Efficacy and tolerability of amifostine in elderly cancer patients

Abstract

Background: Amifostine is a cytoprotective agent used to prevent cisplatin nephrotoxicity. It is associated with dose-limiting acute toxicities of emetic symptoms (nausea and vomiting) and transient hypotension.

Objective: The aim of this study was to analyze the efficacy and tolerability of amifostine in elderly cancer patients.

Methods: This 18-month, prospective, comparative study was conducted at the Department of Internal Medicine, Adnan Menderes University Hospital (Aydin, Turkey). Adult (aged 40-<85 years) hospitalized patients with advanced-stage cancer without comorbid diseases were enrolled. Patients were divided into 2 groups: age <70 years (group 1) and ≥70 years (group 2). All patients were treated with amifostine + cisplatin-based chemotherapy (CT). Amifostine 910 mg/m(2) (maximum, 1500 mg) was administered as a 15-minute IV infusion. Clinical systolic and diastolic blood pressures (SBP and DBP, respectively) were measured at 0 minute (baseline), at 8 and 15 minutes of amifostine infusion, and at 30 minutes after the start of amifostine infusion. In addition to physical examination, chest radiography, electrocardiography, blood chemistry (including serum electrolytes and renal function tests), complete blood count, and complete urinalyses were performed before each CT administration and at the post-CT day of toxicity assessment.

Results: Thirty-five consecutive patients were enrolled (22 men, 13 women; mean [SD] age, 61 [12] years; group 1, n = 22; group 2, n = 13). Patients received a total of 153 CT cycles (median, 4 cycles/patient; group 1, 96 cycles; group 2, 57 cycles). Amifostine caused significant SBP and DBP reductions at 8 minutes of infusion compared with baseline in groups 1 (both P < 0.001) and 2 (P = 0.002 and P = 0.006, respectively). Overall, 20 patients (57.1%) experienced ≥ 1 symptomatic hypotensive episode; these rates were not significantly different between groups 1 (11 cases, 50.0%) and 2 (9 cases, 69.2%). Amifostine infusion was interrupted a similar number of times (6 times in group 1 and 4 times in group 2 [6.3% and 7.0% of administrations, respectively]) due to hypotension, but could be restarted in all. At 15 minutes, mean SBP and DBP values were not significantly different from baseline in either group. The mean baseline SBP values were similar between groups at baseline, and, overall, the differences in mean SBP and DBP values were not significant between groups at any time point. All other toxicities were comparable, and serum creatinine concentrations did not change significantly from baseline with CT in either group.

Conclusions: In this study of the efficacy and tolerability of amifostine in elderly patients with advanced-stage cancer without comorbid diseases, amifostine was effective in reducing cisplatin-induced nephrotoxicity, with transient systolic and diastolic hypotension being the most prominent adverse effect. All other toxicities were either low grade or preventable. No significant differences in amifostine tolerability or toxicities were observed between the study groups.

Keywords: adverse effects; amifostine; cisplatin; elderly cancer patients; nephrotoxicity; tolerability.