RESUMO
Quality of life (QOL) in dogs with cancer is a key consideration in the assessment of cancer treatment options. Despite interest in dietary strategies to improve management of oncology patients, there have been very few clinical studies showing the impact of diet on adverse effects of chemotherapy in dogs. This study was a randomised, controlled, double-blinded, multicenter clinical trial to investigate a high-protein, increased-fibre diet supplemented with omega-3 fatty acids, for dogs with cancer undergoing standard-of-care chemotherapy. Client-owned dogs with newly diagnosed grade 2 or higher mast cell tumours (or non-resectable/incompletely resected tumours) or multicentric lymphoma were randomised to receive the test diet (n = 24) or control diet (n = 21) for 8 weeks. Primary outcomes were QOL assessments, faecal scores, and blood concentrations of C-reactive protein and monocyte chemoattractant protein-1. Of 12 QOL parameters, 10 significantly improved from baseline to Week 8 in the test group compared with one in the control group. However, differences between the two groups were only statistically significant for 'frequency of signs of illness' (P = .009). There were no significant differences in the incidence of any adverse events, including gastrointestinal adverse events or clinically significant differences in laboratory parameters or faecal scores between the two groups. The absence of an observed negative impact of the test diet, combined with the magnitude of QOL improvements associated with the diet, suggest that a larger trial is warranted.
Assuntos
Ração Animal , Doenças do Cão , Ácidos Graxos Ômega-3 , Neoplasias , Animais , Cães , Doenças do Cão/tratamento farmacológico , Ácidos Graxos Ômega-3/administração & dosagem , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Qualidade de Vida , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversosRESUMO
OBJECTIVE: To evaluate survival times for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. ANIMALS: 109 client-owned dogs recruited from 15 institutions in the United States. PROCEDURES: Dogs were treated with prednisone at a dosage of 40 mg/m2, PO, once daily for 7 days and at a dosage of 20 mg/m2, PO, once daily thereafter. Quality of life (QOL) was assessed by owners with a visual analog scale when treatment was started (day 0), 1 and 2 weeks after treatment was started, and every 4 weeks thereafter. The primary outcome of interest was survival time as determined by the Kaplan-Meier method. Factors potentially associated with survival time were examined. RESULTS: Median overall survival time was 50 days (95% CI, 41 to 59 days). Factors associated with survival time included substage (a vs b) and immunophenotype (B cell vs T cell). Owner-assigned QOL scores on days 0 and 14 were significantly positively correlated with survival time. When QOL score was dichotomized, dogs with day 0 or day 14 QOL scores ≥ 50 had significantly longer survival times, compared with dogs with day 0 or day 14 QOL scores < 50. No variables were predictive of long-term (> 120 days) survival. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that survival times were short for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone. Owner-perceived QOL and clinician-assigned substage were both associated with survival time. Findings provide potentially important information for clinicians to discuss with owners of dogs with lymphoma at the time treatment decisions are made.
Assuntos
Doenças do Cão , Linfoma não Hodgkin , Linfoma , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doenças do Cão/tratamento farmacológico , Cães , Linfoma/tratamento farmacológico , Linfoma/veterinária , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/veterinária , Prednisona/uso terapêutico , Qualidade de VidaRESUMO
BACKGROUND: Prognosis associated with lymphoma in horses is poorly characterized, and treatment is often palliative. Long-term outcome after chemotherapy for horses with lymphoma is not well documented. OBJECTIVE: To report long-term outcome of horses with lymphoma treated with chemotherapy. ANIMALS: Fifteen equids. METHODS: Retrospective case series. Medical record search and call for cases on the ACVIM listserv for horses treated with chemotherapy for lymphoma. RESULTS: Fifteen cases with adequate data were identified. Complete remission was achieved in 5 horses (33.3%), partial response was achieved in 9 equids (60%), and stable disease was achieved in 1 horse. Overall response rate was 93.3% (14/15). Overall median survival time was 8 months (range, 1-46 months). Nine horses experienced a total of 14 adverse effects attributable to chemotherapy. Adverse effects were graded according to the Veterinary Cooperative Oncology Group common terminology criteria for adverse events grading system (grade 1 alopecia, n = 2; grade 1 neutropenia, n = 2; grade 1 lymphopenia, n = 3; grade 1 lethargy, n = 1; grade 2 neurotoxicity, n = 1; grade 2 colic, n = 1; grade 1 hypersensitivity, n = 1; grade 2 hypersensitivity, n = 2; grade 5 hypersensitivity, n = 1). Higher grade adverse effects most commonly were associated with doxorubicin administration (n = 4), including 1 horse that died 18 hours post-administration. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy can be used successfully for treatment of horses with lymphoma. Adverse effects, most commonly mild, occurred in approximately two-thirds of treated horses.
