Boven E, Venema-Gaberscek E, Erkelens C A, Bissery M C, Pinedo H M
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Ann Oncol. 1993 Apr;4(4):321-4. doi: 10.1093/oxfordjournals.annonc.a058491.
The new cytostatic agent taxol has clearly demonstrated its effectiveness in ovarian cancer patients. The synthesis of drugs related to taxol could overcome its limited natural supply and may have additional benefits, such as greater efficacy or better solubility. Taxotere (RP 56976, NSC 628503) is such a compound. We investigated the drug for its antitumor activity in human ovarian cancer xenografts.
Five human ovarian cancer lines were selected with respect to differences in histological sub-types, growth rates and chemosensitivity to conventional cytostatic agents. Tumors were implanted as fragments s.c. into both flanks of female nude mice (Hsd: athymic nude-nu). Treatment was started in groups of 5-8 mice at the time mean tumor volume measured 50-150 mm3. Taxotere was injected i.v. weekly x 2. Drug efficacy was expressed as the maximum percentage of growth inhibition of treated tumors as compared to control tumors.
At the maximum tolerated dose of 15-20 mg/kg for weekly i.v. x 2 injections, taxotere induced a mean weight loss of 10%-15% of the initial weight within 2 weeks after the first injection. The maximum percentage of growth inhibition obtained was > or = 50% in 4/5 lines and > or = 90% in 3/5 lines. In 2 lines, taxotere appeared more effective than cisplatin, cyclophosphamide or doxorubicin, drugs studied previously at maximum tolerated doses in the same tumor lines.
Our findings in human ovarian cancer xenografts hold promise for the efficacy of taxotere in this type of disease in the clinic.
新型细胞抑制剂紫杉醇已在卵巢癌患者中明确显示出其有效性。与紫杉醇相关的药物合成可克服其天然供应有限的问题，并且可能具有其他益处，例如更高的疗效或更好的溶解性。泰索帝（RP 56976，NSC 628503）就是这样一种化合物。我们研究了该药物在人卵巢癌异种移植瘤中的抗肿瘤活性。
根据组织学亚型、生长速率以及对传统细胞抑制剂的化疗敏感性差异，选择了5种人卵巢癌细胞系。将肿瘤组织切成碎片皮下植入雌性裸鼠（Hsd：无胸腺裸鼠-nu）的双侧胁腹。当平均肿瘤体积达到50 - 150立方毫米时，将5 - 8只小鼠分为一组开始治疗。泰索帝通过静脉注射给药，每周1次，共2次。药物疗效以治疗组肿瘤生长抑制的最大百分比与对照组肿瘤进行比较来表示。
在每周静脉注射2次、最大耐受剂量为15 - 20毫克/千克的情况下，首次注射后2周内，泰索帝导致平均体重减轻了初始体重的10% - 15%。在5种细胞系中，有4种获得的最大生长抑制百分比≥50%，有3种≥90%。在2种细胞系中，泰索帝似乎比顺铂、环磷酰胺或阿霉素更有效，而之前在相同肿瘤细胞系中以最大耐受剂量研究过这些药物。
我们在人卵巢癌异种移植瘤中的研究结果表明，泰索帝在临床上对这类疾病具有疗效前景。
