ABSTRACT
The purpose of this retrospective study was to determine the efficacy and toxicity of a combined protocol of vinblastine, cyclophosphamide and prednisone (VCP) in 35 dogs with mast cell tumours (MCTs). Eleven dogs had measurable disease (group 1) and 24 dogs had incompletely excised MCT or were at high risk for metastasis (group 2). Five patients in group 1 achieved complete response, two partial responses, two stable diseases and two progressive diseases. The median progression-free survival time (PFST) for group 1 and 2 dogs was 74 and 865 days, respectively. The median overall survival time (OST) for group 1 and 2 dogs was 145 and >2092 days, respectively. Significant negative multivariate prognostic factors included macroscopic disease and reduced vinblastine (VBL) treatments for PFST, and presence of MCT in bone marrow analysis, Patnaik grade III MCT and reduced VBL treatments for OST. Toxicity was infrequent and self-limiting. This study suggests that the VCP protocol should be considered as an option in the treatment of MCT in dogs.
ABSTRACT
INTRODUCTION: Canine malignant melanoma (CMM) is an aggressive neoplasm treated with surgery and/or fractionated RT; however, metastatic disease is common and chemoresistant. Preclinical and clinical studies by our laboratory and others have shown that xenogeneic DNA vaccination with tyrosinase family members can produce immune responses resulting in tumor rejection or protection and prolongation of survival. These studies provided the impetus for development of a xenogeneic DNA vaccine program in CMM. MATERIALS AND METHODS: Cohorts of three dogs each received increasing doses of xenogeneic plasmid DNA encoding either human tyrosinase (huTyr; 100/500/1500 mcg), murine GP75 (muGP75; 100/500/1500 mcg), murine tyrosinase (muTyr; 5 dogs each at 100/500 mcg), muTyr+/-HuGM-CSF (9 dogs at 50 mcg muTyr, 3 dogs each at 100/400/800 mcg HuGM-CSF, or 3 dogs each at 50 mcg muTyr with 100/400/800 mcg HuGM-CSF), or 50 mcg MuTyr intramuscularly biweekly for a total of four vaccinations. RESULTS: The Kaplan-Meier median survival time (KM MST) for all stage II-IV dogs treated with huTyr, muGP75 and muTyr are 389, 153 and 224 days, respectively. Preliminarily, the KM MST for stage II-IV dogs treated with 50 mcg MuTyr, 100/400/800 mcg HuGM-CSF or combination MuTyr/HuGM-CSF are 242, 148 and >402 (median not reached) days, respectively. Thirty-three stage II-III dogs with loco-regionally controlled CMM across the xenogeneic vaccine studies have a KM MST of 569 days. Minimal to mild pain was noted on vaccination and one dog experienced vitiligo. We have recently investigated antibody responses in dogs vaccinated with HuTyr and found 2- to 5-fold increases in circulating antibodies to human tyrosinase. CONCLUSIONS: The results of these trials demonstrate that xenogeneic DNA vaccination in CMM: (1) is safe, (2) leads to the development of anti-tyrosinase antibodies, (3) is potentially therapeutic, and (4) is an attractive candidate for further evaluation in an adjuvant, minimal residual disease Phase II setting for CMM.
Subject(s)
Dog Diseases/therapy , Melanoma/veterinary , Vaccines, DNA/therapeutic use , Animals , Antibody Formation , Dogs , Enzyme-Linked Immunosorbent Assay , Melanoma/therapy , Monophenol Monooxygenase/immunologyABSTRACT
Abstract Carcinomatosis, sarcomatosis and mesothelioma, with or without malignant effusions, are difficult to treat and generally carry a poor prognosis. The purpose of this study was two-fold; first, to determine the prognosis for dogs with carcinomatosis, sarcomatosis, or mesothelioma, with or without malignant effusions; second, to evaluate the safety and efficacy of treatment with intracavitary (IC) carboplatin and mitoxantrone in dogs with these syndromes. Nineteen dogs were evaluated. Seven were untreated and 12 were treated with IC chemotherapy (mitoxantrone and/or carboplatin), and multiple factors were analysed for significance with respect to survival time. The median survival time (MST) for untreated dogs was 25 days, whereas the MST for treated dogs was 332 days (Log Rank, P < 0.0001). Treatment with IC chemotherapy was well tolerated. This study suggests that IC chemotherapy with mitoxantrone and/or carboplatin is an effective treatment for dogs with carcinomatosis, sarcomatosis or mesothelioma, with or without malignant effusion.
