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1.
Vet Pathol ; 58(5): 858-863, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33888024

RESUMO

One of the primary objectives of the Oncology Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects and provide guidelines for oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for grading of canine cutaneous mast cell tumors, suggest guidelines for reporting, and provide recommendations for its clinical interpretation. The article mainly focuses on histologic grading, but relevant information on mitotic count and cytological grading are also discussed. This document represents the opinions of the working group and the authors but does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.


Assuntos
Doenças do Cão , Neoplasias , Animais , Consenso , Doenças do Cão/diagnóstico , Cães , Humanos , Mastócitos , Neoplasias/veterinária , Patologistas
2.
Can Vet J ; 62(2): 133-140, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33542551

RESUMO

The objective of this retrospective study was to evaluate the effects of surgery on outcome for dogs with naturally occurring urinary bladder transitional cell carcinoma. Forty-seven dogs met the inclusion criteria. Thirty-one dogs (Group A) were treated with partial cystectomy and adjunctive medical therapy and 16 dogs (Group B) were treated with medical therapy alone. Overall survival was greater in dogs treated with partial cystectomy and adjunctive medical therapy (498 days for Group A versus 335 days for Group B, hazard ratio 2.5; 95% confidence interval: 1.1 to 5.7; P = 0.026). Progression-free survival was not different between groups (85 days for Group A versus 83 days for Group B; P = 0.663). No prognostic factors were identified for progression-free survival. Due to the many cases in Group A that were lost to follow-up, time-to-event survival analysis was performed. No significant difference in overall survival was noted, and no prognostic factors were identified in the time-to-event analysis. Prospective, randomized studies are needed to determine the role of partial cystectomy in the treatment of transitional cell carcinoma.


Résultats cliniques des chiens atteints d'un carcinome à cellules transitionnelles recevant un traitement médical, avec et sans cystectomie partielle. L'objectif de cette étude rétrospective était d'évaluer les effets de la chirurgie sur les résultats chez des chiens atteints d'un carcinome à cellules transitionnelles de la vessie d'origine naturelle. Quarante-sept chiens répondaient aux critères d'inclusion. Trente et un chiens (Groupe A) ont été traités par cystectomie partielle et traitement médical d'appoint et 16 chiens (Groupe B) ont été traités par thérapie médicale seule. La survie globale était plus élevée chez les chiens traités par cystectomie partielle et traitement médical d'appoint (498 jours pour le Groupe A contre 335 jours pour le Groupe B, rapport de risque de 2,5; intervalle de confiance à 95 % : 1,1 à 5,7; P = 0,026). La survie sans progression n'était pas différente entre les groupes (85 jours pour le Groupe A contre 83 jours pour le Groupe B; P = 0,663). Aucun facteur pronostique n'a été identifié pour la survie sans progression. En raison des nombreux cas dans le Groupe A qui ont été perdus de vue lors du suivi, une analyse du temps de survie a été realisée. Aucune différence significative dans la survie globale n'a été notée et aucun facteur pronostique n'a été identifié dans l'analyse du temps de survive. Des études prospectives randomisées sont nécessaires pour déterminer le rôle de la cystectomie partielle dans le traitement du carcinome à cellules transitionnelles.(Traduit par Dr Serge Messier).


Assuntos
Carcinoma de Células de Transição , Doenças do Cão , Neoplasias da Bexiga Urinária , Animais , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/cirurgia , Carcinoma de Células de Transição/veterinária , Cistectomia/veterinária , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Cães , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/veterinária
3.
BMC Vet Res ; 11: 131, 2015 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-26062540

