BETHESDA, Maryland-Researchers have begun accruing 32,400 men for a long-term prostate cancer study that will test whether selenium and/or vitamin E can prevent the disease. The Southwest Oncology Group (SWOG) will coordinate the Selenium and Vitamin E Cancer Trial (SELECT) at more than 400 sites in the United States, Canada, and Puerto Rico. Participants will be followed for up to 12 years.
BETHESDA, MarylandResearchers have begun accruing 32,400 men for a long-term prostate cancer study that will test whether selenium and/or vitamin E can prevent the disease. The Southwest Oncology Group (SWOG) will coordinate the Selenium and Vitamin E Cancer Trial (SELECT) at more than 400 sites in the United States, Canada, and Puerto Rico. Participants will be followed for up to 12 years.
"SELECT is the first study designed to look specifically at the effects of vitamin E and selenium, both separately and together, in preventing prostate cancer," the National Cancer Institute (NCI) said in announcing the trial’s opening.
Selenium and vitamin E are antioxidants. The postulated mechanism for any protective benefit is the ability of antioxidants to neutralize free radicals and thus prevent genetic damage to cells that could lead to cancer.
Evidence that supplements of the two nutrients might help protect men against prostate cancer emerged from two prevention studies reported in the mid- and late 1990s. A study of selenium supplementation in 1,000 men and women found that it did not reduce nonmelanoma skin cancer. However, male participants had a reduction in incidence of prostate cancer of more than 60%.
Similarly, a Finnish study of 29,000 male smokers found that neither vitamin E nor beta-carotene reduced their risk of lung cancer, and, in fact, those taking beta-carotene were more apt to develop and die of the disease. However, the men who got vitamin E had a reduction in prostate cancer incidence of 32%.
"Because these trials were not designed with prostate cancer as their primary endpoint, the SELECT trial has been designed to answer the question definitively," said Charles Coltman, Jr., MD, director of the San Antonio Cancer Institute and chairman of SWOG.
Prostate cancer will strike some 198,100 American men during 2001 and cause 31,500 deaths. "These statistics give us a glimpse of the important impact prostate cancer prevention could have on the lives of men of all ages, but most critically black men, who are at the highest risk," Dr. Coltman said.
Incidence and mortality rates for prostate cancer are sharply increased in black men, compared with whites and others. "Their incidence rate is approximately 240 per 100,000, and the death rate is two to three times greater than that of Caucasians, particularly under the age of 70," said Isaac J. Powell, MD, associate professor of urology, Wayne State University.
Hispanics, Asians and Pacific Islanders, and American Indians and Alaskan Natives have incidence rates lower than whites.
"Prostate cancer strikes black men earlier and more often than it does white men, and it has a higher mortality rate in blacks than in whites. We are especially encouraging African-American men to enroll in this promising research," said Eric Klein, MD, head of Urologic Oncology at the Cleveland Clinic Foundation and clinical director of SELECT.
Dr. Powell said that the study committee is working with black organizations in an effort to encourage black mena group significantly underrepresented in most clinical trialsto enroll in the study. These groups include the National Medical Association, black urologists, church and social organizations, and fraternities and sororities. "Women play an important role in getting men to participate in studies," Dr. Powell said.
Thirty-eight Veterans Affairs medical centers will participate in the study. About 20% of the VA’s patient population is black.
SELECT is open to black men age 50 or older, and to men age 55 or older of other ethnic and racial groups. Men must be in generally good health and cannot have had any other cancer, except nonmelanoma skin cancer, in the last 5 years. There is no upper age limit for enrollment, but each site will judge whether it thinks a potential participant will remain compliant for the course of the study and is likely to be alive at its conclusion.
Investigators hope to complete enrollment in SELECT during its first 5 years. This would enable a minimum follow-up of 5 years for each man.
Study enrollees will be randomized to four groups, and participants in each will be asked to take two capsules a day. One group will receive 200 mg of selenium daily and placebo. A second arm will take 400 mg of vitamin E and placebo. The third group will get both selenium and vitamin E, and the fourth will take two placebo capsules.
Participants will have an initial screening interview and a brief physical examination at the time of enrollment, and general health screenings will be performed every 6 months while they are enrolled in the trial, Dr. Klein said.
In addition, monitoring for the development of prostate cancer will be performed in accordance with the standard of care at each study site. "Such screenings will help ensure early diagnosis and therapy for anyone who develops prostate cancer while enrolled in the trial," he said.
Men taking large doses of aspirin or other anticoagulants are ineligible for the study. Participants must also have normal blood pressure, either naturally or as the result of taking antihypertensives. The Finnish study of 29,000 smokers found an increased risk of cardiovascular and cerebrovascular events among men taking vitamin E who had uncontrolled high blood pressure. "We don’t anticipate a problem in SELECT because of the blood pressure criteria," Dr. Klein said.
Enrollees in the trial will not have to change their diets. However, they must stop taking any vitamin E or selenium supplements that they purchase themselves. SWOG will provide a specially formulated multivitamin free to participants, spouses, or significant others for the duration of the study, if they wish to take it. The multivitamin does not contain either vitamin E or selenium, and it will not interfere with the conduct of the trial, according to NCI.
The Institute is funding SELECT, which is expected to cost about $12 million a year over its 12-year course. Four pharmaceutical companies are providing the selenium and vitamin E capsules.