In-vitro cytotoxicity in ovarian-cancer of low-dose continuous exposure to microtubule inhibitors (Paclitaxel taxotere) combined with Cisplatin

We present our data on the cytotoxicity of microtubule inhibitors (paclitaxel and taxotere) and their mode of action against cisplatin-sensitive or -resistant ovarian cancer cell lines in vitro. To try to establish an optimal administration schedule in clinical use, the cytotoxicity of microtubule inhibitors alone and in sequential combination with cisplatin was investigated. With microtubules alone, a marked dose- and schedule-dependent growth inhibition was demonstrated in lower concentrations and only schedule-dependency in higher concentrations. The cytotoxicity of taxotere was approximately 0.8- to 132-fold that of paclitaxel. No cross resistance to cisplatin was observed. In the relation between assay AUC (area under the concentration curve) and growth inhibition, increasing AUC by dose escalation seemed not to be advantageous. In a combination with cisplatin, the treatment of microtubules over 48 h followed by cisplatin administration demonstrated the most effective cytotoxicity in cisplatin-resistant cell line.