RESUMO

BACKGROUND: Spenic hemangiosarcoma (HSA) in dogs treated with surgery alone is associated with short survival times, and the addition of doxorubicin (DOX) chemotherapy only modestly improves outcome. The purpose of this study was to evaluate the impact of toceranib administration on progression free survival in dogs with stage I or II HSA following splenectomy and single agent DOX chemotherapy. We hypothesized that dogs with splenic HSA treated with adjuvant DOX followed by toceranib would have prolonged disease-free interval (DFI) and overall survival time (OS) when compared to historical dogs treated with DOX-based chemotherapy alone. RESULTS: Dogs with stage I or II splenic HSA were administered 5 cycles of single-agent DOX every 2 weeks beginning within 14 days of splenectomy. Dogs were restaged 2 weeks after completing DOX, and those without evidence of metastatic disease began toceranib therapy at 3.25 mg/kg every other day. Forty-three dogs were enrolled in this clinical trial. Seven dogs had evidence of metastatic disease either before or at re-staging, and an additional 3 dogs were found to have metastatic disease within 1 week of toceranib administration. Therefore 31 dogs went on to receive toceranib following completion of doxorubicin treatment. Twenty-five dogs that received toceranib developed metastatic disease. The median disease free interval for all dogs enrolled in this study (n = 43) was 138 days, and the median disease free interval for those dogs that went on to receive toceranib (n = 31) was 161 days. The median survival time for all dogs enrolled in this study was 169 days, and the median survival time for those dogs that went on to receive toceranib was 172 days. CONCLUSIONS: The use of toceranib following DOX chemotherapy does not improve either disease free interval or overall survival in dogs with stage I or II HSA.


Assuntos
Doenças do Cão/tratamento farmacológico , Doxorrubicina/uso terapêutico , Hemangiossarcoma/veterinária , Indóis/uso terapêutico , Pirróis/uso terapêutico , Neoplasias Esplênicas/veterinária , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Cães , Feminino , Hemangiossarcoma/tratamento farmacológico , Indóis/administração & dosagem , Masculino , Pirróis/administração & dosagem , Neoplasias Esplênicas/tratamento farmacológico
4.
J Foot Ankle Surg ; 54(2): 188-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25116232

RESUMO

The purpose of the present study was to compare the primary bending stiffness characteristics of 5 different ankle arthrodesis fixation techniques: 3 compression screws, an anterior locking plate, a lateral locking plate, an anterior locking plate with a compression screw, and a lateral locking plate with a compression screw. A total of 25 full-scale anatomic models consisting of fourth-generation composite tibiae and tali were tested using an Instron 4505 Universal Testing System. We hypothesized that the use of a compression screw with a locking plate would add considerable stiffness to the fixation construct compared with the use of a locking plate alone. The data have shown that an anterior or lateral plate with a compression screw provides significantly greater stiffness than both a plate and 3 compression screws used individually. No significant difference was seen between the anterior plate with a compression screw and the lateral plate with a compression screw. No significant differences were found among the use of an anterior plate, a lateral plate, or 3 compression screws. We have concluded that when using a locking plate in an anterior or lateral configuration, the addition of a compression screw will considerably increase the primary bending stiffness of ankle arthrodesis.


Assuntos
Articulação do Tornozelo/fisiopatologia , Articulação do Tornozelo/cirurgia , Artrodese/instrumentação , Fixadores Internos , Artrodese/métodos , Humanos , Modelos Anatômicos , Amplitude de Movimento Articular/fisiologia , Suporte de Carga/fisiologia
5.
Vet Clin North Am Small Anim Pract ; 54(3): 469-476, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38184436

RESUMO

The expanding number of specialized oncology therapeutics available in veterinary oncology can make staying updated on the most recent advances challenging. This article summarizes the mechanism of action, available supporting data, and clinical use of three key veterinary cancer/supportive care therapeutics: Laverdia-CA1, Canalevia-CA1, and Stelfonta. This information will help guide clinical use within your practice and can be incorporated into discussions with clients regarding the newest available options for their dogs with cancer.


