Kisseberth W C, Vail D M, Yaissle J, Jeglum K A, Couto C G, Ward H, Khanna C, Obradovich J E
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.
J Vet Intern Med. 2008 Jan-Feb;22(1):83-8. doi: 10.1111/j.1939-1676.2007.0017.x.
The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial.
To determine the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of carboplatin in tumor-bearing cats. CATS: Fifty-nine cats with measurable solid tumors.
The starting dose of carboplatin was 160 mg/m(2) of body surface area IV. Doses were increased by 20 mg/m(2) in cohorts of 3-14 cats until the MTD was reached.
The 59 cats entered into this multi-institutional phase I study received 1 or more doses of carboplatin at various dosages and were evaluated for toxicity, response to treatment, or both. The MTD was 240 mg/m(2) and neutropenia was the DLT. For the 1st cycle of treatment in 44 cats evaluated for neutropenia, 6 episodes of grade 3 or greater neutropenia occurred on days 7 (n=1), 14 (n=4), and 21 (n=1). There was no evidence of drug-induced nephrotoxicosis or pulmonary edema. Preliminary evidence of antitumor activity was observed in 7 of 59 (11.9%; 95% CI, 5.6-22.8%) cats evaluated for response to treatment. There was 1 complete response (cutaneous hemangiosarcoma) and 6 partial responses (4 injection site sarcomas, 1 oral squamous cell carcinoma, 1 lymphoma). Responses were of short duration (median, 42 days; range, 7-168 days).
The dose of carboplatin recommended to treat tumor-bearing cats is 240 mg/m(2) IV every 3-4 weeks.
关于卡铂在猫体内的剂量，已有在非荷瘤猫身上的轶事性报道和实验研究，但在荷瘤猫中卡铂治疗的剂量尚未在前瞻性临床试验中确定。
确定卡铂在荷瘤猫中的最大耐受剂量（MTD）和剂量限制性毒性（DLT）。
59只患有可测量实体瘤的猫。
卡铂的起始剂量为160mg/m²体表面积静脉注射。剂量以20mg/m²的幅度在每组3 - 14只猫中递增，直至达到MTD。
这59只进入这项多机构I期研究的猫接受了1次或多次不同剂量的卡铂治疗，并对毒性、治疗反应或两者进行评估。MTD为240mg/m²，中性粒细胞减少是DLT。在44只接受中性粒细胞减少评估的猫的第1周期治疗中，在第7天（n = 1）、14天（n = 4）和21天（n = 1）出现了6次3级或更高级别的中性粒细胞减少发作。没有药物诱导的肾毒性或肺水肿的证据。在59只接受治疗反应评估的猫中，有7只（11.9%；95%CI，5.6 - 22.8%）观察到了抗肿瘤活性的初步证据。有1例完全缓解（皮肤血管肉瘤）和6例部分缓解（4例注射部位肉瘤、1例口腔鳞状细胞癌、1例淋巴瘤）。缓解持续时间较短（中位数，42天；范围，7 - 168天）。
推荐用于治疗荷瘤猫的卡铂剂量为每3 - 4周静脉注射240mg/m²。
