Comparison of low-temperature-sensitive liposome encapsulated docetaxel and doxorubicin in a murine model of prostate cancer.

Abstract

31 Background: Low-temperature-sensitive liposomes (LTSLs) release their encapsulated drug into targeted tissue when activated by a source of hyperthermia. The efficacy of an LTSL formulation of docetaxel (DOC) or doxorubicin (DOX) was compared against prostate cancer in a xenograft mouse model. Methods: Under an approved IACUC protocol, Luciferase transfected human prostate PC-3M-luciferase cells were inoculated (3x106 cells) subcutaneously in the right hind leg of 8 wk old female athymic nude mice. When tumors reached a volume of 200–300 mm3, mice were randomized to receive one intravenous injection of saline, Stealth liposomal DOX (5 mg/kg), LTSL DOX (5 mg/kg), or LTSL DOC (15 mg/kg), with or without hyperthermia treatment (LTSL DOX and LTSL DOC were supplied by Celsion Corp., Columbia MD). Mice undergoing hyperthermia treatment were anesthetized and stabilized in a holder that allowed for only the leg with tumor to be heated to 41–42°C that triggered LTSL drug release. Mice were monitored daily for tumor volume and body weight. Study end-points included growth of tumor to 5x the initial treatment volume or monitoring of survival for 60 days. Results: The LTSL DOC delayed tumor growth longer (> 14 days) than DOX (0 day) and LTSL DOX (1 day) with hyperthermia (P<0.05). Mice treated with LTSL DOC and hyperthermia survived longest (60 days) compared to all other mice (range 6–8 days, P<0.05). LTSL in the setting of hyperthermia demonstrated complete regression of tumor in 57% of mice. Conclusions: LTSL DOC with hyperthermia delayed tumor growth more than all other treatments. Survival studies suggest LTSL DOC is a more effective temperature sensitive delivery system against PC-3M prostate tumors. No significant financial relationships to disclose.