Barutca Sabri, Meydan Nezih, Akar Harun, Yavasoglu Irfan, Kadikoylu Gurhan, Bolaman Zahit
Department of Internal Medicine, Division of Medical Oncology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Department of Internal Medicine, Division of Nephrology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
Curr Ther Res Clin Exp. 2004 Jan;65(1):113-24. doi: 10.1016/S0011-393X(04)90011-2.
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.
The aim of this study was to analyze the efficacy and tolerability of amifostine in elderly cancer patients.
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.
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.
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.
氨磷汀是一种细胞保护剂，用于预防顺铂所致的肾毒性。它与引起呕吐症状（恶心和呕吐）及短暂性低血压的剂量限制性急性毒性反应相关。
本研究旨在分析氨磷汀在老年癌症患者中的疗效和耐受性。
本项为期18个月的前瞻性对照研究在阿德南·门德雷斯大学医院（土耳其艾登）内科进行。纳入无合并症的成年（年龄40 - <85岁）晚期癌症住院患者。患者分为2组：年龄<70岁（第1组）和≥70岁（第2组）。所有患者均接受氨磷汀 + 顺铂为基础的化疗（CT）。氨磷汀910 mg/m²（最大剂量1500 mg）静脉输注15分钟。在0分钟（基线）、氨磷汀输注8分钟和15分钟以及氨磷汀输注开始后30分钟测量临床收缩压和舒张压（分别为SBP和DBP）。除体格检查外，在每次CT给药前及CT后毒性评估日进行胸部X线检查、心电图检查、血液生化检查（包括血清电解质和肾功能检查）、全血细胞计数及尿常规检查。
连续纳入35例患者（22例男性，13例女性；平均[标准差]年龄61 [12]岁；第1组，n = 22；第2组，n = 13）。患者共接受153个CT周期（中位数，4个周期/患者；第1组，96个周期；第2组, 57个周期）。与基线相比，第1组（P均<0.001）和第2组（分别为P = 0.002和P = 0.006）在氨磷汀输注8分钟时SBP和DBP显著降低。总体而言，20例患者（57.1%）经历≥1次有症状的低血压发作；第1组（11例，50.0%）和第2组（9例，69.2%）之间这些发生率无显著差异。由于低血压，氨磷汀输注中断次数相似（第1组6次，第2组4次[分别占给药次数的6.3%和7.0%]），但均可重新开始输注。在15分钟时，两组平均SBP和DBP值与基线相比均无显著差异。两组基线时平均基线SBP值相似，总体而言，在任何时间点两组间平均SBP和DBP值差异均无统计学意义。所有其他毒性反应相当，且两组中CT后血清肌酐浓度与基线相比均无显著变化。
在本项关于氨磷汀在无合并症的老年晚期癌症患者中的疗效和耐受性研究中，氨磷汀可有效降低顺铂所致的肾毒性，最突出的不良反应是短暂性收缩压和舒张压降低。所有其他毒性反应均为低级别或可预防。研究组间氨磷汀耐受性或毒性反应无显著差异。
