Q21. What is the effect or benefit of vitamins or minerals during or post radiotherapy treatment?

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Q21. What is the effect or benefit of vitamins or minerals during or post radiotherapy treatment?

Summary

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.

Antioxidants

There has been one level I neutral quality study which is a systematic review of whether antioxidants should be taken during chemotherapy and radiotherapy [1]. 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.

Zinc

For zinc there are four level II positive quality studies [2][3][4][5]. All of these studies included patients receiving radiotherapy or chemoradiotherapy, except for the sub analysis of patients with nasopharyngeal tumours, who all received chemoradiotherapy [2]. There is one level II neutral quality study [6] in patients receiving chemoradiotherapy, and one neutral quality study [7] which was in patients receiving radiotherapy alone.

Two positive quality studies with zinc supplements taken during chemoradiotherapy have reported on survival outcomes. One study [3] 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 [2] 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 [5], and a non significant delay in developing taste changes, with no impact on taste recovery post treatment [4]. One study reported no effect on weight [5] whereas one study reported some benefit with the zinc [4]. No effect on quality of life was noted [4]. The neutral quality study [6] 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 [7]. However there is some evidence that zinc supplements and or high dietary zinc intake can cause clinically significant interference with Cisplatin chemotherapy [8]. It is also unclear whether zinc may alter the benefits of radiotherapy on the tumour.

Vitamin E

There are five level II positive quality studies for vitamin E [9][10][11][12][13], two level II neutral quality studies [14][15], and one level III-2 negative quality paper [16]. 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.

Vitamin A

A single level II positive quality study examined supplementation of vitamin A post treatment (all other studies took the supplements during and post treatment) [17]. This study found an increase in loco-regional recurrent disease.

Carotenoids

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 [15]. 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 [18]. A second neutral study reported reduced mucositis, but no effect on survival [19].

One level IV neutral quality prognosis study also confirms higher plasma carotenoid levels being associated with improved survival [20]. 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 [21]. 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.

Selenium

There has been one level II neutral quality study for selenium supplementation which showed improved immune function [22]. There is one level II neutral quality study [23], 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[24]. It was deemed not to affect survival or disease control rates and therefore deemed safe to use.

Vitamin D

There has been one level IV positive quality study [25] 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.

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Recommendation Grade
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
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

