Health

Jun 30, 2011 5:55 PM by Dr. Anya Winslow

Doctors develop new arsenal in battle against cancer

As 65-year-old John Murphy strolls along one of Colorado's many scenic and well-hidden trails he reminisces ,"I got my diagnosis when the humming birds left and that was the last time I thought I'd see ‘em ."

With his well worn walking stick in hand and is faithful dog, Abby, at his side, he quickly strays off the relatively flat trail and scurries up a steep, rocky, slope. With only a slight pause between words he says, "This is kinda the terrain that I've always felt comfortable on." John looks and sounds healthy, but that was not the case around eight months ago.

In October of 2010, he was dealt a death sentence - stage IV melanoma. "The Denver oncologist told me it was going to take me," he says.

Melanoma spread rapidly from his hip to his lungs and infiltrated other areas of his body. One tumor was the size of a hockey puck.

Patients with stage IV melanoma have a very grim prognosis. Life expectancy is typically less than a year; however, treatments are evolving and are giving patients and their families hope.

One place that is making huge leaps in cancer research - both within the lab and in clinical trials - is Massachusetts General Hospital's Cancer Center in Boston. Upon his brother's urging, that is exactly where John and his wife, Mary, ventured to seek treatment, but they were not sure if the doctors in Boston could help.

"We are actually understanding that melanoma is not one disease, but many different diseases on a fundamental molecular level," says Dr. Donald Lawrence, Clinical Director of the center's Melanoma Program.

What Lawrence is talking about is a specific gene, BRAF, which all people have, but in certain individuals, like John, that sequence is mutated, and it drives the growth of the melanoma.

"BRAF is mutated in around fifty percent of cases," adds Lawrence. It is in those patients, who exhibit the ‘broken' gene, that they can help.

The drugs Lawrence and his team are using to treat patients with mutated BRAF target BRAF, strangling the cancer at its source. Additionally, as in John's case, they are using another drug that targets an enzyme called MEK, which is also critically involved in melanoma's growth.

In earlier trials, the team found that when they only used the BRAF inhibitor, it temporarily halted the growth of melanoma. With this combination therapy (BRAF plus MEK), they are hoping to have a longer lasting response.

Lawrence says with conviction, "It is almost a given now when we see a patient with melanoma that harbors a BRAF mutation, when we start them on a clinical trial with a BRAF inhibitor, that they are going to get better. Their tumor is going to shrink, patients who are symptomatic in pain, short of breath, feel better in a matter of days."

John started the treatment plan a few days after Christmas. Up until that point he softly says, "I ran out of strength several times and I borrowed [Mary's]...I thought I was gonna die. I thought the [Denver] doctor was absolutely right."

After only three days of being on the therapy, John started feeling better. "I'd say three days and Mary says the same thing. Mary says she saw me shrink right before her eyes and all of a sudden, I stated expanding again. By New Years Eve I stayed up until midnight, we went out and ate spaghetti [he laughs], and [before that] I couldn't eat anything," he says as his eyes grow wider.

As for the treatment itself, it is pretty simple. Patients have to fast an hour before and two hours after taking a few pills in the morning and a few pills at night. "So that's eighteen hours a day if I wanted to eat I could," says a laughing Murphy.

"These are pills. It's not intravenous therapy. It's not chemotherapy. There are side effects. The majority of patients are able to live their lives normally," adds Lawrence.

Side effects are modest, happen on occasion, and last a few days before passing. They include chills, rash, fever, joint pain, some inflammation, fatigue, and in rare instances effect the eyes.

John's episode of fever and chills occurred on the sixty first and sixty second day, and again last week. He says, "It feels like a really bad hangover, but I have all my money in my pocket and I remember everything."

"Ultimately, we hope that this will lead to a cure for advanced melanoma," says Lawrence. "We are not there yet, but we have a foot in the door and once you have that foot in the door, there's tremendous excitement about kicking that door open," he adds.

Lawrence's excitement is understandable. Their group's findings transcend melanoma cancer. "We've seen some early evidence that treating these other types of cancers that have [the] BRAF mutation, with these same drugs could lead to similar dramatic responses."

Lawrence says that 2% of lung cancers, 10% of colon cancers, some forms of thyroid and ovarian cancers have similar mutations that may potentially benefit from this therapy.

The success of this body of research is impressive and the forecast for cancer treatment is equally impressive. "I don't think there will ever be a random trial in melanoma again or [when] chemotherapy is the standard of care," Lawrence assertively adds.

John's turnaround from near death to back on the hiking trails was rapid. Equally impressive is the rate at which his tumors have been shrinking. After taking a look at John's lung CT scans prior to treatment and only after four months of treatment, his once 5 centimeter-sized tumor is barely visible. All the other marble-sized tumors in his body are also no longer visible.

"It's a tiny wisp of a thing now, while it started out as a golf ball," says Lawrence when he broke the news to John.

They could not have returned to Colorado Springs happier.

"Mary shook me early in the morning before sunrise that the humming birds were at the feeder," John says and he adds, "And she had tears in her eyes immediately and so did I."

 

* GlaxoSmithKline (GSK; Clinical trial number from government is NCT01072175) sponsors the trial.

** The drugs have yet to be named, but are referred to as the following: GSK2118436 targets the BRAF mutation; GSK1120212 targets MEK.

*** Click here to find out if you qualify to participate in the trial, as well as to determine if it is or will be offered in your area.


**** Click here for more information regarding the study.

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