Supportive Care in Cancer

, Volume 14, Issue 1, pp 44–51

Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck cancer patients receiving radiotherapy

  • Ourania Nicolatou-Galitis
  • Aristea Velegraki
  • Anastasia Sotiropoulou-Lontou
  • Konstantinos Dardoufas
  • Vassilis Kouloulias
  • Konstantinos Kyprianou
  • Georgia Kolitsi
  • Christos Skarleas
  • George Pissakas
  • Vassilis S. Papanicolaou
  • John Kouvaris
Original Article


Goal of work

The aim of the study is to evaluate the effect of fluconazole antifungal prophylaxis on the severity of mucositis in head and neck cancer patients receiving radiotherapy.

Patients and methods

Sixty-three patients, with malignant head and neck tumor, eligible to receive radiotherapy, entered the study. Thirty-four patients (group A) received 100 mg/day of fluconazole prophylaxis during radiotherapy and were compared with 29 patients, who received radiotherapy alone (group B). The two groups were similar in terms of patients and radiotherapy characteristics. Smear to test for Candida carriage was taken before and after radiotherapy. Oral candidiasis was diagnosed using the criteria described before. Oral mucositis was recorded according to EORTC/RTOG criteria.

Main results

A significant reduction of severe mucositis at the end of radiotherapy (14.7 vs 44.8%, p=0.018) and of interruptions (0 vs 17.2%, p=0.017) was observed in group A. Candidiasis was prevented (0 vs 34.5%, p=0.001), with a significant reduction of Candida carriage of 40.7% (p=0.001).


Fluconazole prophylaxis showed a significant beneficial impact on the severity of mucositis and on radiotherapy interruptions in this group of patients. The current study provides data on the build of a randomized controlled trial on the effect of fluconazole prophylaxis on treatment schedule and quality of life of the patients during head and neck radiotherapy.


