Enhanced Antitumor Activity of Irofulven in Combination with Antimitotic Agents

The aim of this study was to determine theantitumor activity of irofulven whenadministered in combination with a varietyof antimitotic agents. Irofulven incombination with either paclitaxel ordocetaxel demonstrated synergistic activityin both the in vitro and invivo studies. The majority of xenograftbearing animals that received suboptimal (< MTD) doses of irofulven and a taxanedemonstrated complete cures. In contrast,in vitro studies produced either anadditive or an antagonistic effect whenirofulven was combined with otherantimitotic agents such as vinca alkaloids,rhizoxin, s-trityl cysteine, orallocolchicine. Xenograft studies ofirofulven and vinca alkaloids reflectedin vitro results, as the tumorresponse in combination treated animals wasless than the response in irofulven(monotherapy) treated animals. Theseresults indicate that the therapeuticactivity of irofulven is enhanced whencombined with taxanes, and warrant furtherevaluation of these combinations.