USC/Norris oncologists test new front-line therapy for pancreatic cancer

USC/Norris Comprehensive Cancer Center oncologists are testing the effectiveness of a new drug against pancreatic cancer that targets the cancer from two directions.

In their National Cancer Institute-sponsored phase II clinical trial, researchers are evaluating how well BAY 43-9006 works alone and paired with gemcitabine, today’s standard chemotherapy for pancreatic cancer. Heinz-Josef Lenz, M.D., associate professor of medicine at the Keck School of Medicine of USC, is principal investigator on the trial, which ultimately aims to add much-needed options to medicine’s sparse arsenal against pancreatic cancer. Cancer of the pancreas causes about 27,000 deaths each year in the United States alone. “Pancreatic cancer is a major health problem, because we do not yet have highly effective ways to deal with it,” says Lenz, director of the gastrointestinal oncology program at USC/Norris. “The cancer is difficult to diagnose early, when it is most treatable, and can be aggressive. Because of the lack of effective systemic therapies, only 1 percent to 4 percent of patients will be alive five years after diagnosis.”

But Lenz hopes that targeted medications such as BAY43-9006 will become part of first-line treatment and help patients respond better to chemotherapies.

In this study, researchers will recruit 90 patients with metastatic pancreatic carcinoma. Half of the patients will take a BAY 43-9006 pill twice daily for four weeks, while the other half will both take the pills and receive weekly infusions of gemcitabine for three weeks at a time. Oncologists will evaluate how well tumors respond to the drugs, as well as monitor for side effects. Patients whose cancers progress when taking the new drug alone will be switched to the gemcitabine group.

Unlike traditional chemotherapies, which kill fast-growing cells (even some non-cancerous ones), targeted drugs such as BAY 43-9006 focus exclusively on a few targets specific to cancer cells. In this case, the compound aims to work in two ways: by directly inhibiting critical growth pathways of the cancer cells (even potentially killing the cells), while also attacking the blood vessels needed to nourish the tumor, Lenz says.

BAY 43-9006’s first strategy is to disrupt cell signaling in what scientists call the Ras gene pathway. The Ras oncogene drives cell division and is critical to many cancers’ development; moreover, mutations in the Ras gene occur in 90 percent of pancreatic cancers. By throwing a roadblock in the Ras signaling pathway, BAY 43-9006 attempts to keep cancer cells from proliferating. “This compound also has anti-angiogenic activity,” says Lenz. Angiogenesis is a process by which growing tumors recruit new blood vessels to keep them nourished. BAY 43-9006 is thought to inhibit angiogenesis by interfering with vascular endothelial growth factor (VEGF) receptors on blood vessel cells, as well as platelet-derived growth factor (PDGF) receptors, which are found on special cells that provide the external structure for blood vessels.

Encouraging results have already been reported from a phase II trial of the compound in renal cell carcinoma, or kidney cancer, and a phase I/II trial for the treatment of metastatic melanoma.