Hahn K A, McEntee M F, Daniel G B, Legendre A M, Nolan M L
Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
Am J Vet Res. 1997 Jun;58(6):677-9.
To determine prevalence and severity of carboplatin-induced dose-limiting toxicoses in the cat.
9 healthy, 6- to 7-month-old cats weighing 4.7 (range, 3.0 to 6.5) kg.
Cats were given a single i.v. bolus of carboplatin at a dosage of 150 (n = 3), 200 (n = 3), or 250 (n = 3) mg/m2 of body surface area.
Dose-limiting neutropenia and thrombocytopenia were significant in all cats given carboplatin at 200 or 250 mg/m2. Weight loss, changes in appetite, and evidence of respiratory difficulty, as well as vomiting, diarrhea, or lethargy were not observed at any time during the 28-day period. At a highest dosage (250 mg/m2), the neutrophil nadir (560 +/- 303 neutrophils/microliters) was observed on day 17 and the platelet count nadir (96,500 +/- 11,815 platelets/microliters) was observed on day 14 after carboplatin administration.
Carboplatin appears to be safe and clinically well-tolerated when given i.v. as a single bolus at a dosage of 200 mg/m2 to clinically normal cats. The dose-limiting toxicity of a single i.v. administered bolus is neutropenia. The nadir of a 200 mg/m2 i.v. administered dose occurs on day 17 (1,110 +/- 165 neutrophils/microliters) and neutropenia (< 2,000 neutrophils/microliters) lasts from day 14 through day 25 after carboplatin administration.
The fatal dose-related pulmonary toxicosis observed in cisplatin-treated cats was inapparent in carboplatin-treated cats. To adequately determine the therapeutic role of carboplatin in tumor-bearing cats, a moderately tolerated dose of carboplatin of 200 mg/m2 given i.v. once every 4 weeks should be considered.
确定卡铂诱导的猫剂量限制性毒性反应的发生率和严重程度。
9只健康的6至7月龄猫,体重4.7(范围3.0至6.5)千克。
给猫静脉注射单次大剂量卡铂,剂量为150(n = 3)、200(n = 3)或250(n = 3)毫克/平方米体表面积。
所有接受200或250毫克/平方米卡铂治疗的猫均出现显著的剂量限制性中性粒细胞减少和血小板减少。在28天期间的任何时候均未观察到体重减轻、食欲变化、呼吸困难迹象以及呕吐、腹泻或嗜睡。在最高剂量(250毫克/平方米)时,卡铂给药后第17天观察到中性粒细胞最低点(560±303个中性粒细胞/微升),第14天观察到血小板计数最低点(96,500±11,815个血小板/微升)。
对于临床正常的猫,以200毫克/平方米的剂量静脉注射单次大剂量卡铂时,卡铂似乎是安全的且临床耐受性良好。单次静脉注射大剂量的剂量限制性毒性是中性粒细胞减少。200毫克/平方米静脉注射剂量的最低点出现在第17天(1,110±165个中性粒细胞/微升),中性粒细胞减少(<2,000个中性粒细胞/微升)在卡铂给药后第14天至第25天持续存在。
在顺铂治疗的猫中观察到的致命剂量相关肺部毒性反应在卡铂治疗的猫中不明显。为了充分确定卡铂在荷瘤猫中的治疗作用,应考虑每4周静脉注射一次200毫克/平方米的中等耐受剂量的卡铂。