TY - JOUR
T1 - A pilot trial of doxorubicin containing phosphatidyldiglycerol based thermosensitive liposomes in spontaneous feline soft tissue sarcoma
AU - Zimmermann, Katja
AU - Hossann, Martin
AU - Hirschberger, Johannes
AU - Troedson, Karin
AU - Peller, Michael
AU - Schneider, Moritz
AU - Brühschwein, Andreas
AU - Meyer-Lindenberg, Andrea
AU - Wess, Gerhard
AU - Wergin, Melanie
AU - Dörfelt, René
AU - Knösel, Thomas
AU - Schwaiger, Markus
AU - Baumgartner, Christine
AU - Brandl, Johanna
AU - Schwamberger, Sabine
AU - Lindner, Lars H.
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/2/17
Y1 - 2017/2/17
N2 - 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 0.1–0.4 mg/kg DOX (group I), three received 0.4 mg/kg constantly (group II) and three 0.6 mg/kg (group III) IV over 15 min. HT with a target temperature of 41.5 °C was started 15 min before drug application and continued for a total of 60 min. 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 18 F-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.
AB - 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 0.1–0.4 mg/kg DOX (group I), three received 0.4 mg/kg constantly (group II) and three 0.6 mg/kg (group III) IV over 15 min. HT with a target temperature of 41.5 °C was started 15 min before drug application and continued for a total of 60 min. 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 18 F-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.
KW - Hyperthermia
KW - doxorubicin
KW - drug delivery
KW - feline soft tissue sarcoma
KW - phosphatidyldiglycerol
KW - thermosensitive liposomes
UR - http://www.scopus.com/inward/record.url?scp=84991233307&partnerID=8YFLogxK
U2 - 10.1080/02656736.2016.1230233
DO - 10.1080/02656736.2016.1230233
M3 - Article
C2 - 27592502
AN - SCOPUS:84991233307
SN - 0265-6736
VL - 33
SP - 178
EP - 190
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 2
ER -
