Kruczynski A, Colpaert F, Tarayre J P, Mouillard P, Fahy J, Hill B T
Division of Experimental Cancer Research I, Pierre Fabre Research Center, Castres, France.
Cancer Chemother Pharmacol. 1998;41(6):437-47. doi: 10.1007/s002800050764.
Vinflunine, or 20',20'-difluoro-3',4'-dihydrovinorelbine, is a novel Vinca alkaloid obtained by hemisynthesis using superacidic chemistry. The most impressive structural modification of this vinorelbine derivative was the selective introduction of two fluorine atoms at the 20' position, a part of the molecule previously inaccessible by classic chemistry. The antitumor activity of vinflunine was evaluated against a range of transplantable murine and human tumors. Vinflunine exhibited marked activity against murine P388 leukemia grafted i.v. when given i.p. in single or multiple doses according to various schedules or in single i.v. or p.o. doses. Increases in life span achieved with vinflunine, as assessed by T/C ratios, ranged from 200% to 457% and proved markedly superior to those of 129-186% obtained with the other Vinca alkaloids tested. Against s.c.-implanted B16 melanoma, multiple i.p. administration of vinflunine proved active in terms of both survival prolongation and tumor growth inhibition, with optimal T/C values and relative areas under the tumor growth curves (rAUC) being 24% and 36%, respectively. The extent of this activity was superior to that noted for vinorelbine under the same experimental conditions. Growth inhibition of human tumor xenografts LX-1 (lung) and MX-1 (breast) was also observed following four weekly i.p. injections of vinflunine as reflected by optimal T/C values of 23% and 26%, respectively, and significant differences in the rAUCs noted for treated versus control animals. It was also noticeable that vinflunine induced considerably more prolonged inhibitory effects on tumor growth than did vinorelbine. These results demonstrate that vinflunine is well tolerated and is definitively active against a range of experimental animal tumor models. Vinflunine activity has been documented in terms of both survival prolongation and tumor growth inhibition, with definite superiority over vinorelbine being shown in each tumor model evaluated.
长春氟宁，即20'，20'-二氟-3'，4'-二氢长春瑞滨，是一种通过使用超强酸化学半合成获得的新型长春花生物碱。这种长春瑞滨衍生物最引人注目的结构修饰是在20'位选择性引入两个氟原子，这是经典化学以前无法触及的分子部分。评估了长春氟宁对一系列可移植的小鼠和人类肿瘤的抗肿瘤活性。当按照各种给药方案腹腔注射单剂量或多剂量或静脉注射或口服单剂量时，长春氟宁对静脉接种的小鼠P388白血病表现出显著活性。通过T/C比值评估，长春氟宁实现的寿命延长范围为200%至457%，明显优于测试的其他长春花生物碱所获得的129%-186%。对于皮下植入的B16黑色素瘤，多次腹腔注射长春氟宁在延长生存期和抑制肿瘤生长方面均被证明具有活性，最佳T/C值和肿瘤生长曲线下的相对面积（rAUC）分别为24%和36%。在相同实验条件下，这种活性程度优于长春瑞滨。在每周腹腔注射四次长春氟宁后，也观察到对人肿瘤异种移植瘤LX-1（肺癌）和MX-1（乳腺癌）的生长抑制，分别表现为最佳T/C值为23%和26%，以及治疗组与对照组动物的rAUC存在显著差异。还值得注意的是，长春氟宁对肿瘤生长的抑制作用比长春瑞滨持续时间长得多。这些结果表明，长春氟宁耐受性良好，对一系列实验动物肿瘤模型具有明确的活性。长春氟宁的活性已在延长生存期和抑制肿瘤生长方面得到证实，在评估的每个肿瘤模型中均显示出明显优于长春瑞滨。
