Radiation Induced Chemosensitization: Potentiation of Antitumor Activity of Polymer-Drug Conjugates

摘要

This study was aimed at evaluating the enhanced antitumor response to radiotherapy by poly(L-glutamic acid)- paclitaxel (PG-TXL) conjugate. We compared the ability of paclitaxel and PG-TXL to sensitize radioresponse using both tumor growth delay and tumor curability as the end points. Furthermore, the effect of treatment schedule on the radiosensitizing activity of PG-TXL as well as the effect of PG-TXL on the sensitivity of normal tissues to radiation was also studied. Our data demonstrate significant synergistic interaction between PG-TXL and tumor radiation. Compared to paclitaxel, PG-TXL enhanced the response of tumors to radiation for approximately 4 folds. Importantly, the enhanced antitumor activity was achieved without apparent effect on the normal tissues. Our results also suggest that PG-TXL may exert its radiosensitizing effect through multiple mechanisms, one of which being sustained release of paclitaxel in the tumor from PG-TXL. This study has lead to a National Cancer Institute- sponsored clinical study that will be initiated at the University of Texas M. D. Anderson Cancer Center upon regulatory approval.