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A Daring Treatment, a Little Girl’s Survival

In the pages of a medical journal, Melanie Joy McDaniel is a study subject, listed by her patient number and tumor type. In real life she’s a little girl whose story is a reminder that medical research can change lives and that the pioneers include patients, some of whom are babies.
Melanie was 9 months old when her parents faced an agonizing decision. She had already had two operations for a malignant brain tumor, and doctors could not be sure they had removed all the cancer. She needed more treatment, but standard chemotherapy offered little hope in exchange for its harsh side effects. And yet the McDaniels knew that if they did nothing, the odds were high that the tumor would come back.

Doctors at the Dana-Farber Cancer Institute in Boston offered another option, an experimental treatment. To qualify, a child had to have a progressive cancer, and it had to be terminal. The McDaniels took a gamble and a leap of faith, and signed Melanie up.

“It won’t save her, but it may help other people,” her father, Paul McDaniel, told me in an interview for a Science Times article published in April 2002. Then he paused and added, “Maybe it will save her.”

By then, Melanie had been receiving the test therapy for five months, and her brain tumor, a type called an ependymoma, had not grown. That was encouraging, but the treatment still seemed like a long shot.

After the article was published, I was afraid to call the McDaniels again. I didn’t think Melanie would survive.

Recently, Mr. McDaniel sent me an e-mail message. “Melanie is now 7 years old, attending first grade, and doing very well,” he wrote. “The doctors told us last year that they do not see any residual tumor in her brain. Their original diagnosis was that her tumor had no known cure.”

What had prompted him to get in touch was the death on Jan. 14 of Dr. Judah Folkman, the researcher at Dana-Farber whose work had led to Melanie’s treatment. Mr. McDaniel wrote that he wanted “to celebrate the accomplishments of Dr. Folkman, who faced resistance on his ideas that, by the grace of God, cured my daughter of an incurable brain tumor.”

Dr. Folkman founded a branch of research based on the theory that tumors need a blood supply in order to grow and can stimulate the formation of new blood vessels — angiogenesis — to feed themselves. If angiogenesis could be stopped, he reasoned, it might be possible to starve tumors. His work ultimately led to useful treatments but took years to gain acceptance in a field that was focused on attacking cancer cells directly.

Melanie McDaniel became one of 20 children with advanced cancer who were enrolled in a study that used drugs strictly to fight angiogenesis. The drugs included two standard anticancer medicines, but in small doses meant to stop blood vessels from forming, not the much bigger amounts needed to poison tumor cells.

The children also took two other drugs that had been found to block angiogenesis. One was Celebrex, usually given for pain and inflammation. The other was thalidomide, notorious for causing stunted limbs and other birth defects when pregnant women took it in the 1960s — damage, it was later learned, that the drug inflicted by halting the growth of blood vessels in the fetus.

Melanie and the other children were given small doses of medicine by mouth every day, instead of big doses intravenously every few weeks. The idea was that continuous treatment might keep blood vessel growth in check, whereas the usual schedule of therapy every few weeks could give new vessels a chance to sprout between doses. Doctors also hoped that the small doses would minimize side effects. The approach is called metronomic, low-dose or antiangiogenic chemotherapy.

“Our goal was to see whether we could keep the kids alive for an additional six months,” said Dr. Mark W. Kieran, Dana-Farber’s director of pediatric medical neuro-oncology.

The study was meant to test the feasibility of using the drugs for 26 weeks. But by the 26th week, seven children were doing so well that their parents refused to give up the drugs.

“Remember, you got onto this trial because your child had a progressive, incurable tumor,” Dr. Kieran said. “Many families said, ‘Why would we stop?’ ”

The McDaniels kept Melanie on the drugs for a year and a half. Then, she was monitored closely with M.R.I. scans.

Finally, last year, her doctors said there were no traces of the tumor left.

Mr. McDaniel said, “She goes to the survivor clinic now, instead of the pediatric brain tumor clinic.”

But the researchers are not claiming credit for Melanie’s recovery. The study was designed primarily to test the drugs’ safety, and it was not large enough to measure their effectiveness.

Dr. Christopher D. Turner, director of pediatric neuro-oncology outcomes research at Dana-Farber, said the surgery might be responsible, but he added: “Her type of tumor almost always comes back. Historically, we know that surgery alone is not usually enough.”

Every doctor encounters “miracle patients” who improve against all odds, Dr. Kieran said. But he also said, “We have a bunch of long-term survivors.”

A report on the study published in 2005 showed that seven children, including Melanie, were still alive a year and half to three years after starting the treatment.

“It’s immensely gratifying,” Dr. Turner said. “The study we did took the drugs we knew are commercially available and combined them in a way that hadn’t been used before. A number of doctors across the country have followed the published paper we did, the regimen, on their own patients, and have given us feedback that they have had some remarkable stories themselves across the country. We have to be careful — it’s not science; it’s anecdote. When someone calls and says, ‘We had a great response,’ what I don’t hear is how many others used it and didn’t have a good response.”

The next step is a larger study. One is already under way, involving 160 children at 12 medical centers, with eight categories of cancer.

“We certainly hope to have some answers within the next couple of years,” Dr. Turner said.

Meanwhile, Melanie, who has an older brother and a younger one and a lot of friends, is a normal little girl whom her mother describes simply as “hilarious.” But her parents know that her type of tumor can always recur, even after many years.

“As much as we’re excited about how good she’s doing, there’s that much fear of it coming back,” said her mother, Amy McDaniel. “It’s always in your mind.

“We need the science to keep going. We need to be armed and ready if it does return.”

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