Assuntos
Doenças do Cão , Neoplasias , Humanos , Animais , Cães , Neoplasias/terapia , Neoplasias/veterinária , Oncologia , Doenças do Cão/terapia
6.
Front Vet Sci ; 11: 1359426, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645640

RESUMO

Melanoma of the dog and cat poses a clinical challenge to veterinary practitioners across the globe. As knowledge evolves, so too do clinical practices. However, there remain uncertainties and controversies. There is value for the veterinary community at large in the generation of a contemporary wide-ranging guideline document. The aim of this project was therefore to assimilate the available published knowledge into a single accessible referenced resource and to provide expert clinical guidance to support professional colleagues as they navigate current melanoma challenges and controversies. Melanocytic tumors are common in dogs but rare in cats. The history and clinical signs relate to the anatomic site of the melanoma. Oral and subungual malignant melanomas are the most common malignant types in dogs. While many melanocytic tumors are heavily pigmented, making diagnosis relatively straightforward, melanin pigmentation is variable. A validated clinical stage scheme has been defined for canine oral melanoma. For all other locations and for feline melanoma, TNM-based staging applies. Certain histological characteristics have been shown to bear prognostic significance and can thus prove instructive in clinical decision making. Surgical resection using wide margins is currently the mainstay of therapy for the local control of melanomas, regardless of primary location. Radiotherapy forms an integral part of the management of canine oral melanomas, both as a primary and an adjuvant therapy. Adjuvant immunotherapy or chemotherapy is offered to patients at high risk of developing distant metastasis. Location is the major prognostic factor, although it is not completely predictive of local invasiveness and metastatic potential. There are no specific guidelines regarding referral considerations for dogs with melanoma, as this is likely based on a multitude of factors. The ultimate goal is to provide the best options for patients to extend quality of life and survival, either within the primary care or referral hospital setting.

8.
Nano Lett ; 12(8): 4254-9, 2012 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-22746330

RESUMO

Safe and effective vaccines offer the best intervention for disease control. One strategy to maximize vaccine immunogenicity without compromising safety is to rationally design molecular complexes that mimic the natural structure of immunogenic microbes but without the disease-causing components. Here we use highly programmable DNA nanostructures as platforms to assemble a model antigen and CpG adjuvants together into nanoscale complexes with precise control of the valency and spatial arrangement of each element. Our results from immunized mice show that compared to a mixture of antigen and CpG molecules, the assembled antigen-adjuvant-DNA complexes induce strong and long-lasting antibody responses against the antigen without stimulating a reaction to the DNA nanostructure itself. This result demonstrates the potential of DNA nanostructures to serve as general platforms for the rational design and construction of a variety of vaccines.


Assuntos
DNA/química , Nanoestruturas/química , Vacinas Sintéticas/química , Animais , Reações Antígeno-Anticorpo , Linfócitos B/imunologia , Linhagem Celular , DNA/imunologia , Células Dendríticas , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T/imunologia , Vacinas Sintéticas/imunologia
9.
Can Vet J ; 54(3): 237-42, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23997259

RESUMO

Canine hemangiosarcoma (HSA) is a highly malignant tumor for which standard chemotherapy has done little to substantially improve survival. Cyclooxygenase-2 (Cox-2) plays a role in the formation, growth, and metastasis of tumors and inhibitors have demonstrated therapeutic benefit with certain canine cancers. In this prospective study, 21 dogs received adjuvant therapy combining the selective Cox-2 inhibitor deracoxib with doxorubicin, following splenectomy for HSA. The combination was well-tolerated with only low-grade gastrointestinal and hematologic toxicities noted. An overall median survival of 150 days (range; 21 to 1506 days) was noted. Although there was no significant difference in survival based upon stage of disease, dogs with stage III HSA (n = 11) had a median survival of 149 days, which appears to be longer than previously reported. Further studies are warranted to evaluate the potential benefit of Cox-2 inhibitors in the treatment of canine HSA.


Traitement adjuvant à la doxorubicine et au déracoxib pour l'angiosarcome splénique canin : étude pilote. L'angiosarcome canin est une tumeur hautement maligne pour laquelle la chimiothérapie standard a peu fait pour améliorer substantiellement la survie. La cyclooxygénase-2 (Cox-2) joue un rôle dans la formation, la croissance et la métastase des tumeurs et des inhibiteurs ont démontré des bienfaits thérapeutiques pour certains cancers canins. Dans cette étude prospective, 21 chiens ont reçu un traitement adjuvant combinant l'inhibiteur de la Cox-2 sélectif déracoxib avec la doxorubicine, après la splénectomie pour l'angiosarcome. La combinaison a été bien tolérée et seulement des toxicités gastro-intestinales et hématologiques de faible intensité ont été signalées. Une survie médiane globale de 150 jours (écart de 21 à 1506 jours) a été signalée. Même s'il n'y a pas eu de différence significative dans la survie si l'on se base sur le stade de la maladie, les chiens avec un angiosarcome de stade III (n = 11) ont eu une survie médiane de 149 jours, ce qui semble plus long que ce qui avait déjà été signalé. De nouvelles études sont justifiées afin d'évaluer le bienfait potentiel des inhibiteurs de la Cox-2 pour le traitement de l'angiosarcome canin.(Traduit par Isabelle Vallières).


