Théon A P, VanVechten M K, Madewell B R
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Am J Vet Res. 1996 Feb;57(2):205-10.
To develop a slow-release carboplatin formulation for intratumoral administration to cats.
Preliminary study to analyze pharmacokinetic effects of purified sesame oil in the carboplatin formulation for intratumoral administration, and a second study to evaluate the efficacy and toxicosis of intratumoral administration of carboplatin in purified sesame oil.
23 cats with squamous cell carcinomas of the nasal plane.
Eight cats with advanced-stage tumors were submitted to intratumoral administration of 100 mg of carboplatin/m2 of body surface area, with or without purified sesame oil, using a two-period, cross-over design. Fifteen additional cats were treated by intratumoral administration of carboplatin in purified sesame oil. Four weekly intratumoral chemotherapy injections of carboplatin in purified sesame oil at a dosage of 1.5 mg/cm3 of tissue were given.
Purified sesame oil in the formulation significantly reduced systemic exposure to carboplatin and drug leakage from the sites of injection. Cumulative effects of repeated intratumoral administrations on plasma concentrations of carboplatin were not observed. Systemic toxicosis was not observed, and local toxicosis was minimal. Healing of ulcerated lesions was not compromised. Rates of complete clinical tumor clearance and complete response were 67 and 73.3%, respectively. Product-limit estimates of mean progression-free survival times was 16 +/- 3.3 months. The 1-year progression-free survival rate was 55.1 +/- 13%. Local recurrence was observed in 7 cats; 4 had marginal tumor recurrence, and 3 had in-field and marginal tumor recurrence.
Intratumoral carboplatin chemotherapy is safe and effective for cats with squamous cell carcinoma of the nasal plane. Future studies to improve treatment efficacy could include evaluation of increased dose-intensity as well as combination of this modality with radiotherapy.
Intratumoral administration of carboplatin in a water-sesame-oil emulsion was found to be a practical and effective new treatment for facial squamous cell carcinomas in cats.
开发一种用于猫瘤内给药的缓释卡铂制剂。
初步研究分析纯化芝麻油在瘤内给药卡铂制剂中的药代动力学效应,第二项研究评估卡铂在纯化芝麻油中瘤内给药的疗效和毒性。
23只患有鼻平面鳞状细胞癌的猫。
8只患有晚期肿瘤的猫采用两期交叉设计,接受瘤内注射100mg/m²体表面积的卡铂,加或不加纯化芝麻油。另外15只猫接受瘤内注射纯化芝麻油中的卡铂治疗。每周进行4次瘤内化疗注射,卡铂在纯化芝麻油中的剂量为1.5mg/cm³组织。
制剂中的纯化芝麻油显著降低了卡铂的全身暴露以及药物从注射部位的渗漏。未观察到重复瘤内给药对卡铂血浆浓度的累积效应。未观察到全身毒性,局部毒性最小。溃疡病变的愈合未受影响。临床肿瘤完全清除率和完全缓解率分别为67%和73.3%。平均无进展生存时间的乘积限估计值为16±3.3个月。1年无进展生存率为55.1±13%。7只猫出现局部复发;4只边缘肿瘤复发,3只瘤内和边缘肿瘤复发。
瘤内卡铂化疗对患有鼻平面鳞状细胞癌的猫是安全有效的。未来提高治疗效果的研究可包括评估增加剂量强度以及这种治疗方式与放疗的联合应用。
发现水-芝麻油乳剂瘤内注射卡铂是治疗猫面部鳞状细胞癌的一种实用有效的新方法。