Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014–2017)

Musser, Margaret; Taikowski, Kathryn; Johannes, Chad M.; Bergman, Philip J.

doi:10.1186/s12917-018-1597-7

Cited by 22 publications

(37 citation statements)

References 40 publications

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“…Although a necropsy was not performed, it is possible that this patient experienced a treatment-associated grade 5 gastrointestinal AE. This case highlights the fact that, while most dogs have only mild to moderate AEs associated with toceranib, it is not without risk [16][17][18][19][20][21][22][23][24][25][26][27]33]. Given that earlier studies evaluating toceranib doses of 2.5 to 3.5 mg/kg found no differences in biologic activity observed at higher doses, it may be reasonable to administer toceranib at a dose between 2.4 and 3.0 mg/kg to avoid severe gastrointestinal toxicity and frequent drug holidays when treating dogs with insulinoma [32,34].…”

Section: Discussionmentioning

confidence: 80%

“…Moreover, in the initial phase I study for toceranib, as well as subsequent off-label investigations of toceranib, clinical responses were observed in dogs with a spectrum of solid tumour types [18][19][20][21][22][23][24][25][26][27]. More recently, a case report described a dog diagnosed with metastatic insulinoma experiencing long-term glycemic control with toceranib [28].…”

Section: Introductionmentioning

confidence: 99%

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WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).

Sheppard‐Olivares

Bello

Johannes

et al. 2020

Preprint

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BACKGROUND: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These are malignant tumours with a high metastatic rate and limited efficacious chemotherapeutic options available. Recent literature supports the use of the multi-receptor tyrosine kinase inhibitor sunitinib malate for treatment of metastatic insulinoma in people. Toceranib phosphate is a veterinary targeted therapy that may provide benefit in treatment of canine insulinomas. The primary objectives of this study were to describe the duration of clinical benefit, defined as absence of clinical signs associated with hypoglycemia and/or measurable response according to the response evaluation criteria for solid tumours in dogs (cRECIST), and measures of outcome, namely progression free interval (PFI) and overall survival time (OST) in dogs diagnosed with insulinoma treated with toceranib. A secondary objective was to describe the adverse effects of toceranib in dogs with insulinoma.RESULTS: A medical record search identified 30 dogs diagnosed with insulinoma and treated with toceranib at five university hospitals and eight veterinary specialty referral hospitals. A majority (66.7%) of dogs with measurable disease experienced either complete response (CR), partial response (PR), or stable disease (SD) with toceranib therapy. The overall median progression free interval (PFI) was 561 days (95% confidence interval: [246, 727 days]). The overall median survival time (OST) was 656 days [310, 1045 days]. Larger dogs were at increased risk for disease progression (P = 0.0310) and death (P = 0.0064), with every 1 kg increase in body weight resulting in hazard ratios (HRs) of 1.045 [1.003, 1.084] and 1.05 [1.012, 1.090], respectively. In addition, time to disease progression was associated with use of therapies prior to toceranib (P = 0.0050) and type of veterinary practice (P = 0.0025). The most common adverse events with toceranib therapy were grade 1 or 2 gastrointestinal toxicities.CONCLUSIONS: Clinical benefit was reported in the majority of dogs diagnosed with insulinoma treated with toceranib, but randomized, prospective studies are needed to assess and quantify the effect of this therapy. The most commonly observed adverse events (AEs) were gastrointestinal AEs.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).

Sheppard‐Olivares

Bello

Johannes

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Given these agents are not directly cytotoxic, an end result of disease stabilization rather than tumour regression is common. Toceranib has been proven effective in treating numerous neuroendocrine tumours in dogs including insulinomas, pheochromocytomas, and thyroid carcinomas . For many of these tumour types, disease stabilization with toceranib is a common endpoint and this is particularly true when used in an advanced disease setting.…”

Section: Discussionmentioning

confidence: 99%

Retrospective evaluation of canine heart base tumours treated with toceranib phosphate (Palladia): 2011‐2018