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Doxorrubicina/uso terapêutico , Hemangiossarcoma/veterinária , Neoplasias Esplênicas/veterinária , Sulfonamidas/uso terapêutico , Animais , Antibióticos Antineoplásicos/administração & dosagem , Quimioterapia Adjuvante/veterinária , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Cães , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Feminino , Hemangiossarcoma/tratamento farmacológico , Masculino , Projetos Piloto , Neoplasias Esplênicas/tratamento farmacológico , Sulfonamidas/administração & dosagem , Resultado do Tratamento
10.
Vet Rec Open ; 9(1): e49, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36329876

RESUMO

Background: Canine peripheral nodal T-cell lymphoma is considered chemotherapy resistant and carries a relatively poor prognosis. Prospective evaluations reporting the impact of chemotherapy on progression-free survival (PFS) and overall survival time for dogs with T-cell lymphoma are lacking. This study examined the impact of L-CHOP (L-asparaginase, doxorubicin, cyclophosphamide, vincristine, prednisone) chemotherapy or L-CHOP in combination with AT-005, a US Department of Agriculture-licensed caninised monoclonal antibody, on PFS and response rates in dogs with clinical intermediate- and high-grade peripheral nodal T-cell lymphoma. Methods: A prospective, randomised, placebo-controlled, investigator- and owner-blinded, multicentre study was completed. All dogs received a 19-week L-CHOP chemotherapy protocol with randomisation (1:1) into placebo or AT-005 groups. Response was evaluated via the Veterinary Cooperative Oncology Group criteria for canine lymphoma. Results: Forty-nine dogs were enrolled (25 received placebo and 24 received AT-005). Most demographic factors were similar between the two groups, with the exception that more dogs with stage IV and V disease were treated with AT-005 (34% vs. 8%; p = 0.03). Median PFS was 103 days (95% confidence interval [CI], 56-118) in the placebo group versus 64 days (95% CI, 36-118) in the AT-005 group. The overall response rate (ORR) for all dogs was 98% (48 of 49); complete response rate in the placebo group (64%) was not different from the AT-005 group (67%). Conclusions: To the best of the authors' knowledge, this is the first prospective study to document that treatment with L-CHOP chemotherapy, with or without AT-005, may result in a high ORR, but relatively brief PFS in dogs with clinical intermediate- and high-grade T-cell lymphoma.

11.
Vet Comp Oncol ; 20(4): 739-751, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35522017

RESUMO

One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for veterinary oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for the diagnosis of, and histopathologic prognostication for, canine cutaneous and oral/lip melanocytic neoplasms, suggest guidelines for reporting, provide recommendations for clinical interpretation, and discuss future directions. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists, American College of Veterinary Internal Medicine or the Veterinary Cancer Society.


Assuntos
Doenças do Cão , Neoplasias , Patologia Veterinária , Cães , Animais , Consenso , Doenças do Cão/diagnóstico , Oncologia , Neoplasias/veterinária
12.
Vet Comp Oncol ; 20(2): 458-464, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34878710