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças dos Cavalos/tratamento farmacológico , Linfoma/veterinária , Resultado do Tratamento , Animais , Equidae , Feminino , Cavalos , Linfoma/tratamento farmacológico , Masculino , Indução de Remissão , Estudos RetrospectivosRESUMO
Combination chemotherapy can be an effective option for treating resistant lymphoma in dogs. This retrospective study examined the tolerability and efficacy of the combination of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (dacarbazine) (DTIC) in a population of dogs with lymphoma resistant to a doxorubicin-containing chemotherapy protocol. Mitoxantrone was administered at 5 mg/m2 IV over 10 min followed by DTIC at 600 mg/m2 IV over 5 hr, every 3 wk. All dogs were treated with prophylactic trimethoprim-sulfadiazine and metoclopramide. The frequency of grade 4 neutropenia was 18%, and 5% of dogs were hospitalized from sepsis. Gastrointestinal toxicity was uncommon. The overall response rate was 34% (15 of 44; 95% confidence interval 20-48%) for a median duration of 97 days (range 24-636 days, 95% confidence interval 44-150 days). Fourteen of 15 dogs who received mitoxantrone and DTIC as first rescue responded to treatment. Dogs who achieved complete remission to their initial L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy protocol were more likely to respond to mitoxantrone and DTIC (23 versus 11%, P = .035). The combination of mitoxantrone and DTIC is a safe treatment option for resistant lymphoma in dogs.
Assuntos
Antineoplásicos/uso terapêutico , Dacarbazina/uso terapêutico , Linfoma/veterinária , Mitoxantrona/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doenças do Cão/tratamento farmacológico , Cães , Relação Dose-Resposta a Droga , Feminino , Linfoma/tratamento farmacológico , Masculino , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/veterinária , Estudos RetrospectivosRESUMO
OBJECTIVE To determine histologic and clinical factors associated with survival time in dogs with stage II splenic hemangiosarcoma treated by splenectomy and a chemotherapy protocol in which an anthracycline was alternated with lomustine. DESIGN Retrospective case series. ANIMALS 30 dogs with stage II splenic hemangiosarcoma. PROCEDURES Medical records of 3 facilities were reviewed to identify dogs treated for stage II splenic hemangiosarcoma between June 2011 and October 2014. Information collected included signalment, disease staging data, whether anemia was present, date of splenectomy, chemotherapy protocol, adverse effects, and date of death or last follow-up. Histologic slides were reviewed and scored by pathologists. Associations between variables of interest and survival data were evaluated statistically. RESULTS Median survival time for all dogs was 158 days (range, 55 to 560 days), and the 1-year survival rate was 16%. On multivariate analysis, only the histologically determined mitotic score was significantly associated with survival time. The median survival time of 292 days for dogs with a mitotic score of 0 (< 11 mitoses/10 hpf; n = 9) was significantly longer than that for dogs with higher scores (indicating higher mitotic rates); the 1-year survival rate for these dogs was 42%. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that future studies should take histologic factors, particularly mitotic rate, as well as tumor stage into account when assessing treatment effects on survival time of dogs with splenic hemangiosarcoma.
