Final Report of a Phase III Randomized Trial of Amifostine as a Radioprotectant in Head and Neck Cancer

Todd Doyle, MD
OncoLink Assistant Editor
Last Modified: November 1, 1999

Presenter: Brizel DM et al
Affiliation: Duke University Medical Center

Xerostomia (dry mouth) is a difficult and often permanent complication of head and neck radiotherapy. Life long consequences include difficulty with eating, speaking, and dental complications. This phase III randomized trial of radiation therapy with or without amifostine was performed to evaluate the ability of the radioprotectant drug to decrease acute and long term morbidity.

In addition to acute and chronic xerostomia, both acute and chronic mucositis were evaluated for potential improvement with amifostine. An additional end point that was examined was preservation of the anti-tumor activity of radiation, which could theoretically have been decreased by amifostine.

Three hundred fifteen patients were enrolled, stratified for prognostic factors and randomized to either receive or not receive daily intravenous amifostine. Both post operative and definitively treated patients were evaluated for incidence of grade 2 or higher acute xerostomia, grade 3 or higher mucositis, and grade 2 or higher late xerostomia (1 year after treatment).


  • Significant findings were a reduction in grade 2 or worse acute xerostomia from 78% with RT alone to 51% with daily amifostine.
  • Late xerostomia was reduced from 57% to 34%.
  • Patient benefit questionaires also indicated a benefit in qaulity of life with regards to saliva production.
  • There was no apparent benefit of mucosal protection.
  • No difference in local control of the tumor was identified between the two groups.
  • Amifostine treatment was well tolerated with < 1% incidence of complications (nausea/vomiting, hypotension, allergic reaction, and fever).
Clinical/Scientific Implications:
  • In this study, the daily administration of IV amifostine reduced the incidence of acute and long term xerostomia.
  • The benefit appeared to be achieved without any sacrifice in local tumor control or significant amifostine-related morbidity.
  • This has a significant impact on the quality of life for our head and neck cancer patients, who may be able to continue enjoying simple daily activities such as dining in public and speaking with ease. This makes it an attractive adjunct to treatment with radiation.
  • Future investigations may concentrate further on the potential for mucosal protection, and the possibility to simplify the route of administration with subcutaneous dosing.

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