Efficacy and Toxicity of Paclitaxel (Taxol) for the Treatment of Canine Malignant Tumors

Poirier, Valérie J.; Hershey, Alexander; Burgess, Kristine; Phillips, Brenda; Turek, Michelle; Forrest, Lisa J.; Beaver, L.; Vail, David M.

doi:10.1892/0891-6640(2004)18<219:eatopt>2.0.co;2

Cited by 44 publications

(39 citation statements)

References 11 publications

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“…The toxicity of systemic administration of paclitaxel has been previously determined by Poirier et al in dogs (33). In that study severe myelosuppression was consistently observed in the animals at clinically relevant doses.…”

Section: Discussionmentioning

confidence: 81%

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

et al. 2005

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Introduction: Paclitaxel, a microtubule binding agent with potent anti-glioma activity in vitro, exhibits poor penetrance to the CNS when delivered systemically. To minimize toxicity and reach therapeutic concentrations in the CNS, paclitaxel was previously incorporated into biodegradable microspheres (Paclimer®), and the efficacy of Paclimer® was determined in a rat model of malignant glioma. In this study we report the safety of intracranial Paclimer® in a canine dose escalation toxicity study to prepare its translation into clinical scenarios.

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Section: Discussionmentioning

confidence: 81%

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

et al. 2005

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“…Standard forms of paclitaxel contain ethanol and polyethoxylated castor oil to solubilize it, and dogs are exquisitely sensitive to this formulation. 3,4 Protein-bound paclitaxel, another common form, is a fine particle formulation coated with human serum albumin to increase its water solubility. 5 However, using a foreign protein, such as human albumin in dogs, can also result in a hypersensitivity reaction.…”

Section: Introductionmentioning

confidence: 99%

“…Paclitaxel therapy has been attempted in dogs with spontaneously occurring tumors, and preliminary efficacy was noted with breast and bone cancer. 4 However, toxicity was high; 64% of dogs had hypersensitivity reactions despite heavy pretreatment with diphenhydramine and corticosteroids, and 12% had treatment-related deaths. 4 Yet, preliminary efficacy suggests that this group of drugs would expand our treatment options for dogs if a tolerable formulation existed.…”

Section: Introductionmentioning

confidence: 99%

“…4 However, toxicity was high; 64% of dogs had hypersensitivity reactions despite heavy pretreatment with diphenhydramine and corticosteroids, and 12% had treatment-related deaths. 4 Yet, preliminary efficacy suggests that this group of drugs would expand our treatment options for dogs if a tolerable formulation existed. 4 CTI 52010 has been well tolerated in preclinical rodent models and does not contain substances to which dogs should react.…”

Section: Introductionmentioning

confidence: 99%

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

Axiak¹,

Selting²,

Decedue³

et al. 2011

IJN

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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/m 2 , 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/m 2 . 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/m 2 . Grade 1-2 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/m 2 .

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“…One report describes the induction of partial remissions in 2 dogs with macroscopic mammary tumors after treatment with paclitaxel, but the overall toxicity was high. 22 To the authors' knowledge, docetaxel has not been used for the treatment of tumors in dogs. The dose of 30 mg/m used in this study was derived from preclinical studies in Beagle dogs.…”

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confidence: 99%

Postoperative Adjuvant Treatment of Invasive Malignant Mammary Gland Tumors in Dogs with Doxorubicin and Docetaxel

Simón

Schoenrock

Baumgärtner

et al. 2006

Veterinary Internal Medicne

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Background: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors.Hypothesis: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs.Animals: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used.Methods: A prospective clinical trial in which dogs were treated with surgery alone (n 5 19) or also received adjuvant chemotherapy (n 5 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m 2 preceded by dexamethasone and diphenhydramine administration. Results: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P 5 .17), time to metastasis (P 5 .71), and overall survival (P 5 .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P 5 .009) and tumor fixation to underlying structures (P 5 .043, time to metastasis), as well as age (P 5 .018) and histologic stage (P , .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment.Conclusions and Clinical Importance: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.

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Efficacy and Toxicity of Paclitaxel (Taxol) for the Treatment of Canine Malignant Tumors

Cited by 44 publications

References 11 publications

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

Local Intracerebral Administration of Paclitaxel with the Paclimer® Delivery System: Toxicity Study in a Canine Model

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

Postoperative Adjuvant Treatment of Invasive Malignant Mammary Gland Tumors in Dogs with Doxorubicin and Docetaxel

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