Assuntos
Quimioterapia Adjuvante , Doenças do Cão/mortalidade , Hemangiossarcoma/veterinária , Esplenectomia/veterinária , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Cães , Feminino , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/mortalidade , Hemangiossarcoma/cirurgia , Masculino , Estudos RetrospectivosRESUMO
This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg ± 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg ± 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Ciclofosfamida/uso terapêutico , Doenças do Cão/tratamento farmacológico , Lomustina/uso terapêutico , Linfoma/veterinária , Administração Oral , Animais , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doenças do Cão/patologia , Cães , Relação Dose-Resposta a Droga , Esquema de Medicação/veterinária , Lomustina/administração & dosagem , Lomustina/efeitos adversos , Linfoma/tratamento farmacológico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE-To determine outcome of dogs with presumed primary hepatic lymphoma treated with various multiagent, doxorubicin-based chemotherapeutic protocols and identify factors associated with prognosis. DESIGN-Retrospective case series. ANIMALS-18 dogs with presumed primary hepatic lymphoma. PROCEDURES-Medical records were reviewed for information on signalment, treatment, and outcome. RESULTS-8 dogs had a complete remission (CR), with a median remission duration of 120 days. Dogs with leukocytosis, neutrophilia, hypoalbuminemia, hyperbilirubinemia, or a combination of hypoalbuminemia and hyperbilirubinemia were less likely to achieve a CR. Overall median survival time (MST) was 63 days (range, 2 to 402 days). In a multivariate analysis, response to treatment and serum albumin concentration were associated with MST. Dogs that did not achieve a CR had a significantly shorter MST than did dogs that did achieve a CR (13 vs 283 days, respectively). Dogs with serum albumin concentration < 2.5 g/dL at the time treatment was initiated had a significantly shorter MST than did dogs with serum albumin concentration within reference limits (10 vs 128 days, respectively). There was also a positive correlation between serum albumin concentration and survival time (r = 0.74). CONCLUSIONS AND CLINICAL RELEVANCE-Results suggested that dogs with primary hepatic lymphoma that underwent chemotherapy had a poor prognosis, with a low response rate. Dogs that responded to treatment had a better prognosis, and dogs with hypoalbuminemia had a poorer prognosis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/terapia , Neoplasias Hepáticas/veterinária , Linfoma/veterinária , Animais , Cães , Feminino , Neoplasias Hepáticas/terapia , Linfoma/terapia , Masculino , Estudos RetrospectivosRESUMO
Epidemiological data indicate that low serum vitamin D concentrations are associated with an increased risk of a variety of human tumours. Cutaneous mast cell tumours (MCT) occur more frequently in dogs than in any other species. Canine MCT express the vitamin D receptor, and vitamin D derivatives have in vitro and in vivo anti-tumour activity. We sought to examine the association between vitamin D serum level and MCT in Labrador retrievers, a dog breed predisposed to MCT development. To examine this association, serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations were examined in eighty-seven Labrador retrievers, including thirty-three with MCT and fifty-four unaffected controls. The relationship between cases and controls and 25(OH)D3 level, age and body condition score were evaluated using univariate and multivariate analyses. Potential differences in vitamin D oral intake, calculated on the basis of a dietary questionnaire, were also evaluated between groups. Mean 25(OH)D3 concentration (104 (SD 30) nmol/l) in dogs with MCT was significantly lower than that of unaffected dogs (120 (SD 35) nmol/l; P = 0.027). The mean calculated vitamin D intake per kg body weight in Labrador retrievers with MCT was not statistically different from that of unaffected Labrador retrievers (0.38 (SD 0.25) and 0.31 (SD 0.22) µg/kg body weight, respectively; P = 0.13). These findings suggest that low levels of 25(OH)D3 might be a risk factor for MCT in Labrador retrievers. Prospective cohort studies are warranted.
