2011-04-21 10:40:10
Six months ago, John Murphy found out he had less than six months to live.
Undetected skin cancer had lodged in the 65-year-old retired lawyer’s hip, and the tumor was spreading cancer through his blood like dandelion fluff in the wind.
It was full-blown, stage IV melanoma. By the time Murphy saw his family doctor in October, the deadly slurry had planted tumors in both lungs. One was the size of a hockey puck.
“It was a death sentence,” Murphy said on a recent afternoon as he gasped for breath, his face gleaming with sweat.
Advanced melanoma is the worst kind of cancer. It spreads like kudzu to vital organs and has long resisted radiation, chemotherapy and every other treatment. Most patients die within nine painful months.
By November, Murphy, long been an avid hiker, was drained of energy, limping on two canes, short of breath and wincing from pain.
“I was not sure I would make it to see Christmas,” he said. “I started making up my bucket list.”
But as he told his story recently, Murphy wasn’t panting because he was fighting tumors in a hospital bed. He was panting because was hiking a steep, remote trail to one of his favorite mountain summits.
In the last three months, Murphy’s tumors have almost melted away. His pain is gone. And he is flush with renewed vigor.
“I feel incredible, like I have been given my life back and appreciate it for the first time,” he said as he trudged up the path.
Murphy has been granted what he calls a “secular miracle.” He is taking a new combination of experimental cancer drugs that leading cancer researchers describe as ground-breaking and revolutionary.
The treatment — a type of targeted drug therapy — involves no radiation, no surgery, no chemotherapy, and no harsh side effects. Patients take a few pills per day.
The pills are packed with carefully crafted molecules designed to block certain cancer cells’ ability to divide by disrupting their mutated DNA. When the cells can’t divide, they die, and tumors start to shrink within weeks.
“It’s like you are removing the gas from the car so it can’t run,” said Dr. Bruce Chabner, clinical director of the Massachusetts General Hospital Cancer Center and former director of cancer treatment at the National Cancer Institute. “In the past, we could only put roadblocks in its way, and it would always find a way around. … This is really game-changing.”
About 8,000 people die in the United States every year from melanoma. Murphy is one of about 200 patients nationwide participating in the clinical study of these new drugs.
The story of how the experimental drugs — called B-RAF inhibitors and MEK inhibitors — reached clinical trials stretches back almost 10 years and includes an estimated $1 billion in research. The story of how Murphy reached the trials stretches back even further.
A FAMILY CONNECTION
It starts in 1959 with Murphy’s older brother Martin.
“He is the real hero of my story,” said John Murphy. The family also includes well-known local developer Chuck Murphy.
Martin Murphy was always fascinated by medicine. In high school, he worked summers helping with autopsies at what is now St. Francis Health Center. During his junior and senior years, he would get up before dawn to take care of a gang of rats he was using to test if radioactive testosterone affected the creation of red blood cells.
“Marty was a sound sleeper but I wasn’t,” John Murphy said. “I can remember setting my alarm for four to get up so I could wake him up to take care of the rats.”
In 1959, the rat experiment won Martin Murphy first prize at the regional science fair, and then at the national science fair.
The front page of The Gazette from June 12, 1959 shows Martin Murphy being congratulated by President Dwight Eisenhower for his win.
“It was always about medicine for me, helping people,” Martin Murphy said when reached by phone recently at his home in North Carolina.
He earned a degree in experimental medicine from New York University and a handful of post doctorate degrees, all focused on cancer. Before long he was a leader in the field. He founded the Institute for Hipple Cancer Research Center in 1977 and cofounded the journal “Stem Cells” in 1981 before most people knew what a stem cell was. He also started the journal “The Oncologist.”
Today, he is respected and influential in the increasingly complex and intertwined worlds of drug developers and cancer researchers.
When John Murphy learned about the tumor in his hip, his brother was the first person he called. Martin was at a cancer congress in Italy when the phone rang at 2 a.m.
On the other end, his brother in Colorado Springs sounded drained of hope.
“John, cancer treatment today is not the same as it was when we were kids,” he said reassuringly. “It isn’t even the same as it was last year. Exciting things are happening.”
Martin Murphy started devising a strategy, plucked from his encyclopedic knowledge of the cancer world.
He got in touch with his close friend Bruce Chabner, who is also editor-in-chief of “The Oncologist.”
Chabner immediately brought up the experimental drug trial that had the potential for striking results.
