Bissery M C, Guénard D, Guéritte-Voegelein F, Lavelle F
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Vitry sur Seine, France.
Cancer Res. 1991 Sep 15;51(18):4845-52.
Taxotere (RP 56976; NSC 628503; N-debenzoyl-N-tert-butoxycarbonyl-10-deacetyl taxol) is a new microtubule stabilizing agent. It is obtained by semisynthesis from a noncytotoxic precursor extracted from the needles of the tree, Taxus baccata L. Taxotere was evaluated for antitumor activity against a variety of transplantable tumors of mice. Taxotere had no marked schedule dependency and was found active by the i.v. and the i.p. routes. Upon i.v. administration, 9 of 11 tumor models tested responded to Taxotere. B16 melanoma was found highly sensitive to Taxotere, with a tumor growth inhibition of 0% and a 3.0 log10 tumor cell kill at the maximum tolerated dose. In the same trial, taxol produced only a 1.1 log10 tumor cell kill at the maximum tolerated dose. Taxotere cured early stage pancreatic ductal adenocarcinoma 03 (6 of 6 cures) and colon adenocarcinoma 38 (7 of 7 cures). It also effected greater than 80% complete regressions of advanced stage disease with both tumors. Taxotere was active against early and advanced stage colon adenocarcinoma 51, with 2.3 and 1.7 log10 cell kill, respectively. Four other tumors responded to a lesser extent: Lewis lung (5.5% tumor growth inhibition), Glasgow osteogenic sarcoma (27.2% tumor growth inhibition), L1210 and P388 leukemias (70 and 54% increase in life span, respectively). Because of its good preclinical activity and its unique mechanism of action, Taxotere has entered Phase I clinical trials.
泰索帝（RP 56976；NSC 628503；N-去苯甲酰基-N-叔丁氧羰基-10-去乙酰基紫杉醇）是一种新型微管稳定剂。它是通过半合成从欧洲红豆杉针叶中提取的一种无细胞毒性的前体物质获得的。对泰索帝针对小鼠多种可移植肿瘤的抗肿瘤活性进行了评估。泰索帝没有明显的给药方案依赖性，静脉注射和腹腔注射给药均显示有活性。静脉给药后，所测试的11种肿瘤模型中有9种对泰索帝有反应。发现B16黑色素瘤对泰索帝高度敏感，在最大耐受剂量下肿瘤生长抑制率为0%，肿瘤细胞杀伤率为3.0 log10。在同一试验中，紫杉醇在最大耐受剂量下仅产生1.1 log10的肿瘤细胞杀伤率。泰索帝治愈了早期胰腺导管腺癌03（6例全部治愈）和结肠腺癌38（7例全部治愈）。它还使这两种肿瘤的晚期疾病完全缓解率超过80%。泰索帝对早期和晚期结肠腺癌51均有活性，细胞杀伤率分别为2.3和1.7 log10。其他四种肿瘤的反应程度较小：Lewis肺癌（肿瘤生长抑制率为5.5%）、格拉斯哥骨肉瘤（肿瘤生长抑制率为27.2%）、L1210和P388白血病（寿命分别延长70%和54%）。由于其良好的临床前活性和独特的作用机制，泰索帝已进入I期临床试验。
