For the melanoma patients who signed on to try a drug known as PLX4032, the clinical trial was a last resort. Their bodies were riddled with tumors, leaving them almost certainly just months to live.
But a few weeks after taking their first dose, nearly all of them began to recover.
Lee Reyes, 30, of Fresno, Calif., who had begun using a feeding tube because of a growth pressing against his throat, bit into a cinnamon roll.
Nothing, he told his mother, had ever tasted as good.
Rita Quigley, who had been grateful just to find herself breathing each morning since learning she had the virulent skin cancer, went shopping for new clothes with her daughters at a mall in Huntsville, Ala.
Randy Williams, 46, who drove 600 miles from his home in Jonesboro, Ark., to the M.D. Anderson Cancer Center in Houston to get the experimental drug, rolled out of bed. "Something's working," he thought, "because nothing's hurting."
It was a sweet moment, in autumn 2008, for Dr. Keith Flaherty, the University of Pennsylvania oncologist leading the drug's first clinical trial. A new kind of cancer therapy, it was tailored to a particular genetic mutation that was driving the disease, and after six years of disappointments his faith in the promise of such a "targeted" approach finally seemed borne out. His collaborators at five other major cancer centers, melanoma clinicians who had tested dozens of potential therapies for their patients with no success, were equally elated.
In a kind of "pinch me" exercise, the six doctors sent one another "before and after" CT scans of their patients.
One was of Mark Bunting, 52, an airline pilot in Sandy, Utah. His initial scan in early October showed the cancer in his bones, an incursion considered virtually impossible to reverse. After two months on the drug, it had all but disappeared.
"Holy Cow!" Dr. Flaherty typed in reply to the slide from Dr. Antoni Ribas at the University of California, Los Angeles, that Dec. 17.
"Are you sure it is the same patient??" added Dr. Jeffrey A. Sosman at the Vanderbilt-Ingram Cancer Center in Nashville.
From New York, Dr. Paul B. Chapman of Memorial Sloan-Kettering Cancer Center, perhaps the most determined skeptic of the group, acknowledged, "This looks impressive."
The trial of PLX4032 offers a glimpse at how doctors, patients and drug developers navigate a medical frontier as more drugs tailored to the genetic profile of a cancer are being widely tested on humans for the first time.
Throughout the fall, the only two patients on the trial whose tumors continued to grow were the ones who did not have the particular gene mutation for which the drug had been designed. They were removed from the trial. By late December, tumors in the 11 patients who did have the mutation had shrunk. Those involved in the trial held their collective breath waiting to see how long the remissions would last.
It was a far cry from where they had been a year earlier, when a previous incarnation of the drug had no effect. Urged on by Dr. Flaherty and Dr. Chapman, the companies that owned it had spent months devising a new formulation that could be absorbed at higher doses.
But the new drug, still in the earliest phase of testing, had to pass several more hurdles before federal regulators would determine whether it was safe and effective enough for widespread use.
In December, as the doctors added more patients to the Phase 1 trial, looking for the highest dose they could give without intolerable side effects, they scrambled to prepare slides with graphs and statistics to convince the Food and Drug Administration that the drug should be tested in a larger Phase 2 trial. The agency required a summary of any and all side effects — there had been only a few — and any deaths of patients on the study; thankfully, there had been none since the drug was reformulated. In a matter of days they needed to submit their findings for a prestigious meeting of clinical oncologists in June.
First, though, Dr. Flaherty, 39, needed to respond to a desperate phone message from a patient named Christopher Nelson. It came the day after Christmas.
"Dr. Flaherty," the message said, "I need to get onto your trial."
Hoping for a Match
The doctor had expected the call.
Mr. Nelson, 42, and his wife, Sharlene, had come to see him just before Thanksgiving. They were planning to travel to Bethesda, Md., so Mr. Nelson could enroll in a trial for a different melanoma drug. But the couple, from Jackson, N.J., had learned of Dr. Flaherty's trial, and wanted to cover all their bases.
He liked them: Sharlene, a real estate broker who peppered him with questions, and Chris, a furniture installer around his own age with a penchant for low-stakes poker and the Grateful Dead. Both were quick to make light of a grim situation.
"I've gained the 60 pounds he's lost from the cancer," Mrs. Nelson observed. "Stress eating."
They had met after high school, at Levitz, the furniture store where they both worked. Like Dr. Flaherty, they had two children.
"He was never sick a day in his life," Mrs. Nelson told Dr. Flaherty. "Never had a headache, never took a sick day. I mean, can't you give me the common cold first? It had to be cancer?"
The trial in Bethesda, run by the National Cancer Institute, involved coaxing immune cells to grow in a test tube in a procedure that worked for only a small fraction of patients, Dr. Flaherty knew.
But there would be no point in Mr. Nelson taking PLX4032 if his tumor did not carry the right mutation. For now, the doctor had a slot for only one more patient on the trial, and he and his collaborators had agreed it was almost unethical to give the drug to people without that mutation.
He wished, not for the first time, that he could snap his fingers and know the genetic profile of his patient's cancer cells. But getting a hospital that had operated on a patient months earlier to retrieve a tumor sample from storage could take days or weeks; the test for the gene mutation could take even longer. To speed the process, Mr. Nelson drove his tumor sample himself fromRobert Wood Johnson University Hospital in New Brunswick, N.J., where it had been removed from his lymph nodes, to the laboratory at the University of Pennsylvania.
Dr. Flaherty agreed that while they waited, Mr. Nelson should proceed with the trial in Bethesda, which first required the removal of his tumor-laden spleen. Either way, that needed to go.
Mrs. Nelson thought her husband had died when she saw the stricken look on the face of the surgeon after the operation. Normally 2 pounds, the spleen had weighed 10. Mr. Nelson's liver was so enlarged that maneuvering around it had been almost impossible. And then, on Dec. 23, Mr. Nelson learned that the doctors running the trial had been unable to grow his immune cells.
On the phone, Dr. Flaherty assured him he would let them know his genetic status as soon as he found out. "If it's positive," Dr. Flaherty told him, "the spot is yours."
