Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs

Sandra M Axiak1, Kim A Selting1, Charles J Decedue2, Carolyn J Henry1,3, Deborah Tate1, Jahna Howell2, K James Bilof1, Dae Y Kim4 1Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA; 2CritiTech Inc, Lawrence, KS, USA; 3Department of Internal Medicine, Division o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Axiak SM, Selting KA, Decedue CJ, Henry CJ, Tate D, Howell J, Bilof KJ, Kim DY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8fc2a7a437dd455b942a4a9d01986cb2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:8fc2a7a437dd455b942a4a9d01986cb2
record_format	dspace
spelling	oai:doaj.org-article:8fc2a7a437dd455b942a4a9d01986cb22021-12-02T02:44:07ZPhase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs1176-91141178-2013https://doaj.org/article/8fc2a7a437dd455b942a4a9d01986cb22011-10-01T00:00:00Zhttp://www.dovepress.com/phase-i-dose-escalation-safety-study-of-nanoparticulate-paclitaxel-cti-a8451https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Sandra M Axiak1, Kim A Selting1, Charles J Decedue2, Carolyn J Henry1,3, Deborah Tate1, Jahna Howell2, K James Bilof1, Dae Y Kim4 1Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA; 2CritiTech Inc, Lawrence, KS, USA; 3Department of Internal Medicine, Division of Hematology and Oncology; 4Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA Background: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Methods: Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m2, and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m2. Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. Results: The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m2. Grade 1&ndash;2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. Conclusion: CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m2. Keywords: paclitaxel, nanoparticle, canineAxiak SMSelting KADecedue CJHenry CJTate DHowell JBilof KJKim DYDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2011, Iss default, Pp 2205-2212 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Axiak SM Selting KA Decedue CJ Henry CJ Tate D Howell J Bilof KJ Kim DY Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
description	Sandra M Axiak1, Kim A Selting1, Charles J Decedue2, Carolyn J Henry1,3, Deborah Tate1, Jahna Howell2, K James Bilof1, Dae Y Kim4 1Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO, USA; 2CritiTech Inc, Lawrence, KS, USA; 3Department of Internal Medicine, Division of Hematology and Oncology; 4Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA Background: Paclitaxel is highly effective in the treatment of many cancers in humans, but cannot be routinely used in dogs as currently formulated due to the exquisite sensitivity of this species to surfactant-solubilizing agents. CTI 52010 is a formulation of nanoparticulate paclitaxel consisting of drug and normal saline. Our objectives were to determine the maximally tolerated dose, dose-limiting toxicities, and pharmacokinetics of CTI 52010 administered intravenously to normal dogs. Methods: Three normal adult hound dogs were evaluated by physical examination, complete blood count, chemistry profile, and urinalysis. Dogs were treated with staggered escalating dosages of CTI 52010 with a 28-day washout. All dogs were treated with a starting dosage of 40 mg/m2, and subsequent dosages were escalated at 50% (dog 1), 100% (dog 2), or 200% (dog 3) with each cycle, to a maximum of 240 mg/m2. Dogs were monitored by daily physical assessment and weekly laboratory evaluation. Standard criteria were used to grade adverse events. Plasma was collected at regular intervals to determine pharmacokinetics. Dogs were euthanized humanely, and necropsy was performed one week after the last treatment. Results: The dose-limiting toxicity was grade 4 neutropenia and the maximum tolerated dosage was 120 mg/m2. Grade 1&ndash;2 gastrointestinal toxicity was noted at higher dosages. Upon post mortem evaluation, no evidence of organ (liver, kidney, spleen) toxicity was noted. Conclusion: CTI 52010 was well tolerated when administered intravenously to normal dogs. A starting dosage for a Phase I/II trial in tumor-bearing dogs is 80 mg/m2. Keywords: paclitaxel, nanoparticle, canine
format	article
author	Axiak SM Selting KA Decedue CJ Henry CJ Tate D Howell J Bilof KJ Kim DY
author_facet	Axiak SM Selting KA Decedue CJ Henry CJ Tate D Howell J Bilof KJ Kim DY
author_sort	Axiak SM
title	Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
title_short	Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
title_full	Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
title_fullStr	Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
title_full_unstemmed	Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs
title_sort	phase i dose escalation safety study of nanoparticulate paclitaxel (cti 52010) in normal dogs
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/8fc2a7a437dd455b942a4a9d01986cb2
work_keys_str_mv	AT axiaksm phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT seltingka phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT deceduecj phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT henrycj phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT tated phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT howellj phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT bilofkj phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs AT kimdy phaseidoseescalationsafetystudyofnanoparticulatepaclitaxelcti52010innormaldogs
_version_	1718402177851981824

Phase I dose escalation safety study of nanoparticulate paclitaxel (CTI 52010) in normal dogs

Ejemplares similares