Providence cancer research: One-two punch offers great hope for metastatic melanoma in clinical trials patients

June 06, 2012
Research at Providence Cancer Center shows a novel combination treatment could offer new hope for patients with advanced melanoma.

In a study of 12 clinical trial patients with metastatic melanoma, Providence Cancer Center researchers took a unique approach attacking the aggressive and deadly disease on two fronts: radiation and an immunotherapy treatment.
High-dose stereotactic body radiotherapy

Marka Crittenden, M.D., Ph.D., Brendan Curti, M.D., and Steven Seung, M.D., Ph.D., all part of the Earle A. Chiles Research Institute at Providence Cancer Center, developed a clinical research trial using high-dose stereotactic body radiotherapy, or SBRT, with an immunotherapy treatment called interleukin 2, or IL-2. View the video to see how the process works.

Steven Seung, M.D., Ph.D., Brendan Curti, M.D., and Marka Crittenden, M.D., Ph.D., all part of the Earle A. Chiles Research Institute at Providence Cancer Center, developed a clinical research trial using high-dose stereotactic body radiotherapy, or SBRT, with an immunotherapy treatment called interleukin 2, or IL-2. Although this specific combination therapy had never been tried, they believed it held great promise.

It did. The study suggests a response rate of 60 to 70 percent.

Their research results were published in the journal “Science Translational Medicine” on June 6 in a paper titled “Phase 1 Study of Stereotactic Body Radiotherapy and Interleukin-2: Tumor and Immunological Responses.”

“We are looking to understand why this worked so well,” said Dr. Curti, director, genitourinary oncology research and biotherapy clinical program, Providence Cancer Center. “It appears that memory immune cells are significantly boosted by the combination of SBRT radiation and IL-2.”

It is already known that the immune system has the ability to attack cancer cells, the main way being with an immune cell called a T-cell. T-cells can recognize what is foreign in the body and eliminate it. They do this by looking for proteins that don’t belong in the body. However, cancers can hide from T-cells in many ways, including concealing the proteins that the T-cells would use to recognize a form of cancer.

Providence researchers pursued the idea of using a high dose of focused radiation on a tumor to break open some of the cancer cells in the tumor, helping to release proteins the T-cells would recognize. For the T-cells to really thrive, the ones that recognized the cancer proteins need another signal to divide and conquer. One of the strongest signals to make the T-cells divide is interleukin-2 treatment. As these T-cells rev up and attack the melanoma, they also become memory cells – powerful tools in future cancer battles.

“The power of this combination of radiation and interleukin-2 is a remarkable thing,” said Dr. Curti. Tumors in some clinical trial patients completely disappeared during the six months of treatment.

A second clinical trial involving 40 patients now is under way.  

“If our preliminary work is confirmed, many more patients with advanced melanoma could find great hope in this combination therapy – their cancer could be placed in remission,” said Dr. Curti. “In addition, if this therapy continues to show promise we could apply it to other immune-based cancer treatments for renal, breast and prostate cancers.”

Providence installed the high-dose stereotactic body radiotherapy machine that allowed for this novel approach at the time the new cancer center opened in 2008. “Imagine taking a magnifying glass and focusing sunlight to burn your name on a piece of wood,” said Dr. Seung, director, The Gamma Knife Center of Oregon at Providence Cancer Center, and a radiation oncologist with The Oregon Clinic., “That’s exactly how this machine works.”

In addition, Providence treats a high volume of patients with melanoma, many undergo IL-2 therapy. It seemed natural to combine the two. Researchers knew the combination had been tried about two decades ago, but with a very different radiation technique and lower dose of IL-2. The early work was not effective.

“We built on that idea,” said Dr. Curti. “Radiation carefully applied has important effects on the immune system and these can be amplified by IL-2 immunotherapy. This appears to be the reason we had better clinical outcomes.”

“That’s the beauty of this study,” said Dr. Seung. “We didn’t create anything new, but the approach was novel at how we combined the two.”

“What’s particularly great about Providence is that we have a lot of support from the community which means that these studies can get into patients faster,” said Dr. Crittenden, director, translational radiation research, Providence Cancer Center, and a radiation oncologist with The Oregon Clinic. “The work that is done in the lab can be quickly translated into patients because of the support for these clinical studies.”

There are 80,000 new cases of melanoma diagnosed each year in the United States. It is potentially curable if caught in the early stages. When it spreads to other organs, the survival rate is 5 percent or less.

“Although there have been some advances recently, these new medicines have the potential to slow down melanoma but rarely, if ever, cure it,” says Dr. Curti. “So our goal, of course, is to find treatments that work not just at a high rate, but also for the long term.”

Journalists:

The following video clips and news release are available for download and use in your stories.