Response of Canine Mast Cell Tumors to Treatment With Oral Prednisone

McCaw, Dudley L.; Miller, Margaret A.; Ogilvie, Gregory K.; Withrow, Stephen J.; Brewer, William G.; Klein, Mary K.; Bell, Ford W.; Anderson, Sharon K.

doi:10.1111/j.1939-1676.1994.tb03259.x

Cited by 88 publications

(77 citation statements)

References 5 publications

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“…For prognostic evaluation of tumor location, only those dogs with 1 tumor were analyzed (2 responders, 14 nonresponders). Statistical significance was established as P 5 .05.…”

Section: Methodsmentioning

confidence: 99%

Vincristine Therapy for Mast Cell Tumors in Dogs

McCaw

Miller

Bergman

et al. 1997

Veterinary Internal Medicne

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Twenty-seven dogs with naturally occurring mast cell tumors were treated with weekly IV injections of vincristine (0.75 mg/mz) for 4 treatments. Two dogs (7%) had a partial response. Nine dogs (32%) had treatment stopped prematurely because of toxicity or a perceived deterioration in their ast cell tumors (MCTs) are common neoplasms in M dogs, accounting for 7% to 21% of all skin and subcutaneous tumors.' The clinical course of the disease varies from benign to highly malignant, and approximately 50% of MCTs are considered clinically malignant.2 The degree of malignancy can be correlated to the neoplasm's histopathologic appearance, which has led to clinically predictive histopathologic grading system^.'.^ Treatment of MCTs may include surgery, radiotherapy, and chemotherapy.'.' Wide surgical excision is the preferred treatment, and radiation therapy is recommended when complete surgical excision is not possible.'.' Radiotherapy can be used either as a single mode of therapy or in conjunction with surgery. Chemotherapy may be indicated when surgery or radiotherapy is not feasible or as an adjunct to those treatments. Orally administered prednisone produced a response in 5 of 25 (20%) dogs with MCTs treated in a prospective multi-institutional study.5 Most responses were partial (4 of 5 ) and of short duration, with only the 1 complete responder living longer than 7 months5 Anecdotally the vinca alkaloids (vincristine and vinblastine) are reported to reduce tumor size in approximately 30% of the patients.' With objective data lacking, this multi-institutional prospective study was performed to determine if vincristine would reduce the size of clinically measurable canine MCTs. Materials and MethodsThe criteria for inclusion in this study were presence of one or more measurable cutaneous or subcutaneous MCT, histopathology specimen available for review, and no previous treatment with vincristine. Twenty-seven client-owned dogs (with 56 tumors) presented to the participating institutions between August 1991 and March 1995 were evaluated. Fourteen dogs had been previously treated by surgical excision of MCTs but had tumor recurrence at the time of this study (Table 1). Three dogs had been treated with a corticosteroid; 2 of these dogs had also been treated with surgery.Tumor volume was determined before treatment, and the location of the tumors was recorded as trunk, extremities, or head and neck in all dogs. Tumor volume was determined by measuring the tumors in 3 dimensions, then multiplying those values. When multiple tumors were present, all tumors were cytologically diagnosed as MCTs, the volumes were added to calculate the total tumor volume, and the largest tumor was biopsied. Enlarged lymph nodes were cytologically examined. If the lymph node contained mast cells, it was measured and included in total tumor volume. Pretreatment incisional biopsy specimens were obtained in 24 dogs. Three dogs (nos. 4, 10, and 17) had excisional biopsy of the primary tumor and were entered into the study for treatment of lymph...

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“…For prognostic evaluation of tumor location, only those dogs with 1 tumor were analyzed (2 responders, 14 nonresponders). Statistical significance was established as P 5 .05.…”

Section: Methodsmentioning

confidence: 99%

Vincristine Therapy for Mast Cell Tumors in Dogs

McCaw

Miller

Bergman

et al. 1997

Veterinary Internal Medicne

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“…Several studies have evaluated chemotherapy for the treatment of measurable MCT, and response rates from 7% to 78% have been documented [8,10,17,18,23,28]. However, few studies have evaluated the efficacy of chemotherapy as adjuvant treatment for MCT [7,28].…”

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Outcome and Prognostic Factors Following Adjuvant Prednisone/Vinblastine Chemotherapy for High-Risk Canine Mast Cell Tumour: 61 Cases

