The efficacy and hyperthermic release of doxorubicin from liposomal doxorubicin hydrochloride in rabbit VX2 tumours

Abstract

Purpose: To establish optimum conditions for anti-tumour therapy, we evaluated the efficacy of doxorubicin using liposomal doxorubicin and local hyperthermia to improve the anti-tumour efficacy over liposomal doxorubicin alone in rabbit VX2 tumours. Materials and methods: A VX2 tumour model was established in New Zealand white rabbits, which were randomly divided into five groups: 1) control, 2) free doxorubicin hydrochloride (Dox), 3) liposomal doxorubicin hydrochloride (L-Dox), 4) L-Dox plus 41 °C thermotherapy (L-Dox + 41 °C TT); and 5) L-Dox plus 43 °C thermotherapy (L-Dox + 43 °C TT). To achieve complete tumour remission, multiple high-dose administrations (5 mg/kg, once per week for a total of 3 weeks) were given. An ultrasound hyperthermia instrument was used to induce local hyperthermia and the systemic toxicity of Dox was evaluated by changes in weight, blood count and serum lactic dehydrogenase. The anti-tumour effect of Dox was evaluated by observing the gross tumour volume, weight and rabbit survival. Results: The white blood cell count following administration of Dox or L-Dox was lower than for control animals and those treated with L-Dox + 41 °C TT. There was no difference between the groups with regard to the red blood cell count. Compared with the control and Dox groups, tumour proliferation was significantly inhibited following administration of L-Dox, L-Dox + 41 °C TT and L-Dox + 43 °C TT, as evidenced by the difference in tumour volume, weight and survival time. Differences in tumour proliferation were also found between the L-Dox and thermotherapy groups. Conclusion: Local hyperthermia combined with L-Dox can significantly improve anti-tumour efficacy and reduce systemic toxicity.