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References

  1. Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst 2008 Jun 4;100(11):773-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18505970.
  2. 2.0 2.1 2.2 Lin YS, Lin LC, Lin SW. Effects of zinc supplementation on the survival of patients who received concomitant chemotherapy and radiotherapy for advanced nasopharyngeal carcinoma: follow-up of a double-blind randomized study with subgroup analysis. Laryngoscope 2009 Jul;119(7):1348-52 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19402154.
  3. 3.0 3.1 Lin LC, Que J, Lin KL, Leung HW, Lu CL, Chang CH. Effects of zinc supplementation on clinical outcomes in patients receiving radiotherapy for head and neck cancers: a double-blinded randomized study. Int J Radiat Oncol Biol Phys 2008 Feb 1;70(2):368-73 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17980503.
  4. 4.0 4.1 4.2 4.3 Halyard MY, Jatoi A, Sloan JA, Bearden JD 3rd, Vora SA, Atherton PJ, et al. Does zinc sulfate prevent therapy-induced taste alterations in head and neck cancer patients? Results of phase III double-blind, placebo-controlled trial from the North Central Cancer Treatment Group (N01C4). Int J Radiat Oncol Biol Phys 2007 Apr 1;67(5):1318-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17394940.
  5. 5.0 5.1 5.2 Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomized study. Int J Radiat Oncol Biol Phys 2006 Jul 1;65(3):745-50 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16751063.
  6. 6.0 6.1 Lin YS, Lin LC, Lin SW, Chang CP. Discrepancy of the effects of zinc supplementation on the prevention of radiotherapy-induced mucositis between patients with nasopharyngeal carcinoma and those with oral cancers: subgroup analysis of a double-blind, randomized study. Nutr Cancer 2010;62(5):682-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20574929.
  7. 7.0 7.1 Silverman JE, Weber CW, Silverman S Jr, Coulthard SL, Manning MR. Zinc supplementation and taste in head and neck cancer patients undergoing radiation therapy. J Oral Med 1983;38(1):14-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/6573453.
  8. Natural Medicines Comprehensive Database. Natural Medicines Comprehensive Database (Online). Stockton: Therapeutic Research Faculty. 2017 Nov 20;(Accessed 13/1/2011) Abstract available at http://www.naturaldatabase.com.
  9. Meyer F, Bairati I, Fortin A, Gélinas M, Nabid A, Brochet F, et al. Interaction between antioxidant vitamin supplementation and cigarette smoking during radiation therapy in relation to long-term effects on recurrence and mortality: a randomized trial among head and neck cancer patients. Int J Cancer 2008 Apr 1;122(7):1679-83 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18059031.
  10. Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, et al. Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol 2005 Aug 20;23(24):5805-13 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16027437.
  11. Bairati I, Meyer F, Gélinas M, Fortin A, Nabid A, Brochet F, et al. A randomized trial of antioxidant vitamins to prevent second primary cancers in head and neck cancer patients. J Natl Cancer Inst 2005 Apr 6;97(7):481-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15812073.
  12. Ferreira PR, Fleck JF, Diehl A, Barletta D, Braga-Filho A, Barletta A, et al. Protective effect of alpha-tocopherol in head and neck cancer radiation-induced mucositis: a double-blind randomized trial. Head Neck 2004 Apr;26(4):313-21 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15054734.
  13. Bairati I, Meyer F, Jobin E, Gélinas M, Fortin A, Nabid A, et al. Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients. Int J Cancer 2006 Nov 1;119(9):2221-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16841333.
  14. Chitra S, Shyamala Devi CS. Effects of radiation and alpha-tocopherol on saliva flow rate, amylase activity, total protein and electrolyte levels in oral cavity cancer. Indian J Dent Res 2008;19(3):213-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18797097.
  15. 15.0 15.1 Meyer F, Bairati I, Jobin E, Gélinas M, Fortin A, Nabid A, et al. Acute adverse effects of radiation therapy and local recurrence in relation to dietary and plasma beta carotene and alpha tocopherol in head and neck cancer patients. Nutr Cancer 2007;59(1):29-35 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17927499.
  16. Chitra S, Shyamaladevi CS. Modulatory action of α-tocopherol on erythrocyte membrane adenosine triphosphatase against radiation damage in oral cancer. J Membr Biol 2011 Mar;240(2):83-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21327633.
  17. Jyothirmayi R, Ramadas K, Varghese C, Jacob R, Nair MK, Sankaranarayanan R. Efficacy of vitamin A in the prevention of loco-regional recurrence and second primaries in head and neck cancer. Eur J Cancer B Oral Oncol 1996 Nov;32B(6):373-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9039219.
  18. Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst 1996 Nov 6;88(21):1550-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8901853.
  19. Mills EE. The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis. Br J Cancer 1988 Apr;57(4):416-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3390377.
  20. Sakhi AK, Russnes KM, Thoresen M, Bastani NE, Karlsen A, Smeland S, et al. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study. BMC Cancer 2009 Dec 21;9:458 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20025747.
  21. Sakhi AK, Bøhn SK, Smeland S, Thoresen M, Smedshaug GB, Tausjø J, et al. Postradiotherapy plasma lutein, alpha-carotene, and beta-carotene are positively associated with survival in patients with head and neck squamous cell carcinoma. Nutr Cancer 2010;62(3):322-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20358469.
  22. Kiremidjian-Schumacher L, Roy M, Glickman R, Schneider K, Rothstein S, Cooper J, et al. Selenium and immunocompetence in patients with head and neck cancer. Biol Trace Elem Res 2000 Feb;73(2):97-111 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11049203.
  23. Büntzel J, Riesenbeck D, Glatzel M, Berndt-Skorka R, Riedel T, Mücke R, et al. Limited effects of selenium substitution in the prevention of radiation-associated toxicities. results of a randomized study in head and neck cancer patients. Anticancer Res 2010 May;30(5):1829-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20592387.
  24. Buntzel J, Micke O, Kisters K, et al. Selenium substitution during radiotherapy of solid tumors. Trace Elements and Electrolytes 2011;28:101-4.
  25. Meyer F, Liu G, Douville P, Samson E, Xu W, Adjei A, et al. Dietary vitamin D intake and serum 25-hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients. Int J Cancer 2011 Apr 1;128(7):1741-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20533282.

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