2006

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ABSTRACT. The medical records of 61 dogs with MCT at high risk for metastasis that were treated with prednisone and VBL following excision +/-radiation therapy were reviewed, and median disease-free interval (DFI), median overall survival time (OS) and prognostic factors assessed. Adverse effects, mostly mild, were noted in 26% of patients, usually after the first VBL dose. 6.5% experienced severe neutropenia. The DFI was 1305 days, and the OS was not reached, with 65% alive at 3 years. 100% of dogs with "high-risk" grade II MCT were alive at 3 years. The OS for dogs with grade III MCT was 1374 days. Histologic grade, location (mucous membrane vs. skin) and use of prophylactic nodal irradiation predicted outcome. Prednisone and VBL chemotherapy is well tolerated, and results in good outcomes following surgery in dogs with MCT at high risk for metastasis. High-grade and mucocutaneous tumors had a worse outcome, and the use of prophylactic nodal irradiation appeared to improve outcome in this group of dogs. KEY WORDS: canine, mastocytoma, Prednisone, vinblastine.J. Vet. Med. Sci. 68(6): 581-587, 2006 Mast cell tumour (MCT) represents the most common malignant cutaneous tumour in the dog [29]. High-grade or undifferentiated MCT (Patnaik grade III) comprise 29 to 40% of all MCT [2,14,22]. In addition to local infiltration, they have a reported metastatic rate of 55 to 96%, and are more likely to result in tumor-related death than are low-or intermediate-grade MCT [29]. While some discordance exists in the literature, patients with MCT of any grade involving the regional lymph node (LN) or arising from a mucous membrane (e.g. gingiva, perineum, prepuce, nailbed) may also be at higher risk for eventual death from MCT [1,10,[28][29][30]. Thus, local therapies alone may be suboptimal for tumour control in these patients.Survival times after surgery alone for high-grade MCT were reported in early studies as 15% at seven months, 6% at 48 months, and a median survival time (MST) of 13 weeks [2,3,22]. More recent studies have reported a MST of approximately 9 months with resection alone in dogs with high-grade MCT [20,25].Several studies have evaluated chemotherapy for the treatment of measurable MCT, and response rates from 7% to 78% have been documented [8,10,17,18,23,28]. However, few studies have evaluated the efficacy of chemotherapy as adjuvant treatment for MCT [7,28].Vinblastine (VBL) is an antimicrotubule alkaloid used in the treatment of hemolymphatic neoplasia in dogs [12], and various human malignancies [24]. We previously reported the results of a study employing prednisone/VBL for the treatment of dogs with gross, microscopic and "high-risk" MCT. An objective response rate of 44% was reported in dogs with gross disease, and there was suggestion that dogs receiving prednisone/VBL following surgery had a favorable clinical outcome compared with historical controls receiving local therapy alone [28]. However, the clinical characteristics of these patients were variable, and a relatively small number were treat...

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“…Chemotherapy (lomustine, vinblastine, cyclophosphomide, prednisone) is used when metastatic disease has been identified, or negative prognostic indicators are present, although no standard of care is currently established (4)(5)(6)(7)(8)(9). Unfortunately, dogs with aggressive MCTs rarely survive beyond 6 months postdiagnosis even after treatment with surgery, chemotherapy, and/or radiation therapy (1).…”

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Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision

London

Malpas

Wood-Follis

et al. 2009

Clinical Cancer Research

344

426

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Purpose: The purpose of this study was to determine the objective response rate (ORR) following treatment of canine mast cell tumors (MCT) with toceranib phosphate (Palladia, SU11654), a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRβ. Secondary objectives were to determine biological response rate, time to tumor progression, duration of objective response, health-related quality of life, and safety of Palladia. Experimental Design: Dogs were randomized to receive oral Palladia 3.25 mg/kg or placebo every other day for 6 weeks in the blinded phase. Thereafter, eligible dogs received open-label Palladia. Results: The blinded phase ORR in Palladia-treated dogs (n = 86) was 37.2% (7 complete response, 25 partial response) versus 7.9% (5 partial response) in placebo-treated dogs (n = 63; P = 0.0004). Of 58 dogs that received Palladia following placebo-escape, 41.4% (8 complete response, 16 partial response) experienced objective response. The ORR for all 145 dogs receiving Palladia was 42.8% (21 complete response, 41 partial response); among the 62 responders, the median duration of objective response and time to tumor progression was 12.0 weeks and 18.1 weeks, respectively. Palladia-treated responders scored higher on health-related quality of life versus Palladia-treated nonresponders (P = 0.030). There was no significant difference in the number of dogs with grade 3/4 (of 4) adverse events; adverse events were generally manageable with dose modification and/or supportive care. Conclusions: Palladia has biological activity against canine MCTs and can be administered on a continuous schedule without need for routine planned treatment breaks. This clinical trial further shows that spontaneous tumors in dogs are good models to evaluate therapeutic index of targeted therapeutics in a clinical setting.

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Response of Canine Mast Cell Tumors to Treatment With Oral Prednisone

Cited by 88 publications

References 5 publications

Vincristine Therapy for Mast Cell Tumors in Dogs

Vincristine Therapy for Mast Cell Tumors in Dogs

Outcome and Prognostic Factors Following Adjuvant Prednisone/Vinblastine Chemotherapy for High-Risk Canine Mast Cell Tumour: 61 Cases

Multi-center, Placebo-controlled, Double-blind, Randomized Study of Oral Toceranib Phosphate (SU11654), a Receptor Tyrosine Kinase Inhibitor, for the Treatment of Dogs with Recurrent (Either Local or Distant) Mast Cell Tumor Following Surgical Excision

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