Antifungal prophylaxis Fluconazole Oral candidiasis Oral mucositis Radiotherapy 


  1. 1.
    Arendorf TM, Walker DM (1980) The prevalence and intra-oral distribution of Candida albicans in man. Arch Oral Biol 25:1–10CrossRefPubMedGoogle Scholar
  2. 2.
    Chen TY, Webster JH (1974) Oral Monilia study on patients with head and neck cancer during radiotherapy. Cancer 34:246–249Google Scholar
  3. 3.
    Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346CrossRefPubMedGoogle Scholar
  4. 4.
    Dahiya MC, Redding SW, Dahiya RS et al (2003) Oropharyngeal candidiasis caused by non-albicans yeast in patients receiving external beam radiotherapy for head–neck cancer. Int J Radiat Oncol Biol Phys 57:79–83CrossRefPubMedGoogle Scholar
  5. 5.
    El-Sayed S, Nabid A, Shelley W et al (2002) Prophylaxis of radiation-associated mucositis in conventionally treated patients with head and neck cancer: a double-blind, phase III, randomized, controlled trial evaluating the clinical efficacy of an antimicrobial lozenge using a validated mucositis scoring system. J Clin Oncol 20:3956–3963CrossRefPubMedGoogle Scholar
  6. 6.
    Epstein JB, Freilich MM, Nhu DL (1993) Risk factors for oropharyngeal candidiasis in patients who receive radiation therapy for malignant conditions of the head and neck. Oral Surg Oral Med Oral Pathol 76:169–174PubMedGoogle Scholar
  7. 7.
    Koc M, Aktas E (2003) Prophylactic treatment of mycotic mucositis in radiotherapy of patients with head and neck tumors. Jpn J Clin Oncol 33:57–60CrossRefPubMedGoogle Scholar
  8. 8.
    Kollia K, Arabatzis M, Kostoula O et al (2003) Clavispora (Candida) lusitaniae susceptibility profiles and genetic diversity in three tertiary hospitals (1998–2001). Int J Antimicrob Agents 22:455–457Google Scholar
  9. 9.
    Kwong DLW, Sham JST, Chua DTT, Choy DTK, Au GKU, Wu PM (1997) The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys 39:703–710CrossRefPubMedGoogle Scholar
  10. 10.
    Makkonen TA, Minn H, Jekunen A, Vilja P, Tuominen J, Joensuu H (2000) Granulocyte-macrophage colony-stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study. Int J Radiat Oncol Biol Phys 46:525–534CrossRefPubMedGoogle Scholar
  11. 11.
    Martin MV, Al-Tikriti U, Bramley PA (1981) Yeast flora of the mouth and skin during and after irradiation for oral and laryngeal cancer. J Med Microbiol 14:457–467PubMedGoogle Scholar
  12. 12.
    Mucke R, Kaben U, Libera T et al (1998) Fluconazole prophylaxis in patients with head and neck tumours undergoing radiation and radiochemotherapy. Mycoses 41:421–423PubMedGoogle Scholar
  13. 13.
    Nicolatou O, Sotiropoulou-Lontou A, Skarlatos J, Kyprianou K, Kolitsi G, Dardoufas K (1998) A pilot study of the effect of granulocyte-macrophage colony-stimulating factor on oral mucositis in head and neck cancer patients during X-radiation therapy : a preliminary report. Int J Radiat Oncol Biol Phys 42:551–556CrossRefPubMedGoogle Scholar
  14. 14.
    Nicolatou-Galitis O, Dardoufas K, Markoulatos P et al (2001) Oral pseudomembranous candidiasis, herpes simplex virus-1 infection, and oral mucositis in head and neck cancer patients receiving radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash. J Oral Pathol Med 30:471–480Google Scholar
  15. 15.
    Nicolatou-Galitis O, Sotiropoulou-Lontou A, Velegraki A et al (2003) Oral candidiasis in head and neck cancer patients receiving radiotherapy, with amifostine cytoprotection. Oral Oncol 39:397–401CrossRefPubMedGoogle Scholar
  16. 16.
    Paula CR, Sampaio MCC, Birman EG, Siqueira AM (1990) Oral yeasts in patients with cancer of the mouth, before and during radiotherapy. Mycopathologia 112:119–124CrossRefPubMedGoogle Scholar
  17. 17.
    Redding SW, Zellars RC, Kirkpatrick WR et al (1999) Epidemiology of oropharyngeal Candida colonization and infection in patients receiving radiation for head and neck cancer. J Clin Microbiol 37:3896–3900PubMedGoogle Scholar
  18. 18.
    Rossie KM, Taylor J, Beck FM, Hodson SE, Blozis GG (1987) Influence of radiation therapy on oral Candida albicans colonization: a quantitative assessment. Oral Surg Oral Med Oral Pathol 64:698–701PubMedGoogle Scholar
  19. 19.
    Samaranayake LP, MacFarlane TW (1990) Oral candidosis. Wright, London, p 7Google Scholar
  20. 20.
    Sebti A, Kiehn TE, Perlin D et al (2001) Candida dubliniensis at a Cancer Center. CID 32:1034–1038CrossRefGoogle Scholar
  21. 21.
    Sonis ST (2004) A biological approach to mucositis. J Support Oncol 2:21–36PubMedGoogle Scholar
  22. 22.
    Spijkervet FKL, van Saene HKF, Panders AK, Vermey A, Mehta DM (1989) Scoring irradiation mucositis in head and neck cancer patients. J Oral Pathol Med 18:167–171PubMedGoogle Scholar
  23. 23.
    Spijkervet FKL, van Saene HKF, van Saene JJM et al (1991) Effect of selective elimination of the oral flora on mucositis in irradiated head and neck cancer patients. J Surg Oncol 46:167–173PubMedGoogle Scholar
  24. 24.
    Trotti A, Bellm LA, Epstein JB et al (2003) Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy : a systematic literature review. Radiother Oncol 66:253–262CrossRefPubMedGoogle Scholar
  25. 25.
    Wijers OB, Levendag PC, Harms ERE et al (2001) Mucositis reduction by selective elimination of oral flora in irradiated cancers of the head and neck: a placebo-controlled double-blind randomized study. Int J Radiat Oncol Biol Phys 50:343–352CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Ourania Nicolatou-Galitis
    • 1
    • 8
  • Aristea Velegraki
    • 2
  • Anastasia Sotiropoulou-Lontou
    • 3
  • Konstantinos Dardoufas
    • 4
  • Vassilis Kouloulias
    • 4
  • Konstantinos Kyprianou
    • 5
  • Georgia Kolitsi
    • 6
  • Christos Skarleas
    • 5
  • George Pissakas
    • 3
  • Vassilis S. Papanicolaou
    • 7
  • John Kouvaris
    • 4
  1. 1.Department of Oral Pathology and Surgery, Dental Oncology Unit, School of DentistryNational and Kapodistrian University of AthensAthensGreece
  2. 2.Mycology Reference Laboratory, Department of Microbiology, School of MedicineNational and Kapodistrian University of AthensAthensGreece
  3. 3.2nd Radiotherapy DepartmentO Aghios Savas HospitalAthensGreece
  4. 4.Department of Radiotherapy, School of Medicine, Aretaieion University HospitalNational and Kapodistrian University of AthensAthensGreece
  5. 5.Radiation Department, Athinaion HospitalEuromedicaAthensGreece
  6. 6.Radiation Oncology Department of Hygeia HospitalAthensGreece
  7. 7.Department of Maxillofacial SurgeryO Aghios Savas HospitalAthensGreece
  8. 8.AthensGreece

Personalised recommendations