Cancer Patience

Can an experimental gene therapy effectively treat a malignant brain tumor? Doctors at Houston’s M.D. Anderson are taking it one day at a time.

IN NOVEMBER 1995, PAUL MADISON, a retired state tax examiner from Northport, Alabama, learned that the strange speech problems he had been having were the result of a brain tumor. Over the next several months, he began an exhausting schedule of radiation and chemotherapy. His wife, Alligene, who now has half a dozen spiral notebooks full of handwritten observations on his condition, accompanied him on every appointment. On April 12 the Madisons drove to the Kirkland Clinic at the University of Alabama in Birmingham to see whether the tumor’s rampant growth had been arrested. But Paul’s doctor gave them disheartening news: It was growing again. “It’s very aggressive,” he said. “It has changed quite a bit since the last scan.”

Before the appointment, the Madisons had read an article about suicide gene therapy, an experimental remedy that alters the genetic makeup of a tumor’s cells so that the tumor stops growing. In desperation the Madisons seized on the possibility that the therapy—which was being tested at several clinics around the country, including the University of Texas M. D. Anderson Cancer Center in Houston—might be Paul’s salvation. They didn’t have much time, because the kind of tumor that afflicted Paul is almost always fatal and grows very quickly, and his first symptoms had appeared eight months earlier. “Mother, pack your bags,” the Madisons’ daughter Denese said when she heard the test results from Birmingham. “We’re going to Houston in the morning.”

Paul, who is 68, began the treatment at M. D. Anderson in May, and since then, tests have shown no signs of growth in his tumor. The Madisons are convinced that he has been cured. They talk about gene therapy with the fervency of religious converts describing their faith—or rather, Alligene does, as Paul still has trouble speaking.

She …” Paul begins, and then he gets stuck.

Speaks for me?” Alligene asks.

He nods.

The good Lord opened the doors and windows for us,” says Alligene. “We are just so grateful that the tumor is not growing anymore.”

Yet Alfred Yung, the neuro-oncologist overseeing the clinical trial at M. D. Anderson, is more measured in his assessment of the therapy’s possibilities, for he knows firsthand that it doesn’t always work. Of the three patients in his care who received the treatment, only Paul Madison has survived. And that, in a nutshell, is the state of gene therapy today: wildly promising but still far from reliable. While the public seems to expect doctors to be able to fix chronic medical problems by tinkering with genetic material like a mechanic under the hood of a car, years of research need to be done before gene therapy fulfills its potential. Then again, if it can someday be perfected, it will indeed resemble a miracle—it will be an alternative for people who cannot be treated by more-conventional means.

Like most other patients who enter a clinical trial, Paul arrived at M. D. Anderson after a protracted ordeal. In his case the first indications that something was wrong were subtle; he had always been articulate, but about a year and a half ago he began having trouble saying some words. “I remember he had trouble with the word ‘pretty,’” says Alligene. “He would say ‘pity’ instead. He couldn’t get the r’s out. He more or less quit saying the word ‘refrigerator.’ He would just point at the refrigerator instead.”

The Madisons’ family doctor ran a battery of tests, but none of them revealed the cause of Paul’s problem. Finally, the doctor conceded that he couldn’t make a diagnosis and referred Paul to a neurologist, who ordered a magnetic resonance imaging ( MRI) scan of his brain. Before the results came back from the lab, however, Paul’s condition abruptly worsened. On September 24, 1995, at about eight in the evening, Alligene saw him go into the bathroom. She grew concerned when she heard the water run for a long time and a lot of splashing. “It sounded like a flood,” she says. Alligene discovered that Paul was washing his face over and over; for a brief period, he was unable to speak. “He could not say a single word. I could see in his face that he didn’t know what was happening to him.”

Alligene took Paul to the nearby Druid City Regional Medical Center, where the medical staff suggested that he had had a stroke. When the results of the MRI finally came back, Paul’s neurologist noticed a small mass in the left parietal lobe of his brain—an area that governs the ability to speak—but he assumed that it was scar tissue left over from a stroke that he decided Paul must have suffered in the past, causing his initial speech problems. Then, several days later, Paul experienced another episode similar to the one that had sent him to the hospital; his face started twitching, and he couldn’t speak. This time, doctors recognized the occurrence for what it was—a seizure—but still thought the underlying problem was a stroke.

It wasn’t until November, when Paul was referred to the Kirkland Clinic, that his illness was correctly diagnosed. Stroke specialist Thomas Head discovered that an unusual amount of oxygen was being absorbed from Paul’s blood in the vicinity of the mass that the doctors in Druid City had found. In other words, the mass was growing, so it couldn’t be scar tissue. Head sent Paul to see a second specialist, Stephen Rosenfeld, who confirmed the presence of a tumor. After another MRI scan showed signs of further growth, a neurosurgeon performed a biopsy, and the findings were grim: Paul had a glioblastoma, the most malignant type of brain tumor. Because of the tumor’s location, however, surgery wasn’t an option; and even if it had been, there was no guarantee that all of the cancer could have been removed—glio-blastomas are fiercely tenacious. So that December, Paul began radiation and chemotherapy. For thirty consecutive weekdays, he drove to Druid City for the treatments. In February the Madisons were elated to learn that an MRI

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