Vitamin D hormone mimic boosts radiation results

A drug designed to mimic the effects of vitamin D hormone may be able to boost the effectiveness of radiation treatment for prostate cancer, report researchers in the current on-line edition of the British Journal of Cancer​​.

Prostate cancer is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death in men in the United States.

"About 30 per cent of men with locally advanced prostate cancer fail radiation therapy because the cancerous cells become resistant to treatment,"​ said lead researcher Constantinos Koumenis. "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, researchers from Wake Forest University Baptist Medical Center 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 the drug and external beam radiation therapy, researchers said they were able to lower the radiation dose by 2.4 times and get the same results as when radiation was the sole treatment.

Zemplar is one of several drugs designed to mimic vitamin D hormone, and is approved by the US 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.

Existing in several forms - some of which are inactive - 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 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.

The Wake Forest study is the first to show that Zemplar can sensitise cancer cells to radiation treatment. Previous laboratory studies showed that the drug can reduce the proliferation, or growth, of tumour cells.

"The fact that it 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 tumour cells, but much less so in normal cells. This means we could potentially increase the killing of the tumour cells, while minimising 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 tumour cells, called a 'cell line', that had been circulated among scientists for many years.

In the study, the researchers also compared Zemplar with vitamin D hormone, or calcitriol. Although Zemplar is designed to mimic the effects of calcitriol, it does not produce its side effects. The researchers found the Zemplar was just as effective as calcitriol when used in combination with radiation therapy.

The researchers say they 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.