Neoadjuvant therapy of locally advanced feline injection site sarcoma with thermosensitive doxorubicin-containing phosphatidyldiglycerol liposomes or free doxorubicin in combination with regional hyperthermia
17 February 2020 (online)
Background Feline injection-site sarcoma (FISS) is a locally advance tumor that requires a multimodality therapy. FISS shows a low response to doxorubicin (DOX). This could be improved with DOX-loaded phosphatidyldiglycerol-based thermosensitive liposomes (DPPG2-TSLs) and regional hyperthermia (RHT).
Hypothesis/objectives DPPG2-TSL-DOX and RHT leads to improved treatment response than DOX and RHT.
Animals Eight cats were included; 4 cats were treated with 1 mg/kg DPPG2-TSL-DOX and 4 cats were treated with 1 mg/kg DOX, both in combination with RHT.
Methods After complete staging including PET-MRI, 6 treatment cycles with DPPG2-TSL-DOX or DOX in combination with RHT were applied q 2 weeks. Treatment response was monitored via calliper and PET-MRI measurements. RHT with a target temperature of 41.5°C was started 15 minutes before i. v. drug administration and continued for a total of 60 minutes.
Results Treatment was feasible and no dose-limiting toxicity was observed. All cats treated with DPPG2-TSL-DOX showed a response to treatment whereas only one cat treated with free DOX responded to treatment.
Conclusions The neoadjuvant treatment with DPPG2-TSL-DOX and RHT was well tolerated and effective. Response to treatment with DPPG2-TSL-DOX suggests overcoming drug resistance mechanism by a more effective drug delivery. This treatment combination exhibits a great potential for the treatment of advanced stage FISS.