RESUMO

Primary pulmonary histiocytic sarcoma (PHS) is a rare form of dendritic cell or macrophage neoplasia originating within the pulmonary parenchyma. There is limited literature describing prognosis in dogs with PHS receiving curative-intent treatment consisting of surgical excision and adjuvant chemotherapy. The primary objective of this study was to report outcomes in dogs with localized PHS treated with standardized local and systemic therapy. A secondary objective was to identify prognostic factors in this population. A multi-institutional retrospective study was performed and medical records including all surgical and histopathologic reports were retrospectively reviewed. For inclusion, dogs were required to have confirmed localized PHS and they must have undergone curative-intent surgery with resection of all gross primary tumour and enlarged tracheobronchial lymph nodes; additionally, they must have received curative-intent treatment with adjuvant single-agent CCNU chemotherapy. Twenty-seven dogs from six veterinary teaching hospitals and five private practices treated from 2008-2019 were included. The overall median survival time was 432 days. Higher CCNU dose was demonstrated to have a negative impact on survival on univariate, but not multivariable, analysis. Factors that were not found to be associated with survival on univariate analysis included body weight, breed, clinical signs at the time of diagnosis, hypoalbuminaemia, tumour size, lung lobe affected, lymph node metastasis, surgical margins and CCNU dose reductions. This study supports a favourable prognosis for dogs diagnosed with localized PHS treated with curative-intent surgery in addition to adjuvant CCNU chemotherapy and suggests that multimodal treatment may be advisable to attempt to prolong survival.


Assuntos
Doenças do Cão , Sarcoma Histiocítico , Neoplasias Pulmonares , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/veterinária , Lomustina/uso terapêutico , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/veterinária , Estudos Retrospectivos , Resultado do Tratamento
13.
J Vet Intern Med ; 36(1): 215-226, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34952995

RESUMO

BACKGROUND: Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. HYPOTHESIS/OBJECTIVES: To determine the efficacy and safety of RAB in dogs with lymphoma. ANIMALS: One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. METHODS: Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. RESULTS: The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%). CONCLUSIONS AND CLINICAL IMPORTANCE: Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo.


Assuntos
Doenças do Cão , Linfoma , Alanina/análogos & derivados , Alanina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Doenças do Cão/tratamento farmacológico , Cães , Linfoma/tratamento farmacológico , Linfoma/veterinária , Purinas/uso terapêutico , Resultado do Tratamento
14.
Vet Comp Oncol ; 19(1): 92-98, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32729979

RESUMO

Canine osteosarcoma (OSA) is an aggressive bone tumour in dogs. Standard-of-care treatment typically results in relatively short survival times; thus, alternative treatments are needed to confer a survival advantage. It has been shown that OSA is an immunogenic tumour, suggesting that immune modulation may result in superior outcomes. A cryopreserved, Listeria-based OSA vaccine was recently developed and an initial study in dogs reported prolonged survival for patients receiving the vaccine in conjunction with standard-of-care. The goal of the current observational study was to report on the safety of the lyophilized formulation of this vaccine (the canine OSA vaccine, live Listeria vector [COV-LLV]) in a group of dogs previously diagnosed with OSA. Forty-nine (49) dogs received the COV-LLV and were included for analysis. Adverse events (AEs) noted during and after vaccinations were recorded. The AEs observed were typically mild and self-limiting, with nausea, lethargy and fever being most common. Four dogs (8%) cultured positive for Listeria (three infections including an amputation site abscess, septic stifle joint and bacterial cystitis; and one dog whose lungs cultured Listeria-positive on necropsy within 24 hours of COV-LLV administration). These cases join the previously reported Listeria-positive thoracic abscess that developed in a canine following use of COV-LLV. Although uncommon, it is important to realize this clinically significant AE is possible in patients treated with live therapeutic Listeria vaccines. As Listeria is zoonotic, caution is required not only for the patient receiving the vaccine, but also for the health care workers and family caring for the patient.


Assuntos
Neoplasias Ósseas/veterinária , Vacinas Anticâncer/imunologia , Doenças do Cão/prevenção & controle , Listeria/genética , Osteossarcoma/veterinária , Animais , Neoplasias Ósseas/prevenção & controle , Cães , Vetores Genéticos , Osteossarcoma/prevenção & controle
15.
Vet Comp Oncol ; 18(4): 763-769, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32346934

