Radiochemotherapy with amifostine cytoprotection for head and neck cancer

Abstract

A randomized study was conducted to evaluate the protective activity of amifostine (A) against the dose-limiting toxicities of radiochemotherapy (RCT). Patients with head and neck cancer received radiotherapy (2 Gy/day 5 days a week up to 60 Gy) with carboplatin 70 mg/m2 on days 1-5 and 21-25 inclusive. Patients either received RCT alone (n = 14) or RCT + A at a dose of 500 mg prior to treatment with carboplatin (n = 25). There was a significant reduction in the incidence of grade 3/4 mucositis (P < 0.0001), acute grade 2 xerostomia (P < 0.0001) and grade 3/4 thrombocytopenia (P = 0.012) in these patients who received A. The incidence of grade 2 late xerostomia at 12 months is 16.7% and the incidence of loss of taste is 0% in patients treated with A, as opposed to 54.5% and 63.6% in patients who received RCT alone. There were 18 (72%) complete responses (CR) and 6 (24%) partial responses (PR) in patients who received A, compared with 6 (43%) CR and 6 PR (43%) in patients treated with RCT alone. The disease-free survival at 12 months is 85.7% in the RCT + A arm and 78.6% in the RCT alone arm. The use of amifostine reduces the incidence and severity of acute and late toxicities associated with RCT whilst preserving antitumour activity.

The Effect of Amifostine on Acute and Late Radiation Side Effects in Head and Neck Cancer Patients

“…36 In a study by Buntzel et al, the difference in grade 2 xerostomia was significant between ART and RT arms (p=0.0001). 39 By contrast, Munter et al did not show any difference in comparison to other studies; however, the majority of the patients recieved RT without CT. 31 In the present study the effect of amifostine on saliva became significant starting at nine months of follow-up and persisted thereafter. The incidence of grade 3 xerostomia at 9, 12, and 15 months of follow-up was higher in the RT group than in the ART group.…”

“…Several studies reported that the clinical outcome was not affected by amifostine. 33,38,39 In addition, the difference in overall survival rates in two studies was not significant between the groups. 14,35 In our study no significant difference was observed between the groups in terms of the median overall survival.…”

“…40 Although subcutaneous administration was tolerated to a greater degree than intravenous administration, hypotension and nausea were reported to be the most common side effects. 18,39,43,44 Koukourakis et al reported nausea in 28%, vomiting in 4%, and fatigue in 16% of patients that received amifostine subcutaneously, whereas hypotension was not observed in any of the patients. 44 In a study by Ozsahin et al, despite the fact that amifostine was interrupted due to nausea in 33% of patients and due to hypotension in 18%, it was well tolerated in nearly half of the patients.…”

“…During 12 months of follow-up, significantly fewer patients in the ART+CT group had grade 2 xerostomia than those in the RT+CT group (17% vs. 55%), and amifostine significantly decreased the rate of severe dermatitis, loss of taste, and dysphagia. 39,40 In a series of 50 cases, Antonadou et al compared patients that underwent RT+CT with or without amifostine and side effects were recorded at certain intervals. 38 They reported that treatment was interrupted due to grade 4 mucositis in six patients (28%) in the amifostine group and in 12 patients (52%) in the control group.…”

“…41 In another study, grade 3-4 thrombocytopenia and leukopenia were not observed in any of the patients that received amifostine during RT, and the difference between the patients that did and did not receive amifostine was significant. 39,40 Momm et al reported that only the leukocyte count was maintained in patients that received amifostine. 42 In contrast, Antonadou et al did not observe a protective effect of amifostine against hematologic side effects.…”