Q21. What is the effect or benefit of vitamins or minerals during or post radiotherapy treatment?
It is important to encourage patients to liaise with their pharmacist, oncologist and drug information centre to receive appropriate advice about taking vitamins, minerals and other complementary and alternative medicines during their treatment. This will ensure correct advice is given on potential interactions with what they plan to take and their treatment regimen. Further information can be found on the Natural Medicines Comprehensive Database.
There has been one level I neutral quality study which is a systematic review of whether antioxidants should be taken during chemotherapy and radiotherapy . Twelve RCT’s were indentified in radiotherapy patients, of which six were specifically head and neck cancer patients. Five RCT’s were identified in chemotherapy patients, of which one was specific to head and neck cancer. The antioxidants studied include: dietary sources (vitamin E, beta carotene, mixed antioxidants – including vitamin A, vitamin C, beta carotene, N-acetylcysteine) and non-dietary sources (pentoxifylline, melatonin, amifostine, ellagic acid, glutathione). The review concludes that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged due to the possibility of tumour protection and reduced survival.
For zinc there are four level II positive quality studies . All of these studies included patients receiving radiotherapy or chemoradiotherapy, except for the sub analysis of patients with nasopharyngeal tumours, who all received chemoradiotherapy . There is one level II neutral quality study  in patients receiving chemoradiotherapy, and one neutral quality study  which was in patients receiving radiotherapy alone.
Two positive quality studies with zinc supplements taken during chemoradiotherapy have reported on survival outcomes. One study  demonstrated a marginal non significant improvement of 3 year local disease free survival in patients, with a significant improvement for those with stage III or IV disease. One study  in advanced nasopharyngeal cancer patients showed a significant improvement of 5 year overall, local free and disease free survival. The other positive quality studies showed that zinc supplements had a delayed effect and reduced severity on development of dermatitis and mucositis , and a non significant delay in developing taste changes, with no impact on taste recovery post treatment . One study reported no effect on weight  whereas one study reported some benefit with the zinc . No effect on quality of life was noted . The neutral quality study  reported a sub group analysis of nasopharyngeal and oral cavity tumour patients that demonstrated benefits of zinc supplementation in improving mucositis in oral cavity tumour patients but not in nasopharyngeal tumour patients. Another neutral quality study had no effect on weight and more rapid improvement in taste . However there is some evidence that zinc supplements and or high dietary zinc intake can cause clinically significant interference with Cisplatin chemotherapy . It is also unclear whether zinc may alter the benefits of radiotherapy on the tumour.
There are five level II positive quality studies for vitamin E , two level II neutral quality studies , and one level III-2 negative quality paper . One study reported that vitamin E taken during treatment resulted in an increased rate of recurrence or second primary cancers, in subsequent analysis this risk was only found in smokers compared to non smokers who took the supplements. Another trial found cause-specific mortality rates were higher in the vitamin E group. While one study reported benefits of vitamin E and beta carotene for less severe side effects, this benefit was not sustained for vitamin E alone. There was no benefit on quality of life. Vitamin E as a mouthwash showed a reduction in mucositis and pain, but no effect on weight or survival. In another study vitamin E was found to increase salivary rate.
A single level II positive quality study examined supplementation of vitamin A post treatment (all other studies took the supplements during and post treatment) . This study found an increase in loco-regional recurrent disease.
There are two level II neutral quality studies reporting on beta carotene. The first demonstrates fewer adverse effects and a lower local rate of recurrence with high dietary beta carotene intake/higher plasma beta carotene levels . This study was part of the larger trial looking at Vitamin E in conjunction with beta carotene, and the beta carotene supplementation was discontinued during the trial due to ethical concerns after another study had shown increased adverse effects in lung cancer patients . A second neutral study reported reduced mucositis, but no effect on survival .
One level IV neutral quality prognosis study also confirms higher plasma carotenoid levels being associated with improved survival . This was also demonstrated in a further study by the same authors (level III-2 negative quality), whereby higher dietary intakes of carotenoids were associated with progression free survival . The study suggests achieving this through higher intakes of carotenoid rich fruit and vegetables, due to negative impacts seen with carotenoid supplements in other studies.
There has been one level II neutral quality study for selenium supplementation which showed improved immune function . There is one level II neutral quality study , which demonstrated that selenium supplementation had no effect on radiation induced toxicities such as dysphagia, loss of taste, dry mouth or stomatitis. There is one level IV negative quality study that recommended 500ug/day of selenium during treatment to maintain normal selenium status. It was deemed not to affect survival or disease control rates and therefore deemed safe to use.
There has been one level IV positive quality study  investigating vitamin D status (serum and dietary intakes at baseline) which found no impact on disease and mortality outcomes. In the absence of any additional studies to form a body of evidence, no recommendation can be made at this stage.
|Zinc at doses of 25mg tds taken during or post (chemo) radiotherapy may reduce side effects (mucositis, taste changes), however care needs to be taken in its use due to potential and unknown interactions with chemotherapy and radiotherapy.||C|
|Vitamin E, at high doses of 400IU/d, may be associated with reduced survival or recurrent disease.||A|
|Selenium supplementation of 200ug/d taken daily during treatment may improve immune function, but has not been shown to have any impact on clinical symptoms.||C|
|Antioxidants should not be taken during chemotherapy or radiotherapy due to possible tumour protection and reduced survival.||B|
|Beta carotene (30mg/d) may reduce side effects, however care needs to be taken in its use due to other demonstrated effects of reduced survival or recurrent disease in other cancer patients.||B|
|Vitamin A, at high doses of 200 000IU/week, has no benefits and may have an adverse effect on survival and disease outcomes.||B|
|Zinc at doses of 25mg tds taken during or post (chemo) radiotherapy has been linked with survival benefits in patients with nasopharyngeal cancer, however care needs to be taken in its use due to potential and unknown interactions with chemotherapy and radiotherapy.||C|
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