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Trial Tests Chemo-Immunotherapy with Pancreatic Cancer

Chemotherapy (National Institutes of Health)

(National Institutes of Health)

An early-stage clinical trial found a combination of chemotherapy and antibody protein caused some patients with pancreatic cancer to shrink their tumors. The findings of a study by researchers at University of Pennsylvania in Philadelphia and University of Washington in Seattle appear online in the journal Clinical Cancer Research (paid subscription required).

Cancer of the pancreas is a leading cause of cancer death. It usually spreads quickly and seldom is detected early, often because symptoms do not appear until the cancer is well advanced.

The team led by first author Gregory Beatty, a oncology and hematology professor in Penn’s medical school, combined the chemotherapy drug gemcitabine with the antibody protein CP-870,893, to find a safe dosage and test its anti-tumor activity in patients with advanced pancreatic cancer. Gemcitabine is an anti-metabolite, a drug that stops the genetic activity of cancer cells and thus their growth. The drug is marketed as Gemzar by Eli Lilly & Co.

CP-870,893 is an agonist antibody that binds to receptor cells and triggers an immune response. In this case, CP-870,893 binds with the CD40 receptor molecule on the surface of macrophages, white blood cells important to the immune system. After binding, the antibody triggers an immune response that attacks the stroma, fibrous tissue protecting tumors, thus making the tumors more vulnerable to gemcitabine.

In the study, 21 patients with advanced pancreatic cancer received weekly dosages of gemcitabine for three weeks with infusions of CP-870,893 every day for 28 days. Of the 21 patients, five reported a decrease in tumor size of at least 30 percent.

The most common adverse reaction to the treatments was cytokine release syndrome, a condition associated with monocolonal antibodies, causing chills and shaking. One patient with a history of vascular disease suffered a stroke after the start of treatments.

The trial employed an innovative imaging technique to observe and measure treatment responses. The technique, known as PET/CT FDG scanning, uses a radioactive glucose tracer to track the metabolism of glucose in a tumor. In this study, the PET/CT FDG allowed researchers to quantify glucose metabolism in individual tumors, providing a much more detailed and progressive account of the treatments.

“We incorporated imaging as early as two weeks after the first dose of treatment,” says Beatty in a university statement, “and we’re able to see changes and responses in terms of glucose metabolism even at this early time point in treatment, which predicted how well patients would respond two months later.”

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