Assuntos
Calcifediol/sangue , Doenças do Cão/etiologia , Mastocitoma/veterinária , Neoplasias Cutâneas/veterinária , Deficiência de Vitamina D/veterinária , Animais , Estudos Transversais , Cães , Feminino , Masculino , Mastocitoma/classificação , Mastocitoma/etiologia , Fatores de Risco , Neoplasias Cutâneas/etiologia , Deficiência de Vitamina D/complicaçõesRESUMO
OBJECTIVE: To evaluate factors associated with second remission in dogs with lymphoma retreated with a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) protocol after relapse following initial treatment with a first-line 6-month CHOP protocol. DESIGN: Retrospective case series. ANIMALS: 95 dogs with lymphoma. PROCEDURES: Medical records were reviewed. Remission duration was estimated by use of the Kaplan-Meier method. Factors potentially associated with prognosis were examined. RESULTS: Median remission duration after the first-line CHOP protocol was 289 days (range, 150 to 1,457 days). Overall, 78% (95% confidence interval [CI], 69% to 86%) of dogs achieved a complete remission following retreatment, with a median second remission duration of 159 days (95% CI, 126 to 212 days). Duration of time off chemotherapy was associated with likelihood of response to retreatment; median time off chemotherapy was 140 days for dogs that achieved a complete remission after retreatment and 84 days for dogs that failed to respond to retreatment. Second remission duration was associated with remission duration after initial chemotherapy; median second remission duration for dogs with initial remission duration ≥ 289 days was 214 days (95% CI, 168 to 491 days), compared with 98 days (95% CI, 70 to 144 days) for dogs with initial remission duration < 289 days. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that retreatment with the CHOP protocol can be effective in dogs with lymphoma that successfully complete an initial 6-month CHOP protocol.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Linfoma/veterinária , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Cães , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Esquema de Medicação , Linfoma/tratamento farmacológico , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Vincristina/administração & dosagem , Vincristina/uso terapêuticoRESUMO
PURPOSE: High-dose calcitriol (1,25-dihydroxyvitamin D(3)) has antineoplastic activity against a range of tumors and potentiates chemotherapeutic agents. In an earlier canine study, the MTD of intravenous (i.v.) calcitriol was 3.75 µg/kg, but polysorbate-associated hypersensitivity reactions were common. Use of commercially available oral calcitriol is limited by the absence of a formulation of suitable strength to allow administration of a reasonable number of caplets. This study evaluated the bioavailability of DN101, a concentrated oral calcitriol formulation specifically developed for anticancer applications. METHODS: An open-label, single-dose, 2-way crossover study was conducted. Dogs randomly received a single 3.75 µg/kg dose of calcitriol either i.v. or oral (as DN101), followed by cisplatin (60 mg/m(2)). Three weeks later, the alternate form of calcitriol was given prior to another dose of cisplatin. Dogs received antihistamines and corticosteroids prior to both treatments. Food was withheld for 12 h before and after therapy. Serum calcitriol concentrations were measured by radioimmunoassay. RESULTS: Ten tumor-bearing dogs received both i.v. and oral calcitriol. Six dogs experienced hypersensitivity reactions during i.v. calcitriol. Sequence of calcitriol administration (day-1 vs. day-21) by either i.v. or oral routes had no effect on the major calcitriol pharmacokinetic parameters. Oral calcitriol resulted in significantly lower values for AUC (P = 0.05) and prolonged T (1/2) (P = 0.003) when compared to i.v. Calcitriol oral bioavailability was highly variable among dogs (mean ± SEM, 71 ± 12.6%). CONCLUSIONS: This study demonstrates that a high-dose formulation of calcitriol has a moderate bioavailability in dogs, but inter-individual variability in PK parameters is similar to that observed in people. With this bioavailability, serum concentrations of calcitriol that exhibit antitumor activity in a preclinical murine model were achieved in some dogs. Exploration of methods to minimize variation in calcitriol systemic exposure is warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Calcitriol/farmacocinética , Hipersensibilidade a Drogas/etiologia , Neoplasias/tratamento farmacológico , Administração Oral , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Área Sob a Curva , Disponibilidade Biológica , Calcitriol/administração & dosagem , Cisplatino/administração & dosagem , Estudos Cross-Over , Doenças do Cão , Cães , Esquema de Medicação , Meia-Vida , Infusões Intravenosas , Dose Máxima Tolerável , Neoplasias/veterinária , Radioimunoensaio , Distribuição AleatóriaRESUMO
OBJECTIVE: To determine whether a glomerular filtration rate (GFR) assay based on serum iohexol clearance can be used to predict carboplatin clearance in cats. ANIMALS: 10 cats with tumors. PROCEDURES: GFR was measured concurrently by use of plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) to yield GFR(99mTc-DTPA) and serum clearance of iohexol to yield GFR(Iohexol). A single dose of carboplatin was administered IV as a bolus. Dose was calculated by use of a target value for the area under the plasma platinum concentration-versus-time curve (AUC(Target)) and estimation of platinum clearance (CL(PT)) derived from GFR(99mTc-DTPA) as follows: dose = AUC(Target) x 2.6 x GFR(99mTc-DTPA) x body weight, where AUC(Target) is 2.75 min.mg.mL(-1). Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR(99mTc-DTPA) and GFR(Iohexol) were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CL(PT) could be predicted from GFR(99mTc-DTPA) or GFR(Iohexol) (or both). RESULTS: GFR(99mTc-DTPA) and GFR(Iohexol) were strongly correlated (r = 0.90), but GFR(Iohexol) values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR(99mTc-DTPA) (CL(PT) = 2.5 x GFR(99mTc-DTPA)) and to GFR(Iohexol) (CL(PT) = [1.3 x GFR(Iohexol)] + 1.4). CONCLUSIONS AND CLINICAL RELEVANCE: In cats, serum iohexol clearance was an accurate predictor of CL(PT) and can be used to calculate the carboplatin dose as follows: dose = AUC(Target) x ([1.3 x GFR(Iohexol)] + 1.4) x body weight.
