Zinc sulfate in the prevention of radiation-induced oropharyngeal mucositis: a prospective, placebo-controlled, randomized study

Int J Radiat Oncol Biol Phys. 2004 Jan 1;58(1):167-74. doi: 10.1016/s0360-3016(03)01562-1.


Purpose: To determine the effect of oral zinc sulphate supplementation on radiation-induced oropharyngeal mucositis in patients with head-and-neck cancer.

Materials and methods: Thirty patients with head-and-neck cancer were randomly assigned to receive either zinc sulfate or placebo. Primary tumors were localized in the larynx in 14 patients, in the nasopharynx in 4, in the oral cavity in 4, in a salivary gland in 1, in the maxillary sinus in 1, in neck nodes (lymphoma presenting primarily) in 3 and in neck metastases from an unknown primary in 3. In the placebo group, 3 patients were excluded; 1 patient died during treatment, 1 left the study, and 1 did not come to the 6 week control visit. The patients were treated with telecobalt radiotherapy at conventional fractionation (2 Gy/fraction, five fractions weekly, for 20-35 fractions within 4-7 weeks). The median radiation dose was 6400 cGy (4000-7000 cGy). Oral mucositis was assessed by two independent physicians, experts in radiation oncology, using the Radiation Therapy Oncology Group Acute Radiation Morbidity Scoring criteria.

Results: In the zinc sulfate group, Grade 3-4 mucositis was not detected in any patient; Grade 0 mucositis was detected in 2, and Grade 1 in 8, and Grade 2 in 5 patients. In the placebo group, Grade 2 mucositis was detected in 4 and Grade 3 in 8 patients. We observed that the degree of mucositis in the patients in the zinc sulfate group was significantly lower than that in the placebo group (p < 0.05). Confluent mucositis developed earlier in the placebo group than in the zinc sulfate group after the onset of treatment (p < 0.05) and started to improve sooner in the zinc sulfate group than in the placebo group (p < 0.05).

Conclusions: Zinc sulfate is beneficial in decreasing the severity of radiation-induced mucositis and oral discomfort. These results should be confirmed by additional evaluation in randomized studies with a larger number of patients.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Head and Neck Neoplasms / radiotherapy*
  • Humans
  • Male
  • Middle Aged
  • Mouth Mucosa / radiation effects
  • Oral Hygiene
  • Prospective Studies
  • Radiation Injuries / prevention & control*
  • Radiation-Protective Agents / therapeutic use*
  • Statistics, Nonparametric
  • Stomatitis / etiology
  • Stomatitis / prevention & control*
  • Zinc Sulfate / therapeutic use*


  • Radiation-Protective Agents
  • Zinc Sulfate