RESUMO

While current lymphoma therapies induce remission in most dogs, drug-resistant relapse is common, creating a need for novel agents. Rabacfosadine (RAB), a double prodrug of the acyclic nucleotide phosphonate 9-(2-phosphonylmethoxyethel) guanine (PMEG), preferentially targets lymphoma cells with reduced systemic toxicity compared with PMEG. Previous studies evaluating RAB administered every 21 days have suggested efficacy in both naïve and relapsed subjects; however, no large studies of RAB as a single agent have been reported in previously untreated dogs with intermediate to large cell lymphoma. The purpose of this study was to evaluate the safety and efficacy of RAB in dogs with previously untreated (excluding corticosteroids) lymphoma. Sixty-three dogs received up to five RAB treatments every 21 days (16 at 0.82 mg/kg and 47 at 1.0 mg/kg) as a 30 minutes intravenous infusion, with (n = 23) or without (n = 40) concurrent corticosteroids. Response assessment and adverse event (Ae) evaluation were performed every 21 days via Veterinary Cooperative Oncology Group (VCOG) criteria. The overall response rate was 87% (52% CR, 35% PR). The overall median progression free interval was 122 days (199 for CR, 89 for PR and 153 days for all responders). T-cell immunophenotype and corticosteroid pre-treatment were predictive of inferior outcomes on multivariate analysis. AEs were most commonly of gastrointestinal origin (hyporexia/diarrhoea) and generally resolved with supportive treatment and/or dosage adjustment. Three dogs experienced VCOG-CTCAE grade 5 delayed pulmonary fibrosis. In conclusion, RAB administered every 3 weeks is generally well tolerated and demonstrates substantial antitumour activity in dogs with previously untreated intermediate to large cell lymphoma.


Assuntos
Alanina/análogos & derivados , Doenças do Cão/tratamento farmacológico , Linfoma/veterinária , Purinas/farmacologia , Alanina/farmacologia , Animais , Cães , Feminino , Linfoma/tratamento farmacológico , Masculino , Resultado do Tratamento
16.
J Vet Intern Med ; 34(2): 882-889, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32064697

RESUMO

BACKGROUND: Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naïve and previously treated dogs. Its use in combination with L-asparaginase (L-ASP) has not been studied. HYPOTHESIS/OBJECTIVES: To evaluate the safety and efficacy of L-ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. ANIMALS: Fifty-two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin-based chemotherapy protocol. METHODS: Open-label, multicenter, prospective single-arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L-asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. RESULTS: The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression-free survival time (MPFS) was 63 days (range 5-428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44-428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L-ASP were negative prognostic factors on multivariate analysis. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent RAB/L-ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.


Assuntos
Alanina/análogos & derivados , Antineoplásicos/uso terapêutico , Asparaginase/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma/veterinária , Recidiva Local de Neoplasia/veterinária , Purinas/uso terapêutico , Alanina/administração & dosagem , Alanina/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Asparaginase/administração & dosagem , Colorado , Intervalo Livre de Doença , Cães , Feminino , Linfoma/tratamento farmacológico , Linfoma/mortalidade , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Prospectivos , Purinas/administração & dosagem , Indução de Remissão , Washington , Wisconsin
17.
Vet Clin North Am Small Anim Pract ; 49(5): 855-879, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31186126

RESUMO

Histiocytic sarcoma (HS) and hemangiosarcoma (HSA) are uncommon and aggressive neoplasms that develop much more frequently in dogs than in cats. Breed-specific predispositions have been identified for both cancers. The development of novel diagnostics is underway and may aid in earlier diagnosis. Therapeutic approaches to HS and HSA depend on the stage of disease and may include surgery, radiation therapy, and chemotherapy. Such interventions improve outcome; however, aside from a small number of clinical circumstances, both diseases are considered largely incurable. Continued efforts toward the identification of driver mutations and subsequent druggable targets may lead to improvements in long-term prognosis.


Assuntos
Doenças do Gato/patologia , Doenças do Gato/terapia , Doenças do Cão/patologia , Doenças do Cão/terapia , Hemangiossarcoma/veterinária , Sarcoma Histiocítico/veterinária , Animais , Doenças do Gato/epidemiologia , Gatos , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/veterinária , Doenças do Cão/epidemiologia , Cães , Hemangiossarcoma/epidemiologia , Hemangiossarcoma/patologia , Hemangiossarcoma/terapia , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/terapia , Cuidados Paliativos , Prognóstico , Radioterapia/métodos , Radioterapia/veterinária , Sobrevida
19.
Can J Vet Res ; 83(3): 187-196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308591

RESUMO

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.