Assuntos
Carboplatina/metabolismo , Gatos/metabolismo , Taxa de Filtração Glomerular/fisiologia , Iohexol/metabolismo , Animais , Área Sob a Curva , Superfície Corporal , Peso Corporal , Carboplatina/sangue , Carcinoma/tratamento farmacológico , Carcinoma/fisiopatologia , Carcinoma/veterinária , Doenças do Gato/tratamento farmacológico , Doenças do Gato/fisiopatologia , Cromatografia Líquida de Alta Pressão , Taxa de Depuração Metabólica , Sarcoma/tratamento farmacológico , Sarcoma/fisiopatologia , Sarcoma/veterinária , Pentetato de Tecnécio Tc 99m/farmacocinéticaRESUMO
OBJECTIVE: To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUC(Target)) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUC(Target). ANIMALS: 32 cats with tumors. PROCEDURES: In each cat, plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid was measured to assess GFR. Carboplatin was administered IV. The dose was calculated by use of an equation as follows: Dose = AUC(Target) x 2.6 x GFR x body weight. Initial AUC(Target) was 2.0 min.mg.mL(-1) and was increased in increments of 0.50 min.mg.mL(-1) in cohorts of 3 cats. To assess myelotoxic effects, CBCs were performed weekly for > or = 4 weeks. Following identification of the maximum tolerated AUC(Target), additional cats were treated at that AUC(Target) and plasma platinum concentrations were measured in 6 cats. RESULTS: The AUC(Target) values ranged from 2.0 to 3.0 min.mg.mL(-1). Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUC(Target) was 2.75 min.mg.mL(-1). Nineteen cats received this dose of carboplatin; 13 became neutropenic, but only 1 developed severe neutropenia (< 500 neutrophils/microL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUC(Target) and the measured value ranged from -0.23 to 0.31 min.mg.mL(-1) (median, 0.20 min.mg.mL(-1)). CONCLUSIONS AND CLINICAL RELEVANCE: In cats, carboplatin-associated myelotoxicoses were accurately and uniformly predicted by use of the proposed dosing strategy. The maximum tolerated AUC(Target) for a single dose of carboplatin was 2.75 min.mg.mL(-1).
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Doenças do Gato/tratamento farmacológico , Neoplasias/veterinária , Polivinil/administração & dosagem , Polivinil/uso terapêutico , Resinas Acrílicas , Animais , Antineoplásicos/efeitos adversos , Área Sob a Curva , Gatos , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular , Masculino , Neoplasias/tratamento farmacológico , Polivinil/efeitos adversosRESUMO
OBJECTIVE: To characterize oral bioavailability and pharmacokinetic disposition of etoposide when the IV formulation was administered orally to dogs. ANIMALS: 8 tumor-bearing dogs. PROCEDURES: An open-label, single-dose, 2-way crossover study was conducted. Dogs were randomly assigned to initially receive a single dose of etoposide (50 mg/m2) IV or PO. A second dose was administered via the alternate route 3 to 7 days later. Medications were administered before IV administration of etoposide to prevent hypersensitivity reactions. Oral administration of etoposide was prepared by reconstituting the parenteral formulation with 0.9% NaCl solution and further diluting the reconstituted mixture 1:1 with a sweetening agent. Plasma samples were obtained after both treatments. Etoposide concentrations were measured with a high-performance liquid chromatography assay, and plasma etoposide concentration-time profiles were analyzed by use of noncompartmental methods. RESULTS: 4 dogs had hypersensitivity reactions during IV administration of etoposide. No adverse effects were detected after oral administration. Plasma etoposide concentrations were undetectable in 2 dogs after oral administration. Oral administration of etoposide resulted in significantly lower values for the maximum plasma concentration and the area under the plasma etoposide concentration-versus-time curve, compared with results for IV administration. Oral bioavailability of etoposide was low (median, 13.4%) and highly variable among dogs (range, 5.7% to 57.3%). CONCLUSIONS AND CLINICAL RELEVANCE-Vehicle-related toxicosis can limit the IV administration of etoposide in dogs. The parenteral formulation of etoposide can be safely administered orally to dogs, but routine use was not supported because of low and variable oral bioavailability in this study.
