Treating Pancreatic Cancer
Radiation-chemotherapy combination may hold a key

There is new hope on the horizon for patients with pancreatic cancer. Although it is only the fifth most common cancer (about 29,000 people get the disease each year), pancreas cancer has a disproportionate impact because it is one of the least curable illnesses. A novel treatment regimen being studied at the U-M, however, may provide significant improvement in outcomes for pancreatic cancer patients.

Mark Zalupski and Cornelius McGinn Photo: Martin Vloet

A team led by Cornelius McGinn, M.D., assistant professor of radiation oncology, and Mark Zalupski, M.D., associate professor of internal medicine in Medical Oncology, is testing a pancreatic cancer treatment that combines radiation and gemcitabine, a relatively new chemotherapy agent. Gemcitabine is a compound that resembles cytosine, one of the nucleoside building blocks of DNA. It functions by becoming incorporated into a cancer cell’s DNA, inhibiting further synthesis of the DNA and, in turn, hindering division of the cancer cells.

“We believe, in general, that concurrent radiation and chemotherapy are better than sequential use of the two modalities,” says Zalupski. “When chemotherapy is given with radiation therapy, it prevents the cell from repairing the damage caused by the radiation, which cancerous cells can often do, and the cell dies.” In this way, the compound functions as what is known as a “radiosensitizer.”

Zalupski and McGinn have taken a novel approach to the treatment. Other studies have tested the gemcitabine-radiation treatment using doses of gemcitabine lower than that used for chemotherapy alone, along with a standard, high dose of radiation administered by conventional means to a broad region in the upper abdomen.

“What we did was the flip side,” says McGinn. “Not only is gemcitabine a radiosensitizer, it’s an effective therapy when used alone. We provide patients a full dose of gemcitabine systemically and combine that with lower doses of radiation targeted more accurately.” In an initial phase I study begun in 1997, McGinn and Zalupski used the standard dose of gemcitabine and experimented with different levels of radiation that were all significantly lower than the conventional dose used in other studies. “A lower dose should be adequate to provide local control considering the radiosensitizing properties of the drug that were determined by our laboratory group,” McGinn adds.

In addition, the U-M team has incorporated a means of radiation therapy, developed by the Radiation Physics Division, called conformal radiation, which uses three-dimensional treatment planning to allow physicians to better pinpoint a tumor’s outer boundary and irradiate cancerous cells while sparing normal tissue. This is one of the factors that enable investigators to safely combine both modalities while providing potentially better treatment than with conventional radiation administration.

Chemotherapy and radiation are typically administered after surgical removal of the tumor. McGinn and Zalupski are also looking into preoperative gemcitabine-radiation therapy, which may make surgery more effective. “If we treat patients first, we might be able to improve the odds of removing the tumor. For some of our patients, even modest shrinkage of the tumor has been enough to allow the surgeon to remove it.”

McGinn and Zalupski’s team are in the process of conducting a phase II trial to further determine the treatment’s efficacy. While the phase I study focused on determining a tolerable combination of gemcitabine and radiation, a higher percentage of patients showed measurable tumor response than would have been anticipated by using either gemcitabine or radiation alone, and there was an apparent increase in average survival rate as well. “In my experience,” says Zalupski, “I haven’t seen patients do so well for so long.”

Arnold Morawa and Ted Lawrence Photo: Martin Vloet

Arnold Morawa, former assistant dean of the U-M School of Dentistry, is a personal supporter of the treatment protocol. Four years after surgery followed by the combination therapy, he shows no signs of relapse and continues his prominent Ann Arbor dental practice. “I really believe that this treatment and the way my body responded to it are the reasons I’ve done so well,” says Morawa.

Ted Lawrence, M.D., Ph.D., professor and chair of Radiation Oncology and Morawa’s physician, and Donna Schewach, Ph.D., professor of pharmacology, collaborated in laboratory studies to understand the basic mechanism of interaction between radiation and gemcitabine. This information was used by McGinn and Zalupski to design the clinical trials.

—RS

Department of Radiation Oncology

Information on gemcitabine as a pancreatic cancer treatment