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New Pancreatic Cancer Treatment Activates Immune System

In Early Study, Strategy Shrank Tumors in Some Patients

By Kathleen Doheny
WebMD Health News

Reviewed By Laura J. Martin, MD

March 24, 2011 -- A novel approach to pancreatic cancer treatment that activates the immune system works in some patients, according to a new study.

The treatment works by destroying the "scaffolding" around cancer cells, says researcher Robert H. Vonderheide, MD, DPhil, an associate professor of medicine in the division of hematology/oncology and the Abramson Family Cancer Research Institute, University of Pennsylvania.

"The therapy is an antibody," he says. ''Instead of binding to the cancer, this antibody binds to a molecule in the immune system, and that is CD40," he tells WebMD. Next, the immune system is activated, allowing it to attack the so-called scaffolding around the cancer cells. The scaffolding is destroyed and the tumor falls apart.

The process is somewhat like attacking a brick wall by dissolving the mortar in the wall, he says.

In the study, the new approach extended overall survival by nearly two months compared to conventional treatments. Progression-free survival, the length of time during which the tumor did not grow, was more than three months longer.

The results are encouraging, says William C. Phelps, PhD, director of preclinical and translational cancer research at the American Cancer Society, Atlanta. He reviewed the findings for WebMD.

"Pancreatic cancer is probably one of the most dismal of cancers, because there is very little effective treatment available and the course is rapid," Phelps tells WebMD.

The study findings are published in Science.

Pancreatic Cancer Treatment: Back Story

In 2010, about 43,140 people were diagnosed with pancreatic cancer, according to the American Cancer Society; 36,800 died.

Treatment is a challenge, Vonderheide says, because about 80% of people diagnosed have a tumor that is not operable.

For those patients, the standard treatment is chemotherapy with a drug known as gemcitabine (Gemzar). Another option, Vonderheide says, is to combine it with another drug, erlotinib (Tarceva).

But better options are needed, he says. "There is a huge need to find new approaches," he tells WebMD.

Pancreatic Cancer Treatment: Study Details

The researchers studied the new immune therapy for pancreatic cancer in mice and in people. In the human study, 21 patients with surgically incurable pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer, were given the combination of gemcitabine with the new antibody treatment, known as CP-870,893.

The antibody infusion, given once a month, was added to the routine gemcitabine treatment.

"They could keep receiving it until the tumor progressed or toxicity developed," Vonderheide tells WebMD.

The new treatment was found to be well tolerated in this phase 1 trial, Vonderheide says. Side effects included chills and fevers and usually went away within 24 hours.

After two cycles, the patients were scanned to evaluate the tumors. "We are reporting that five patients who received the antibody went on to tumor regression that was at least 30% or more," he says. That 30% is considered the cutoff for an acceptable response, he says.

To put the results in perspective, Vonderheide says that ''the response rate for gemcitabine alone is 5%, one out of 20. In a study this size [with the 21 patients] we would have expected one to have a response."

The median time for progression-free survival was 5.6 months (half longer, half less). The median overall survival time was 7.4 months.

In comparison, gemcitabine alone produces a median progression-free survival of 2.3 months and a median overall survival time of 5.7 months.

One surprise: the researchers thought the antibody treatment would activate white blood cells known as T cells to attack the tumor. But the treatment actually turned on another kind of white blood cells called macrophages.

The study was funded by the Abramson Family Cancer Research Institute, the National Cancer Institute and Pfizer Corp., which makes the antibody.

Pancreatic Cancer Treatment: Future and How It Works

Although the results are encouraging, Vonderheide says ''we have a lot of work to do.'' It will require several years of study and development before the approach is available, he says.

The concept reflects new understanding about cancer cells and what they need to thrive. "It's often thought that if you take out the tumor, 100% of what you take out is cancer cells, but that's not true," he tells WebMD. "A small part of the dense tumor is cancer; the rest of the material is this scaffolding, which the tumor uses to grow."

The tumors rely on this surrounding tissue for blood flow and for a defense against the immune system.

The antibody, he says, activates the immune system in other tissues outside the scaffolding, such as the lymph nodes and the spleen. These activated white blood cells then travel to the scaffolding around the tumor and destroy it.

''Without the scaffolding, the tumor cells don't survive as well," he says.

Pancreatic Cancer Treatment: Perspective

The effect of the treatment is small but important, Phelps says. "In pancreatic cancer, any effect is remarkable. The fact that he sees even in a small study some benefit is pretty remarkable."

The treatment approach reflects recent discoveries about how cancer grows, he says. "We've come to understand in the last three to five years that the somewhat normal cells that surround the tumor play an important role in allowing the tumor cell to grow. The environment of the tumor makes a difference."

SOURCES:

Robert H. Vonderheide, MD, DPhil, associate professor of medicine, division of hematology/oncology; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia.

William Phelps, PhD, director, Preclinical and Translational Cancer Research, American Cancer Society, Atlanta.

Beatty, G. Science, March 25, 2011: vol 331: pp 1612-1616.

© 2011 WebMD, LLC. All rights reserved.



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