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
radiosensitizing agents to
tumor, as opposed to normal, tissues. In these studies, we have assessed CCRT using pegylated
liposome encapsulated
doxorubicin (
PLED) and pegylated
liposome encapsulated
cisplatin (PLEC) against KB
head and neck cancer xenograft
tumors in nude mice. The addition of low-dose (2 mg/kg)
PLED (P < 0.001) and PLEC (P < 0.001) significantly increased the effect of 4.5 Gy, but not 9 Gy, single-fraction
radiotherapy (SFRT). Both
PLED and PLEC were significantly more effective than their unencapsulated counterparts in increasing the effect of SFRT. In addition,
PLED (P < 0.001) and PLEC (P < 0.05) significantly increased the effect of fractionated
radiotherapy (9 Gy in 3 fractions) in two different dosing schedules (2 mg/kg single dose or three sequential doses of 0.67 mg/kg). Unencapsulated diethylenetriaminepentaacetic
acid and pegylated liposomal diethylenetriaminepentaacetic
acid were used as controls to test the effect of the
liposome vehicle and 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 compared with
radiotherapy alone. This study is the first to demonstrate the value of pegylated
liposomes as vehicles for the delivery of
radiosensitizing drugs in CCRT strategies.