Randomized Phase III Trial of Postoperative Radiochemotherapy ± Amifostine in Head and Neck Cancer

Abstract

According to our results, there is a radioprotective effect on salivary glands and a potential effect on oral mucosa by amifostine in postoperative radiotherapy combined with carboplatin. To improve the radio- and chemoprotective effects of amifostine in clinical practice, the application of a higher dose (> 250 mg) seems to be necessary.

Systematic review of amifostine for the management of oral mucositis in cancer patients

“…Furthermore, the diagnostic criteria for oral mucositis were not adequately described. The infusion of 250 mg of amifostine 15 min prior to radiotherapy reduced the severity of oral mucositis in the experimental when compared to the control group, but the difference did not reach significant levels in one, non-blinded, non-placebo-controlled study [9]. Grade 3 oral mucositis was reduced when compared to historical controls (40 versus 70 %) in patients who received 500 mg amifostine within 1 h before radiotherapy [11].…”

“…In patients undergoing chemoradiotherapy for head and neck cancer, eight articles were reviewed [4,5,7,9,11,29,30,39 ]. In all eight studies, amifostine was administered for prevention.…”

“…This might possibly prevent the up-regulation of inflammatory pathways related to cancer therapy toxicity and, thus, may allow compliance with the planned treatment regimens while preserving the patient's quality of life. Amifostine, administered intravenously, has been shown to reduce the incidence of acute and late xerostomia in head and neck cancer patients who receive radiotherapy, with or without chemotherapy [4][5][6][7][8][9][10][11][12][13]. The American Society of Clinical Oncology has recommended that the cytoprotective effect of amifostine "may be considered" for the prevention of cisplatin-associated nephrotoxicity, for the reduction of grade 3-4 neutropenia and to decrease acute and late xerostomia with fractionated radiotherapy for head and neck cancer [14,15].…”

Efficacy and tolerability of amifostine in elderly cancer patients

“…The effects of amifostine infusion on the clinical BP values of the study groups are shown in Table III and Table IV. The mean (SD) of median per patient reductions in SBP and DBP values at 8 minutes of infusion were significant compared with baseline in group 1 (16 [12] and 8 [7] mm Hg, respectively; both P < 0.001), group 2 (18 [12] and 13 [8] mm Hg; P --0.002 and P --0.006, respectively), and in all patients (17 [11] and 10 [7] mm Hg; both P< 0.001). The mean reductions at 8 minutes in groups 1 and 2 for SBP were similar.…”

The Cytoprotective Effect of Amifostine Against Radiation Induced Toxicity

“…In addition, the observed rates of grade 2 acute xerostomia and grade 3 oral mucositis in the placebo group were unexpectedly low, reducing the ability of the study to show significant benefit with amifostine. In contrast, studies in which amifostine was administered within 30 minutes of radiotherapy have shown promise with regard to protection from acute and chronic xerostomia (Andonadou et al, 2002;Brizel et al, 2000;Vacha et al, 2003). Taken together, it appears that administration of amifostine within 30 minutes of radiotherapy or chemoradiotherapy may provide optimal benefit for cytoprotection of normal tissues.…”