Antitumor activity of paclitaxel-2'-glycinate conjugated to poly(ethylene glycol): a water-soluble prodrug.

Synthesis and in vivo antitumor activity evaluation of water-soluble poly(ethylene glycol) (PEG)-conjugated paclitaxel-2'-glycinate (6) are reported. This prodrug demonstrated enhanced antitumor activity and less toxicity in a P388/0 murine leukemia model when compared, on an equimolar basis, with native paclitaxel formulated in Cremophor/ethanol. Employing 6 in the treatment of HT-29, A549 and SKOV3 solid tumor-bearing xenografted mice demonstrated significant antitumor activity. The outstanding performance of 6 may be attributed partly to the tripartate nature of the prodrug.