"About 30 percent of men with locally advanced prostate cancer fail radiation therapy because the cancerous cells become resistant to treatment," said Constantinos Koumenis, Ph.D., lead researcher. "Any agent that increases the cancer cells' sensitivity to radiation, without significantly affecting normal cells, would be of great benefit."
Increasing radiation dose is not always a treatment option because it can affect urinary, bowel and sexual function. In laboratory studies, Wake Forest researchers found that Zemplar, a drug manufactured to mimic vitamin D hormone (the active form of vitamin D) worked in synergy with radiation therapy to kill cancer cells and prevent cancer cell multiplication, while having little effect on normal cells.
With the combination of Zemplar and external beam radiation therapy, researchers were able to lower the radiation dose by 2.4 times and get the same results as when radiation was the sole treatment.
"These results are very promising, but they must be duplicated in animal studies before being tested in humans," said Koumenis, an assistant professor of radiation oncology.
The Wake Forest study is the first to show that Zemplar can sensitize cancer cells to radiation treatment. Previous laboratory studies showed that the drug can reduce the proliferation, or growth, of tumor cells.
Zemplar is one of several drugs designed to mimic vitamin D hormone, and is approved by the U.S. Food and Drug Administration. It is used to treat high levels of parathyroid hormone and is being studied as a cancer treatment. Vitamin D hormone, also known as calcitriol, is not itself a viable treatment because in large doses it can lead to excess calcium in the blood and affect bone metabolism and structure.
"The fact that Zemplar is already approved means it could be used in treatment sooner," said Koumenis. "We've shown that the combination of Zemplar and radiation are synergistic in tumor cells, but much less so in normal cells. This means we could potentially increase the killing of the tumor cells, while minimizing the damage to normal cells."
The researchers tested the treatment in prostate cancer cells taken from recent patients, as well as in a collection of tumor cells, called a "cell line," that had been circulated among scientists for many years.
"Because cell lines have been studied for so many years, some scientists question whether they truly reflect the biology of prostate tumors," said Koumenis. "The ability of our collaborative team to isolate 'fresh' tumor cells from patients allowed us to look at both; and we found the same effects in both groups of cells."
The research was a collaborative effort between Koumenis; Scott Cramer, Ph.D., assistant professor of cancer biology; and Gary Schwartz, Ph.D., associate professor of cancer biology and scientific director of the Prostate Cancer Center of Excellence. The researchers have applied for funding to continue their research by studying the treatment in animals, where they hope to learn more about the optimum dose and timing of the combination therapy.
In the study, the researchers also compared Zemplar with vitamin D hormone, or calcitriol. Zemplar is designed to mimic the effects of calcitriol, without its side effects. The researchers found the Zemplar was just as effective as calcitriol when used in combination with radiation therapy.
Prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death in men in the United States.
Small amounts of vitamin D are present in foods such as tuna, salmon and vitamin-fortified milk, although most vitamin D is made in the body after casual exposure to sunlight. The vitamin exists in several forms, some of which are inactive. The liver and kidneys help convert vitamin D to its active form, calcitriol, also known as vitamin D hormone. Its role is to increase calcium absorption from the intestine and promote normal bone formation.