Assuntos
Doenças do Cão/tratamento farmacológico , Etoposídeo/farmacocinética , Neoplasias/veterinária , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Estudos Cross-Over , Cães , Etoposídeo/administração & dosagem , Etoposídeo/sangue , Etoposídeo/uso terapêutico , Infusões Intravenosas , Cinética , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVE: To determine clinical activity and toxic effects of lomustine when used to treat cats with mast cell tumors (MCTs). DESIGN: Retrospective case series. ANIMALS: 38 cats with measurable, histologically or cytologically confirmed MCTs treated with lomustine at a dosage > or = 50 mg/m(2). PROCEDURES: Medical records were reviewed to determine response to treatment and evidence of drug toxicoses. The Kaplan-Meier method was used to estimate remission duration. RESULTS: 26 cats had cutaneous MCTs, 7 had MCTs of the mesenteric lymph nodes, 2 had gastrointestinal tract MCTs, 2 had hepatic MCTs, and 1 had MCTs involving multiple organs. Targeted lomustine dosage was 50 mg/m(2) in 22 cats and 60 mg/m(2) in 16 cats. Median administered dosage of lomustine was 56 mg/m(2) (range, 48 to 65 mg/m(2)), and median number of doses administered was 2 (range, 1 to 12). Seven cats had a complete response and 12 had a partial response, for an overall response rate of 50%. Median response duration was 168 days (range, 25 to 727 days). The most common toxicoses were neutropenia and thrombocytopenia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that lomustine had activity against MCTs in cats and was well tolerated. Further, findings suggested that treatment with lomustine should be considered for cats with MCTs for which local treatment is not an option.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Doenças do Gato/tratamento farmacológico , Lomustina/uso terapêutico , Linfoma/veterinária , Sarcoma de Mastócitos/veterinária , Neoplasias Cutâneas/veterinária , Animais , Antineoplásicos Alquilantes/efeitos adversos , Doenças do Gato/patologia , Gatos , Feminino , Estimativa de Kaplan-Meier , Lomustina/efeitos adversos , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Sarcoma de Mastócitos/tratamento farmacológico , Sarcoma de Mastócitos/patologia , Recidiva Local de Neoplasia/veterinária , Estadiamento de Neoplasias/veterinária , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate factors associated with response to treatment, remission duration, and survival in cats with low-grade lymphoma affecting various organ systems. DESIGN: Retrospective case series. SAMPLE POPULATION: 41 cats with histologically confirmed low-grade lymphocytic lymphoma. PROCEDURES: Medical records and biopsy specimens of cats with histologically confirmed low-grade lymphocytic lymphoma of various organ systems treated with prednisone and chlorambucil between 1995 and 2005 were reviewed. The Kaplan-Meier method was used to estimate remission duration and survival. Factors potentially associated with prognosis were compared. RESULTS: Common clinical signs were weight loss (83%), vomiting (73%), anorexia (66%), and diarrhea (58%). Seventy-eight percent of cats tested had low serum cobalamin concentrations. Lymphoma was confined to the gastrointestinal tract in 68% of cats. Fifty-six percent of cats achieved a complete response to treatment, and 39% achieved a partial response. Five percent of cats had no response. No association was found between any risk factors (including anatomic site) and response to treatment. Partial response was associated with shorter remission duration, compared with complete response; median remission duration was 428 days for cats achieving a partial response, compared with 897 days for cats achieving a complete response. No other factors were associated with remission duration. Overall median survival time was 704 days. No factors were significantly associated with survival time. CONCLUSIONS AND CLINICAL RELEVANCE: Most cats with lymphocytic lymphoma responded to treatment with prednisone and chlorambucil, and most factors evaluated were not associated with outcome.
