Pegylated liposome-encapsulated doxorubicin and cisplatin in the treatmentof head and neck xenograft tumours

Purpose: To evaluate the in vitro and in vivo activity of unencapsulated do xorubicin (DOX) and cisplatin (CDDP) and their pegylated liposome encapsula ted counterparts (PLED and PLEC) in a subcutaneous model of human squamous cell cancer of the head and neck. Methods: In vitro cytotoxicity was determ ined by means of the sulphorhodamine B assay and in vivo activity was asses sed in terms of tumour growth delay following single intravenous doses of t he various agents. Treatment-related toxicity was evaluated by means of ser ial weight measurement. Results: The IC50 values for DOX (12.1-fold) and CD DP (21.5-fold) were lower than for their liposome-encapsulated counterparts . When the two unencapsulated agents were compared, the IC50 value for DOX was 16-fold lower than that for CDDP. In the in vivo studies. liposomes con taining DTPA (PLEDTPA) exerted no effect on KB xenograft tumours when compa red to untreated controls (P > 0.1). PLED was significantly more effective than DOX at doses of 2 mg/kg, 4 mg/kg and 8 mg/kg (P < 0.001 for all compar isons). At the 8 mg/kg dose, 7/13 animals treated with PLED were free of di sease at 60 days, compared to 0/12 treated with DOX. PLEC displayed superio r activity in comparison to CDDP at the 4 mg/kg dose level (P < 0.001), alt hough at doses of 2 mg/kg and 10 mg/kg this comparison only reached borderl ine statistical significance(0.1 > P > 0.05). The highest dose level of 20 mg/kg was fatal to all animals in the CDDP group but well-tolerated by the animals in the PLEC group. On the basis of serial weight measurements, both PLED and PLEC were shown to be tolerated better than DOX and CDDP. Conclus ion: Both PLED and PLEC were shown to exert significant activity against he ad and neck xenograft tumours, with PLED showing particular efficacy.