Les avantages proposés de la chimiothérapie intra-artérielle (CIA) sont basés sur les prémisses d'une escalade de la dose locale à la tumeur et d'une disponibilité réduite des drogues systémiques. Il y a un manque de données pharmacocinétiques objectives pour confirmer l'avantage de l'administration de CIA chez les chiens avec des tumeurs urogénitales se produisant naturellement. L'objectif de la présente étude était de déterminer si l'administration de CIA lors de tumeurs urogénitales résulterait en une diminution de l'exposition systémique aux drogues lorsque comparé aux voies intraveineuses. Vingt-deux chiens avec des tumeurs urogénitales d'occurrence naturelle participèrent à cette étude cas-témoin prospective. De la mitoxantrone, de la doxorubicine, ou de la carboplatine furent administrées par CIA et voies intraveineuses [intraveineuse éveillée (chimiothérapie intraveineuse ­ CIV) et sous anesthésie générale (CIVAG)] à 3 sem d'intervalle. Des analyses du sérum furent utilisées afin de déterminer l'étendue de l'exposition systémique aux drogues. Le pic de la concentration sérique systémique normalisé pour la dose (Cmax) et la surface sous la courbe de la concentration sérique de la drogue-temps (SSC) furent utilisés pour quantifier l'exposition systémique. Un total de 26 traitements à la mitoxantrone fut administré à 10 chiens. Bien qu'il n'y ait pas de différence significative dans le Cmax, la SSC était significativement plus basse après la CIA comparativement à la CIVAG. Dix traitements de doxorubicine furent administrés à cinq chiens. Il n'y avait pas de différence significative dans le Cmax ou ls SSC. Un total de 14 traitements de carboplatine fut administré à sept chiens. Le Cmax était significativement plus bas pour la CIA comparativement à la CIV, alors que les valeurs de SSC étaient équivoques. Cette étude démontre que certaines valeurs sériques plus faibles peuvent être obtenues après CIA avec la carboplatine et la mitoxantrone. Ces agents de chimiothérapie pourraient avoir un profil pharmacologique préférentiel pour livraison régionale de chimiothérapie chez les chiens avec des tumeurs urogénitales.(Traduit par Docteur Serge Messier).


Assuntos
Carboplatina/uso terapêutico , Doenças do Cão/tratamento farmacológico , Injeções Intra-Arteriais/veterinária , Injeções Intravenosas/veterinária , Mitoxantrona/uso terapêutico , Neoplasias Urológicas/veterinária , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/sangue , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Área Sob a Curva , Carboplatina/administração & dosagem , Carboplatina/sangue , Carboplatina/farmacocinética , Cães , Feminino , Masculino , Mitoxantrona/administração & dosagem , Mitoxantrona/sangue , Mitoxantrona/farmacocinética , Projetos Piloto , Neoplasias Urológicas/tratamento farmacológico
20.
Vet Comp Oncol ; 17(4): 451-455, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31264352

RESUMO

One of the primary objectives of the Oncology-Pathology Working Group (OPWG), a joint initiative of the Veterinary Cancer Society and the American College of Veterinary Pathologists, is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for oncologic pathology. Consensus is established through critical review of peer-reviewed literature relevant to a subgroup's particular focus. Subsequent acceptance and approval of the document by the OPWG membership at large establishes consensus. The intent of this publication is to help educate practitioners and pathologists on the value of diagnostics related to the KIT receptor tyrosine kinase for canine cutaneous mast cell tumours and to provide a guide for the use of these tests in veterinary medicine. This document represents the opinions of the OPWG and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists or the Veterinary Cancer Society.


Assuntos
Doenças do Cão/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Mastocitoma/veterinária , Proteínas Proto-Oncogênicas c-kit/metabolismo , Neoplasias Cutâneas/veterinária , Animais , Cães , Mastocitoma/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Cutâneas/metabolismo
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