A pilot trial of doxorubicin containing phosphatidyldiglycerol based thermosensitive liposomes in spontaneous feline soft tissue sarcoma

Zimmermann, Katja; Hossann, Martin; Hirschberger, Johannes; Trödson, Karin; Peller, Michäl; Schneider, Moritz; Brühschwein, Andreas ; Meyer-Lindenberg, Andrea; Wess, Gerhard; Wergin, Melanie; Dörfelt, Rene; Knösel, Thomas; Schwaiger, Markus; Baumgartner, Christine; Brandl, Johanna; Schwamberger, Sabine und Lindner, Lars H. (2017): A pilot trial of doxorubicin containing phosphatidyldiglycerol based thermosensitive liposomes in spontaneous feline soft tissue sarcoma. In: International Journal of Hyperthermia, Bd. 33, Nr. 2: S. 178-190

Abstract

Purpose: Doxorubicin (DOX)-loaded phosphatidyldiglycerol-based thermosensitive liposomes (DPPG(2)-TSL-DOX) combined with local hyperthermia (HT) was evaluated in cats with locally advanced spontaneous fibrosarcomas (soft tissue sarcoma [STS]). The study was designed to evaluate the safety and pharmacokinetic profile of the drug. Results from four dose-levels are reported.Methods: Eleven client-owned cats with advanced STS were enrolled. Five cats received escalating doses of 0.1-0.4mg/kg DOX (group I), three received 0.4mg/kg constantly (group II) and three 0.6mg/kg (group III) IV over 15min. HT with a target temperature of 41.5 degrees C was started 15min before drug application and continued for a total of 60min. Six HT treatments were applied every other week using a radiofrequency applicator. Tumour growth was monitored by magnetic resonance imaging (MRI) and for dose level III also with F-18-FDG PET.Results: Treatment was generally well tolerated and reasons for premature study termination in four cats were not associated with drug-induced toxicity. No DPPG(2)-TSL-DOX based hypersensitivity reaction was observed. One cat showed simultaneous partial response (PR) in MRI and positron emission tomography (PET) whereas one cat showed stable disease in MRI and PR in PET (both cats in dose level III). Pharmacokinetic measurements demonstrated DOX release triggered by HT.Conclusion: DPPG(2)-TSL-DOX+HT is a promising treatment option for advanced feline STS by means of targeted drug delivery. As MTD was not reached further investigation is warranted to determine if higher doses would result in even better tumour responses.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Tiermedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0265-6736
• Sprache: Englisch