Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model

Concomitant chemotherapy and radiotherapy (CCRT) has recently been shown to improve treatment outcome in a range of solid tumors. Pegylated liposomes have the potential to target drugs directly to tumors and may increase the efficacy and reduce the toxicity of CCRT by selectively delivering radiosen sitizing agents to tumor, as opposed to normal, tissues. In these studies, we have assessed CCRT using pegylated liposome encapsulated doxorubicin (PL ED) and pegylated liposome encapsulated cisplatin (PLEC) against KB head an d neck cancer xenograft tumors in nude mice. The addition of low-dose (2 mg /kg) PLED (P < 0.001) and PI,EC (P < 0.001) significantly increased the eff ect of 4.5 Gy, but not 9 Gy, single-fraction radiotherapy (SFRT), Both PLED and PLEC were significantly more effective than their unencapsulated count erparts in increasing the effect of SFRT, In addition, PLED (P < 0.001) and PLEC (P < 0.05) significantly increased the effect of fractionated radioth erapy (9 Gy in 3 fractions) in two different dosing schedules (2 mg/kg sing le dose or three sequential doses of 0.67 mg/kg), Unencapsulated diethylene triaminepentaacetic acid and pegylated liposomal diethylenetriaminepentaace tic acid were used as controls to test the effect of the liposome vehicle a nd showed no interaction with 4.5 Gy or 9 Gy SFRT (P > 0.1). CCRT was well- tolerated, with no evidence of increased local or systemic toxicity, as com pared with radiotherapy alone. This study is the first to demonstrate the v alue of pegylated liposomes as vehicles for the delivery of radiosensitizin g drugs in CCRT strategies.