Lew

McQuown

Borrego³

et al. 2019

Vet Comparative Oncology

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Heart base tumours (HBT) occur commonly in older, brachycephalic dogs. A presumptive diagnosis is made based on location and appearance of the tumour via echocardiogram. Effective treatment options are limited to surgery (when feasible) or radiation therapy. Benefit of medical management is presently unknown. The goal of this retrospective study was to assess the efficacy and tolerability of toceranib phosphate for dogs with HBT. Twenty-eight dogs with histologically, cytologically confirmed or presumed HBT were evaluated retrospectively. Twenty-seven dogs were treated with single agent toceranib. One dog received combination therapy with concurrent metronomic chemotherapy. This dog was not included in response or survival analysis.Factors assessed included clinical signs, hematologic/biochemical parameters and response to treatment. For the 27 dogs receiving single agent toceranib, an overall response rate of 10% was found. Overall median survival time was 823 days (range, 68-1190 days). The overall response rate for the dogs presenting with metastasis was 28.5%, with a median survival time of 532 days (range, 77-679 days). This was not significantly different than the median survival time of 796 days for dogs who did not present with metastasis. Of the dogs displaying clinical signs at the time of diagnosis, 90% had improvement and 81% had complete resolution of signs after starting toceranib. Toxicity was seen in 54% of dogs with gastrointestinal distress as the most common toxicity but dose reductions were infrequent required. Results demonstrate that toceranib phosphate is a well-tolerated and effective treatment for inoperable canine heart base tumours including dogs with advanced or metastatic disease. K E Y W O R D S canine, chemodectoma, heart base tumour, Palladia, toceranib phosphate

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“…Toceranib phosphate (Palladia®; Zoetis Animal Heath, Madison, NJ, USA) is a small molecule inhibitor with similar molecular targets to sunitinib, some of which have been identi ed in two canine tumours of neuroendocrine histology [23][24][25]. Moreover, in the initial phase I study for toceranib, as well as subsequent off-label investigations of toceranib, clinical responses were observed in dogs with a spectrum of solid tumour types [26][27][28][29][30][31][32][33][34][35][36]. More recently, a case report described a dog diagnosed with metastatic insulinoma experiencing long-term glycemic control with toceranib [37].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019)

Sheppard‐Olivares¹,

Bello²,

Johannes³

et al. 2020

Preprint

View full text Add to dashboard Cite

BACKGROUNDInsulinomas are the most common tumour of the endocrine pancreas in dogs. These are malignant tumours with a high metastatic rate and limited efficacious chemotherapeutic options available. Recent literature supports the use of the multi-receptor tyrosine kinase inhibitor sunitinib malate for treatment of metastatic insulinoma in people. Toceranib phosphate is a veterinary targeted therapy that may provide benefit in treatment of canine insulinomas. The primary objectives of this retrospective study were to describe the control of clinical signs, response to toceranib in the case of measurable disease, and outcomes of toceranib therapy for canine insulinoma. A secondary objective was to describe the adverse effects of toceranib in dogs with insulinoma.RESULTSA medical record search identified 30 dogs diagnosed with insulinoma and treated with toceranib at five university hospitals and eight veterinary specialty referral hospitals. A majority (66.7%) of dogs with measurable disease experienced either complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 10 weeks with toceranib therapy. The overall median progression free interval (PFI) was 561 days (95% confidence interval: [246, 727 days]). The overall medial survival time (OST) was 656 days [310, 1045 days]. Larger dogs were at increased risk for disease progression (P = 0.0310) and death (P = 0.0064), with every 1 kg increase in body weight resulting in hazard ratios (HRs) of 1.045 [1.003, 1.084] and 1.05 [1.012, 1.090], respectively. In addition, time to disease progression was associated with use of therapies prior to toceranib (P = 0.0050) and type of veterinary practice (P = 0.0025). The most common adverse events with toceranib therapy were grade 1 or 2 gastrointestinal toxicities.CONCLUSIONSClinical benefit was reported in the majority of dogs diagnosed with insulinoma treated with toceranib, but randomized, prospective studies are needed to assess and quantify the effect of this therapy. The most commonly observed adverse events (AEs) were grade 1 or 2 gastrointestinal AEs.

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Retrospective evaluation of toceranib phosphate (Palladia®) use in the treatment of inoperable, metastatic, or recurrent canine pheochromocytomas: 5 dogs (2014–2017)

Cited by 22 publications

References 40 publications

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019).

Retrospective evaluation of canine heart base tumours treated with toceranib phosphate (Palladia): 2011‐2018

WITHDRAWN: Management of canine insulinomas with toceranib phosphate: 30 cases (2009-2019)

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