENT options for the deadliest type of brain cancer are so limited that most people don’t live more than 15 months after their initial diagnosis. An experimental therapy may eventually help turn this bleak picture around.
The new drug singles out and destroys the malignant cells of this lethal cancer, known as a glioblastoma, similar to a heat-seeking missile locating a target.
The chemical “is the next step toward making significant advances in battling this disease,” says Dr. John S. Yu, a neurosurgeon at Cedars-Sinai Medical Center in Los Angeles who is testing the drug.
About 60% of the 17,000 people diagnosed with brain cancer each year are stricken with glioblastoma. Although medical science has made great strides in the treatment of many other cancers, survival rates for this highly aggressive brain cancer have increased by only nine months since the 1960s. Devising effective treatments has proved daunting.
First, these types of brain cancer cells spread beyond the original tumor sites and proliferate throughout the brain, mixing with normal cells. This makes it difficult to surgically remove or kill all the cells with radiation and chemotherapy without harming healthy tissue. As a result, tumors quickly grow back.
The biggest hurdle, however, is getting drugs past the blood brain barrier, the specialized network of tiny blood vessel cells that protects the brain from harmful substances in the bloodstream. “Even if we had good drugs, we couldn’t get them into the brain,” says Dr. Sandeep Kunwar, a neurosurgeon at UC San Francisco Medical Center, who is testing this new drug.
Known as IL13-PE38QQR, the targeted therapy is designed to circumvent these obstacles. It is programmed to home in only on glioblastoma cancer cells, and is surgically infused directly into the brain to deliver high concentrations of the medicine.
The drug is made of a fusion protein, which combines the human protein Interleukin 13 (IL 13) with a fragment of a bacterial toxin protein, Pseudomonas exotoxin (PE), says Dr. Raj K. Puri, a geneticist at the Center for Biologics Evaluation and Research at the Food and Drug Administration in Rockville, Md.
The IL13 portion latches on to receptors on the surface of the glioblastoma cells -- and only on the cancer cells -- and then releases its lethal payload.
“The IL13 binds to the cancer cell’s receptors, which are like chemical docking sites, and is absorbed by the cell,” says Puri, who helped develop this fusion protein. “But the cells are fooled because they don’t know there is a toxin attached, and die.”
The drug is delivered through two to four catheters surgically inserted inside the patient’s brain. A pump slowly pushes the drug solution through the catheters over a period of four days while patients are hospitalized.
Early studies on 36 terminally ill patients have been encouraging. The participants had exhausted standard treatments -- surgery to remove the tumors, radiation and the chemotherapy Temodar -- and had had at least one recurrence. Typically, median survival rates for these patients are four to six months, and less than 5% live past 18 months.
In contrast, the median survival rate for the study participants has been 45 weeks. Of the 36 patients in the original study, nine are alive one to four years later, and eight of them are cancer free. “This is well beyond anything we’ve ever seen in the past,” Kunwar says.
A larger test of the therapy was launched in early 2004 at more than 50 medical centers in the U.S., Canada, Europe and Israel. The study will eventually involve 300 patients who have failed traditional therapy and whose cancer has recurred. Two hundred patients will receive one treatment of IL13-PE38QQR, while the remainder will be treated with a Gliadel wafer, an anti-cancer drug that is surgically inserted inside the brain.
Scientists hope to complete enrollment by the end of this year and have follow-up test results by 2007, said Lawrence A. Kenyon, chief financial officer of NeoPharm Inc., the Lake Forest, Ill., company that makes the drug.
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Other options
Two other treatments for glioblastoma are also showing particular promise.
One, called TransMID, is similar to IL13-PE38QQR in that it fuses a protein with a deadly toxin. This drug combines a protein called transferrin, which attaches itself to the cancer cells, and a diphtheria toxin, which then kills the malignant cells. The drug is in the final phase of clinical trials that will encompass 323 patients at 24 test sites in the U.S.
The other promising treatment is a dendritic cell vaccine that prompts a patient’s immune system to dispatch cancer-killing immune cells to the tumors. A 2004 test of 14 patients indicated their median survival rate was about 2 1/2 years versus about 7 1/2 months for a comparable untreated group. A larger clinical trial that’ll eventually involve about 50 patients is ongoing at Cedars-Sinai Medical Center.
