Vitamin D Tested for Preventing Lung Cancer in High-Risk Patients

NCI CAM Annual Report-FY10

At the Roswell Park Cancer Institute (RPCI) in Buffalo, New York, more than a decade’s worth of work devel­oping vitamin D-based approaches to cancer therapy has produced some possible options and hope for the millions of current and former smokers at high risk for lung cancer. “The burden of lung cancer is not shouldered exclusively by people who continue to smoke cigarettes,” explained Mary E. Reid, Ph.D., associate professor of oncology and Director of Collaborative Research at RPCI. “While 40-50 million Americans have stopped smoking, their risk of developing lung can­cer remains high for as many as 30 years after smoking cessation.” And there are still many people who have been unable to stop smoking, despite the known risks, she added.

This is where calcitriol (1,25-dihydroxychole­calciferol) – the primary active form of vitamin D – comes in. Normally, the body takes in vitamin D through foods like fish and milk, dietary supplements, and produces its own vitamin D with the aid of sunlight. Vitamin D exerts its effect on the body via the vitamin D receptor (VDR) which is found in the cells of many types of tissues, including the lungs and prostate gland. Calcitriol has shown promise in preventing lung, prostate, and other cancers, Dr. Reid explained. She was the senior author on a study* that was the first to demonstrate that VDR is expressed in many different types of human lung tissue, from normal cells through the spectrum of precancerous changes, to full-blown tumors.

With NCI funding**, RPCI will soon begin a Phase II clinical trial testing calcitriol as a preventive agent in people at high risk for lung cancer, Dr. Reid reported. But first, the U.S. Food and Drug Administration (FDA) has asked RPCI scientists to conduct a small pilot study on 40 current and former smokers between ages 40-80 from their High Risk Lung Cancer Cohort. It will determine the safety of the proposed dose of calcitriol they are planning to use for the larger Phase II prevention study.

The patients in the pilot study will receive 45 micrograms of calcitriol every other week for 3 months, Dr. Reid explained. A common daily dose of calcitriol for patients with low calcium levels is 0.25 micrograms per day. Clinicians have found at least some form of precancerous tissue in the lungs of these patients – all of whom suffer from chronic obstructive pulmonary disease (COPD) – by passing a bronchoscope through the mouth or nose into the lungs to examine and collect samples. Dosing toxicities (or side effects) in the pilot study are graded from 1 through 4, with grades 1 and 2 being less serious. The pilot study will not only look for any grade 3 or 4 toxicities in the calcitriol dose but will also report any other adverse effects to the FDA. Since 1999, RPCI researchers have conducted 6 clinical trials studying calcitriol and this dosage level has never produced any high-grade toxicities, and only a handful of low-grade toxicities, Dr. Reid said.

“I feel it’s important to be able to offer these high-risk patients some real options,” Dr. Reid commented. “They are fully aware that lung cancer can amount to a death sentence, and even so some are unable to quit smoking. Generally they are very happy to faithfully take a pill that reduces their risk, as long as there are no seri­ous side effects. We see so many people at the clinic with COPD and damage to their airways, usually from smoking or other environmental exposures.” The current standard of care in the United States is simply to screen such patients routinely to detect changes in their lung and airway tissue indicating early cancer. “Under­standably people want, and deserve more,” she said.

The Phase II trial that will follow the pilot safety study will provide calcitriol for 6 months to about half of the patients. The remaining patients, serving as a control group, will get a placebo for only the first 6 months and will then receive calcitriol for another 6 months, Dr. Reid said. “All study participants will be getting at least some of the treatment that we believe may be effective in preventing progres­sion of any disease they may be harboring,” she concluded.