Novel Therapy Offers ‘Glimmer of Hope’
To watch 10-year-old Joyce Wu busily padding around in her red slides in a playroom at Childrens Hospital Los Angeles, just two months after the doctors said her resurging neuroblastoma was terminal, is to understand their decidedly unclinical enthusiasm.
To hear the giggles when Dr. Clarke Anderson stops at the bedside and tickles her, or to read the harrowing adventure story she penciled the other day whose 10-year-old heroine goes on to live “happy ever after,” is to join the doctors in thinking of her as a “glimmer of hope,” as one of them put it.
They concede that it is too soon to declare total victory in her long battle with neuroblastoma, a relatively rare childhood cancer that is nonetheless among the deadliest. But a novel combination of drugs is making Joyce’s doctors buoyant. In addition to giving her melphalan, a standard chemotherapy agent, they have administered an experimental drug called BSO, which is intended to quash the tumors’ ability to become resistant to the other, primary drug.
Although BSO was invented decades ago, the Childrens Hospital study is the first time that it has been used in combination therapy against a childhood cancer, said Dr. C. Patrick Reynolds, head of therapeutic development there. “We think this is going somewhere,” he said of the new approach.
Despite its promise, BSO is a source of frustration to some medical researchers. The National Cancer Institute, which distributes the drug, tightly limits the supply.
Researchers at several medical centers are studying BSO--short for buthionine sulfoximine--in combination with other drugs against cancers of the skin, brain and ovaries. But there is “not enough of the drug around” to do the clinical testing that scientists would like to do, said Dr. Howard Bailey of the University of Wisconsin.
He is investigating BSO and melphalan in tandem against ovarian cancer and would like to combine BSO with other chemotherapies. But he said he is blocked from doing so by the institute’s regulations and the drug’s short supply, which he believes has slowed research on the compound over the last decade.
The cancer institute says that BSO is strictly limited to select researchers because the drug, which does not have Food and Drug Administration approval for any use, is very expensive to manufacture and is still unproved, said Dr. James Pluda, a medical researcher in the drug monitoring branch.
Researchers who believe that BSO may significantly boost therapies for cancers such as neuroblastoma, which strikes 500 to 600 children a year in the United States, will perhaps invoke Joyce Wu’s turnaround as evidence.
Back in September, the cancer had spread throughout her body to the point that 93% of her normal bone marrow cells were displaced by cancer cells, her doctors said. A tumor the size of a golf ball bulged beneath her scalp. Morphine did not erase the pain.
“Joyce had truly advanced disease, and for her to have undergone this kind of change is very startling,” said Anderson, a pediatric oncologist at Childrens Hospital and a member of the research team that has been treating her.
In their pilot study at Childrens, Reynolds, Anderson and Dr. Robert Seeger have treated 10 children with advanced neuroblastoma using the BSO-melphalan combination. Reynolds said six patients did not respond positively to treatment--indeed, one being tested at another hospital died of “unexplained” kidney failure--while four showed some improvement.
He said he did not know why some patients had no response to the drug or a poor one, but physicians remain concerned about the therapy’s potential side effects: Just as BSO appears to enhance melphalan’s ability to kill cancer cells, BSO may also boost its toxicity.
The end of the BSO shortage--and the cancer institute’s default monopoly--may be in sight. The Irvine-based cancer testing firm Oncotech, in partnership with a United Kingdom chemical company, is developing a new process of manufacturing pure BSO. Medical Director Dr. John Fruehauf, an oncologist who studied BSO at the National Cancer Institute, said the company may have a supply of BSO for clinical testing next year.
Like most cancers, neuroblastoma is a shifty foe, sometimes yielding to drug treatment--only to come back later, newly resistant to the very therapy that once thwarted it. BSO is like a biochemical wrench thrown into a tumor’s defense mechanism. After seeping into cancer cells, BSO blocks production of a biochemical, glutathione, that the cells use to dismantle certain chemotherapy agents such as melphalan.
Only 56% of patients are still alive five years after being diagnosed with neuroblastoma, a peripheral nervous system cancer. This compares to an average survival of 70% for all child cancers, according to the National Cancer Institute.
The experience of Joyce Wu, who has spent more than half her life fighting the disease, illustrates neuroblastoma’s wily nature. She was first diagnosed in 1991, when the family still lived in Taiwan. (The family moved to San Jose three years ago.) After a year of futile chemotherapy in Taipei, the doctor recommended Childrens Hospital Los Angeles, and since then she has undergone numerous treatments there and at a UC San Diego hospital.
By September, though, the cancer had spread throughout her body and bone marrow. “I almost gave up,” said her father, Kevin Wu, a software engineer at Phoenix Technologies in San Jose.
At the time, Joyce’s mother was pregnant, and Joyce asked her father if she would ever see the baby. “I said, ‘Of course.’ But in my mind I didn’t know,” he recalled.
By now she has received three of the four projected BSO-melphalan treatments. The racking aches have faded. Her scalp no longer bulges. And her bone marrow is practically free of cancer cells. Still, Seeger said, “she’s not out of the woods.”
Two weeks ago, her mother gave birth to a baby girl, Judy. In a letter to a friend that she composed before leaving the hospital Thursday night, Joyce wrote in that cockeyed, oh-so-determined fourth-grader’s script: “I’m fine at the hospital. I’m so excited to see the baby. The baby is so cute.”
