Document Type : Original Article


1 Radiation Oncology Department, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Breast Diseases Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Colorectal Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


Background: Glioblastoma is the most prevalent and aggressive adult glial tumor. Patients who receive standard treatment have a mean survival of 12-14 months. Zinc is a micronutrient that has shown to have anticancerous effects. In the in vitro studies zinc had antineoplastic effects on gliobalstoma cells.
Method: This is a phase II randomized trial in which 60 patients in two groups were evaluated. The zinc group (29 patients) received zinc sulfate supplement 50 mg orally twice a day and the control group (31 patients) who were selected from historical case sreceived no supplements.
Results: Mean overall survival in the case and control groups were 9.93 (± 3.29) and 9.0 (± 3.56) months. In the case and control groups, the mean disease-free survival were 9.62 (SD ± 3.37) and 8.26 (SD ± 3.47) months. These differences were not statistically significant. Although overall survival and recurrence-free survival in patients in the case group was higher than the control group, there was no statistically significant difference (P = 0.485).
Conclusion: Zinc consumption was associated with better survival, but these differences were not statistically significant, necessitating further studies.


How to cite this article:

Ahmadloo N, Kameli P, Ansari M, Mosalaei A, Omidvari S, Nasrollahi H, et al. Effect of zinc sulfate on overall survival and progression-free survival in patients with glioblastoma multiforme, a phase II study. Middle East J Cancer. 2023;14(1):113-8. doi:10. 30476/mejc.2021.90568.1583.

  1. Farrell CJ, Plotkin SR. Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel- Lindau, and other syndromes. Neurol Clin. 2007;25(4):925-46, viii. doi: 10.1016/j.ncl.2007.07.008.
  2. Chi AS, Wen PY. Inhibiting kinases in malignant gliomas. Expert Opin Ther Targets. 2007;11(4):473- 96. doi: 10.1517/14728222.11.4.473.
  3. Duda DG, Jain RK, Willett CG. Antiangiogenics: the potential role of integrating this novel treatment modality with chemoradiation for solid cancers. J Clin Oncol. 2007;25(26):4033-42. doi: 10.1200/JCO. 2007.11.3985.
  4. Sneed PK, Prados MD, McDermott MW, Larson DA, Malec MK, Lamborn KR, et al. Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost. Neurosurgery. 1995;36(5):898-903; discussion 903- 4. doi: 10.1227/00006123-199505000-00002.
  5. Sanai N, Berger MS. Glioma extent of resection and its impact on patient outcome. Neurosurgery. 2008;62(4):753-64; discussion 264-6. doi: 10.1227/
  6. Gurpinar E, Vousden KH. Hitting cancers' weak spots: vulnerabilities imposed by p53 mutation. Trends Cell Biol. 2015;25(8):486-95. doi: 10.1016/j.tcb.2015. 04.001.
  7. Vousden KH, Lu X. Live or let die: the cell's response to p53. Nat Rev Cancer. 2002;2(8):594-604. doi: 10.1038/nrc864.
  8. Brat DJ, Prayson RA, Ryken TC, Olson JJ. Diagnosis of malignant glioma: role of neuropathology. J Neurooncol. 2008;89(3):287-311. doi: 10.1007/s11060- 008-9618-1.
  9. Fong LY, Nguyen VT, Pegg AE, Magee PN. Alphadifluoromethylornithine induction of apoptosis: a mechanism which reverses pre-established cell proliferation and cancer initiation in esophageal carcinogenesis in zinc-deficient rats. Cancer Epidemiol Biomarkers Prev. 2001;10(3):191-9.
  10. Pedersen PH, Rucklidge GJ, Mørk SJ, Terzis AJ, Engebraaten O, Lund-Johansen M, et al. Leptomeningeal tissue: a barrier against brain tumor cell invasion. J Natl Cancer Inst. 1994;86(21):1593- 9. doi: 10.1093/jnci/86.21.1593.
  11. Maita K, Hirano M, Mitsumori K, Takahashi K, Shirasu Y. Subacute toxicity studies with zinc sulfate in mice and rats. J Pest Sci. 1981;6:327-36.
  12. Brown MA, Thom JV, Orth GL, Cova P, Juarez J. Food poisoning involving zinc contamination. Arch Environ Health. 1964;8:657-60. doi: 10.1080/ 00039896.1964.10663736.
  13. Hambidge KM, Krebs NF, Miller L. Evaluation of zinc metabolism with use of stable-isotope techniques: implications for the assessment of zinc status. Am J Clin Nutr. 1998;68(2 Suppl):410S-413S. doi: 10.1093/ajcn/68.2.410S.
  14. Wuehler SE, Peerson JM, Brown KH. Use of national food balance data to estimate the adequacy of zinc in national food supplies: methodology and regional estimates. Public Health Nutr. 2005;8(7):812-9. doi: 10.1079/phn2005724.
  15. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987-96. doi: 10.1056/NEJMoa043330.
  16. Grabrucker AM, Rowan M, Garner CC. Brain-delivery of zinc-ions as potential treatment for neurological diseases: Mini review. Drug Deliv Lett. 2011;1(1):13- 23. doi: 10.2174/2210303111101010013.
  17. Ho E. Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem. 2004;15(10):572-8. doi: 10.1016/j.jnutbio.2004.07.005.
  18. Franklin RB, Costello LC. Zinc as an anti-tumor agent in prostate cancer and in other cancers. Arch Biochem Biophys. 2007;463(2):211-7. doi: 10.1016/ 2007.02.033.
  19. Timar J, Raso E, Paku S, Kopper L. Oral administration of a trace element preparation and zinc inhibit liver metastasis of 3LL-HH murine tumor cells. Int J Mol Med. 1998;2(1):105-8. doi: 10.3892/ijmm.2.1.105.
  20. Kocdor H, Ates H, Aydin S, Cehreli R, Soyarat F, Kemanli P, et al. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer. Drug Des Devel Ther. 2015;9:3899-909. doi: 10.2147/DDDT.S87662.
  21. Toren A, Pismenyuk T, Yalon M, Freedman S, Simon AJ, Fisher T, et al. Zinc enhances temozolomide cytotoxicity in glioblastoma multiforme model systems. Oncotarget. 2016;7(46):74860-71. doi: 10.18632/ oncotarget.11382.
  22. Epstein MM, Kasperzyk JL, Andrén O, Giovannucci EL, Wolk A, Håkansson N, et al. Dietary zinc and prostate cancer survival in a Swedish cohort. Am J Clin Nutr. 2011;93(3):586-93. doi: 10.3945/ajcn. 110.004804.
  23. 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;119(7):1348-52. doi: 10.1002/ lary.20524.