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A dose-escalation study of combretastatin A4-phosphate in healthy dogs

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Abstract
Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100mgm(-2). At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100mgm(-2) additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100mgm(-2), low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75mgm(-2) seem to be well tolerated. The severity of the neurotoxicity observed at 100mgm(-2), although transient, does not invite to use this dose in canine oncology patients.
Keywords
anticancer therapy, combretastatin A4-phosphate, dogs, dose-escalation, vascular disrupting agent, VASCULAR-TARGETING AGENT, ANAPLASTIC THYROID-CARCINOMA, PHASE-I, A4 PHOSPHATE, A-4 PHOSPHATE, CANCER THERAPEUTICS, ANGIOGENIC SWITCH, EFFICACY, TRIAL, MAROPITANT

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MLA
Abma, Eline, et al. “A Dose-Escalation Study of Combretastatin A4-Phosphate in Healthy Dogs.” VETERINARY AND COMPARATIVE ONCOLOGY, vol. 16, no. 1, 2018, pp. E16–22, doi:10.1111/vco.12327.
APA
Abma, E., Smets, P., Daminet, S., Cornelis, I., De Clercq, K., Ni, Y., … De Rooster, H. (2018). A dose-escalation study of combretastatin A4-phosphate in healthy dogs. VETERINARY AND COMPARATIVE ONCOLOGY, 16(1), E16–E22. https://doi.org/10.1111/vco.12327
Chicago author-date
Abma, Eline, Pascale Smets, Sylvie Daminet, Ine Cornelis, Kaat De Clercq, Y Ni, Lise Vlerick, and Hilde De Rooster. 2018. “A Dose-Escalation Study of Combretastatin A4-Phosphate in Healthy Dogs.” VETERINARY AND COMPARATIVE ONCOLOGY 16 (1): E16–22. https://doi.org/10.1111/vco.12327.
Chicago author-date (all authors)
Abma, Eline, Pascale Smets, Sylvie Daminet, Ine Cornelis, Kaat De Clercq, Y Ni, Lise Vlerick, and Hilde De Rooster. 2018. “A Dose-Escalation Study of Combretastatin A4-Phosphate in Healthy Dogs.” VETERINARY AND COMPARATIVE ONCOLOGY 16 (1): E16–E22. doi:10.1111/vco.12327.
Vancouver
1.
Abma E, Smets P, Daminet S, Cornelis I, De Clercq K, Ni Y, et al. A dose-escalation study of combretastatin A4-phosphate in healthy dogs. VETERINARY AND COMPARATIVE ONCOLOGY. 2018;16(1):E16–22.
IEEE
[1]
E. Abma et al., “A dose-escalation study of combretastatin A4-phosphate in healthy dogs,” VETERINARY AND COMPARATIVE ONCOLOGY, vol. 16, no. 1, pp. E16–E22, 2018.
@article{8531514,
  abstract     = {{Combretastatin A4-Phosphate (CA4P) is a vascular disrupting agent revealing promising results in cancer treatments for humans. The aim of this study was to investigate the safety and adverse events of CA4P in healthy dogs as a prerequisite to application of CA4P in dogs with cancer. Ten healthy dogs were included. The effects of escalating doses of CA4P on physical, haematological and biochemical parameters, systolic arterial blood pressure, electrocardiogram, echocardiographic variables and general wellbeing were characterised. Three different doses were tested: 50, 75 and 100mgm(-2). At all 3 CA4P doses, nausea, abdominal discomfort as well as diarrhoea were observed for several hours following administration. Likewise, a low-grade neutropenia was observed in all dogs. Doses of 75 and 100mgm(-2) additionally induced vomiting and elevation of serum cardiac troponine I levels. At 100mgm(-2), low-grade hypertension and high-grade neurotoxicity were also observed. In healthy dogs, doses up to 75mgm(-2) seem to be well tolerated. The severity of the neurotoxicity observed at 100mgm(-2), although transient, does not invite to use this dose in canine oncology patients.}},
  author       = {{Abma, Eline and Smets, Pascale and Daminet, Sylvie and Cornelis, Ine and De Clercq, Kaat and Ni, Y and Vlerick, Lise and De Rooster, Hilde}},
  issn         = {{1476-5810}},
  journal      = {{VETERINARY AND COMPARATIVE ONCOLOGY}},
  keywords     = {{anticancer therapy,combretastatin A4-phosphate,dogs,dose-escalation,vascular disrupting agent,VASCULAR-TARGETING AGENT,ANAPLASTIC THYROID-CARCINOMA,PHASE-I,A4 PHOSPHATE,A-4 PHOSPHATE,CANCER THERAPEUTICS,ANGIOGENIC SWITCH,EFFICACY,TRIAL,MAROPITANT}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{E16--E22}},
  title        = {{A dose-escalation study of combretastatin A4-phosphate in healthy dogs}},
  url          = {{http://doi.org/10.1111/vco.12327}},
  volume       = {{16}},
  year         = {{2018}},
}

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