If John Murphy had not had one of the leading cancer researchers as a brother, and had stayed in Colorado for treatment, he would likely have gotten chemotherapy, which might have extended his life a few months, but would have heaped on its own toxic side effects, including hair loss, nausea and fatigue.
“John Murphy was very lucky,” said Chabner, “Because Marty knew me and I knew about this very promising study.”
Within weeks, John Murphy was on his way to Boston.
But cancer patients should not think they can’t get the best care unless they have connections, Martin Murphy said. Any cancer patient can do what he did for his brother.
“They just need to be committed. They need to work to find the very best care.”
PROMISING RESULTS
By the time John Murphy joined the experimental drug study in December 2010, work on targeted gene inhibitors had already been progressing for a decade, but they were just starting to prove their worth.
In 2002, a group of British scientists studying cancer tumors noticed that among the thousands of genetic mutations in cells, one showed up over and over: a mutated gene called B-RAF.
“It’s one of the genes that drive cell growth,” said Dr. Donald Lawrence, Murphy’s oncologist at Mass General. “When B-RAF is mutated, it acts like a switch stuck in the ‘on’ position. Cells keep spitting and splitting out of control. What researchers began looking for is a molecule to get inside the cancer cell and shut the switch off.”
It was easier said than done. Trials of the first generation of B-RAF inhibitors started in 2004 but met with little success. The cancer continued to grow and the drugs interfered with some healthy cells as well, causing nasty side effects. All of the terminal melanoma patients taking the new drugs died.
In 2009, Lawrence began testing a more concentrated version of the drug made by the pharmaceutical giant GlaxoSmithKline, and saw something surprising. At first, tumors in terminal melanoma patients with the B-RAF mutation would melt away.
“It is almost miraculously effective,” he said. “We saw tumors shrink in 80 percent of patients in six months with very few side effects. These people get their life back.”
But within a year almost every patient relapsed and died.
In 2010, Lawrence and the other doctors leading the GlaxoSmithKline studytried something new. They theorized that when cancer cells found the B-RAF gene blocked, some started using a molecular back door known as MEK to continue to multiply.
So the researchers devised a new drug trial that would give patients the B-RAF inhibitor that had proved so effective in the short term, as well as a MEK inhibitor to block the back door.
That is the study Murphy joined a few months ago.
“It is really a new paradigm. For the first time science is starting to understand different cancers at a molecular level and devising individual treatments tailored to them,” Lawrence said.
But will it work? Or, with the metaphorical front and back doors blocked, will melanoma find a molecular window?
“That’s what we don’t know,” said Martin Murphy. “How durable is it? How long will it last?”
ALMOST BACK TO NORMAL
John Murphy started the drug trial on Dec. 27, 2010. Each day he takes five pills: Four vitamin-sized red ones for the B-RAF and one little white one for the MEK.
“I couldn’t believe that was it,” he said. “If this study works, people will be able to fight stage IV cancer by going to the pharmacy.”
Within weeks, he noticed his strength returning. He put away one cane. Then the other.
Then he was able to snowblow his driveway. By the end of January he was snowblowing his neighbors’ driveways.
He even felt strong enough to start hiking in the mountains with friends again.
He stated calling the pills “Smith and Wesson.” They were his secret weapon.
Feb. 24 he went in for a CT scan and found that all but the biggest of his tumors had disappeared and the remaining one — once the size of a hockey puck — was smaller than a pea. Another scan last week, showed it is now just a speck.
“I’m almost totally back to normal. I do 45 minutes on the StairMaster several times a week,” he said recently.
He knows he could relapse, but the drugs have already given him months of healthy living he never though he would have.
B-RAF inhibitors could be approved by the Food and Drug Administration for general use in the next year, said Chabner, the Massachusetts General Hospital Cancer Center clinical director.
They are not a cure for cancer, Martin Murphy said, just a treatment that patients have to continue indefinitely. And they do not work on all cancers, just those caused by a B-RAF mutation. But they are a major advance.
“I don’t know if there is any bigger deal,” Martin Murphy said. “Right now the expectations of these drugs is the most important thing happening in cancer medicine worldwide.”
His brother is just happy to have his life back.
“When you thought it was all lost and you suddenly get it back, everything changes,” John Murphy said. “I hug people a lot more now.”
—
Contact the writer: 636-0223
Members
BY NEIL OSTERWEIL
