Vitamin E Does Not Help Head and Neck Cancer PatientsKey Words
Head and neck cancer; antioxidants; vitamin E; beta-carotene. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
A large randomized study of patients treated with radiation therapy for head and neck cancer found that vitamin E supplements did not prevent the occurrence of second primary tumors and may be associated with an increased risk of cancer recurrence. The results demonstrate that vitamin E supplements are not beneficial to patients with stage I or II head and neck cancer.
Sources
Journal of the National Cancer Institute, April 6, 2005
Journal of Clinical Oncology, August 20, 2005.
Background
Antioxidants are substances that may protect cells from the damage caused by unstable molecules known as free radicals. Free radical damage may lead to cancer. Examples of antioxidants include beta-carotene, lycopene, and vitamins C, E, and A.
A large amount of data on both alpha-tocopherol (vitamin E) and beta-carotene suggests that these two antioxidants could be effective chemoprevention agents. That is, in test tubes and animals, these antioxidants slow or prevent cancer cells from growing. However, results from clinical trials have not been so clear. (See the National Cancer Institute factsheet, Antioxidants and Cancer Prevention: Questions and Answers.)
There are also limited data suggesting that antioxidants may protect normal tissues from radiation damage, though whether this means that cancer cells also escape remains a question of real concern.
Patients with head and neck cancers are commonly treated with radiation. Those with stage I or II cancers are at increased risk for developing a new independent cancer that is not associated with the first cancer, often referred to as a second primary cancer. Thus, it is important to determine whether interventions such as supplementation with antioxidants could reduce the risk of second primary cancers in this population while also protecting them against radiation’s side effects.
The Study
Between 1994 and 2000, Canadian researchers at five radiation therapy centers in Quebec enrolled 540 patients with stage I or stage II head and neck cancer. The patients were randomly assigned to take either pills containing vitamin E (400 IU) and beta-carotene (30 mg) or dummy pills (placebo) every day, starting on the first day of radiation therapy and continuing for three years after therapy’s end. The trial was double-blinded, meaning that neither the patients or the research teams knew which pill the patients were taking.
In 1996, researchers with the trial stopped the use of beta-carotene because of evidence from other trials that this particular antioxidant may increase the risk of lung cancer (see Beta-Carotene Supplements Confirmed as Harmful to Those at Risk for Lung Cancer). However, supplementation with vitamin E continued.
All patients were followed for a total of eight years. At the end of the trial, the results were analyzed in two ways. One way included all the patients; the other way excluded data from the first 156 patients enrolled in the trial before beta-carotene was stopped. The statistically strongest results concerned vitamin E alone.
The trial’s researchers had two main objectives. The first objective was to find out whether extended use of antioxidants could prevent the occurrence of second primary cancers in this group of patients. The second objective was to determine whether antioxidant supplementation during radiation therapy could decrease the side effects without decreasing the therapy’s ability to kill cancer cells. Results from each of the two objectives were published separately in different medical journals and were accompanied by editorials.
The trial was led by Isabelle Bairati, M.D., of Laval University Cancer Research Center in Quebec City.
Results
Objective 1 Results (Journal of the National Cancer Institute, April 6, 2005; see the journal abstract)
Antioxidants failed to prevent the development of second primary cancers among the patients. In fact, during the three-year period after radiation when patients continued taking their pills, those on vitamins had a somewhat higher rate of second primary cancers (mostly lung and trachea) than patients in the placebo group. Their risk of developing a second primary cancer was more than double (2.42 times higher) that of the placebo group. The risk was highest (2.88 time higher) for those taking vitamin E only.
Once they stopped taking the antioxidant, however, the vitamin group’s rate of second primary cancers became lower than that of patients taking the placebo. After eight years of follow-up, the rate of second cancers in both groups was about the same. Smokers were no more likely than non-smokers to get a second primary cancer during the course of the trial.
Recurrence rates followed a similar pattern. That is, patients taking an antioxidant were 1.65 times more likely to suffer a return of their original cancer during the three years they were on the supplement. The risk was highest among those taking only vitamin E (1.86 times higher). Five years after they stopped taking the supplement, their recurrence risk had fallen to the same level as those in the placebo group. Although suggestive of harm, these results were not statistically significant.
Objective 2 Results (Journal of Clinical Oncology, August 20, 2005; published online July 18, 2005; see the journal abstract)
Researchers assessed the damage to normal tissues and also asked patients about their quality of life at three points during the trial: while they were receiving radiation treatment, at the completion of treatment, and one month after treatment. During radiation treatment, 22 percent of all patients in the trial suffered some sort of severe (grade 3 or 4) side effects, such as a painfully dry mouth or sore throat. One month after radiation therapy, that proportion had dropped to 2 percent.
Those taking a combination of vitamin E and beta-carotene tended to suffer side-effects that were less severe. Those taking vitamin E only or placebo received no protection. Additionally, patients in the supplement group reported the same quality of life as those on placebo.
Researchers were concerned to find that the rate of local recurrence (that is, a return of the original cancer) was 54 percent higher among patients on the combination pill than those on placebo. There was a smaller but still worrisome increase among those on vitamin E only.
The researchers concluded that supplementation with vitamin E and beta-carotene (but not vitamin E only) during radiation therapy could reduce the severity of radiation therapy side effects. However, the protection may interfere with the ability of radiation to kill cancer cells.
Limitations
Patients with early-stage head and neck cancer are already had a higher-than-usual risk of developing second primary tumors, compared to patients with other kinds of cancer. The association between antioxidants and second primary tumors found in this trial might not be as strong among other cancer patients, said the authors.
Comments
“This is a large, well-done study with good compliance from the participants,” said Eva Szabo, M.D., of the National Cancer Institute’s Division of Cancer Prevention. “The results demonstrate that the use of vitamin E supplementation is not beneficial to patients with stage I or II head and neck cancer, either as a chemoprevention agent or to enhance quality of life during radiation therapy.”
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