Assuntos
Doenças do Gato/tratamento farmacológico , Clorambucila/uso terapêutico , Leucemia Linfocítica Crônica de Células B/veterinária , Prednisona/uso terapêutico , Indução de Remissão , Animais , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Doenças do Gato/mortalidade , Doenças do Gato/patologia , Gatos , Feminino , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Calcitriol potentiates cisplatin-mediated activity in a variety of tumor models. We examine here, the effect of calcitriol and cisplatin pre-clinically and clinically in canine spontaneous tumors through in vitro studies on tumor cells and through a phase I study of calcitriol and cisplatin to identify the maximum-tolerated dosage (MTD) of this combination in dogs with cancer and to characterize the pharmacokinetic disposition of calcitriol in dogs. METHODS: Canine tumor cells were investigated for calcitriol/cisplatin interactions on proliferation using an MTT assay in a median-dose effect analysis; data were used to derive a combination index (CI). Cisplatin was given at a fixed dosage of 60 mg/m2. Calcitriol was given i.v. and the dosage was escalated in cohorts of three dogs until the MTD was defined. Serum calcitriol concentrations were quantified by radioimmunoassay. RESULTS: In vitro, CIs < 1.0 were obtained for all combinations of calcitriol/cisplatin examined. The MTD was 3.75 microg/kg calcitriol in combination with cisplatin, and hypercalcemia was the dose-limiting toxicosis. The relationship between calcitriol dosage and either Cmax or AUC was linear. Calcitriol dosages >1.5 microg/kg achieved Cmax > or = 9.8 ng/mL and dosages >1.0 microg/kg achieved AUC > or = 45 h ng/mL. CONCLUSIONS: Calcitriol and cisplatin have synergistic antiproliferative effects on multiple canine tumor cells and high-dosages of i.v. calcitriol in combination with cisplatin can be safely administered to dogs. Cmax and AUC at the MTD 3.75 microg/kg calcitriol exceed concentrations associated with antitumor activity in a murine model, indicating this combination might have significant clinical utility in dogs.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Área Sob a Curva , Calcitriol/administração & dosagem , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Hipersensibilidade a Drogas/epidemiologia , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Doenças Hematológicas/induzido quimicamente , Doenças Hematológicas/epidemiologia , Injeções Intravenosas , Sais de Tetrazólio , Tiazóis , Vitaminas/administração & dosagemRESUMO
OBJECTIVE: To evaluate long-term function of vascular access ports (VAPs) implanted in the femoral vein of dogs and cats undergoing cancer treatment. DESIGN: Prospective clinical study. ANIMALS: 3 dogs and 6 cats treated via chemotherapy or radiation. PROCEDURES: VAPs were surgically implanted in the left femoral vein of 3 dogs and 6 cats over a 1-year period. Injection port location was alternated to either a caudal thoracic or ilial location in each patient. Duration of VAP function, ease of infusion, and ease of aspiration through the VAPs were recorded, and associated complications were assessed at each VAP use. Client satisfaction with VAP placement was evaluated by use of a questionnaire. RESULTS: Primary uses of the VAPs included blood sampling and delivering sedative or chemotherapeutic drugs. Median duration of successful infusion was 147 days (range, 60 to 370 days), and median duration of successful aspiration was 117 days (range, 10 to 271 days). The frequency of signs of VAP-related discomfort was low (7% of patient observations). Clients were satisfied with their decision to use VAPs. Complications included partial (n = 7) or complete (2) VAP occlusion, port migration (1), and presumptive infection (1). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that VAP implantation into the femoral vein provides an acceptable means of chronic venous access in dogs and cats undergoing cancer treatment.
Assuntos
Antineoplásicos/administração & dosagem , Cateteres de Demora/veterinária , Veia Femoral , Medicina Veterinária/instrumentação , Medicina Veterinária/métodos , Animais , Doenças do Gato/tratamento farmacológico , Cateteres de Demora/efeitos adversos , Cateteres de Demora/normas , Gatos , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Various diagnostic tests have been used to assign a clinical stage to dogs with lymphoma. As more sensitive staging methods are introduced, dogs are reclassified as having a higher disease stage, thereby affecting comparisons of dogs across differently staged clinical trials, and possibly, prognosis. HYPOTHESIS: The addition of more sensitive staging tests causes stage migration in dogs with lymphoma. ANIMALS: Fifty-nine client-owned dogs with previously untreated cytologically or histologically confirmed lymphoma METHODS: For every dog, the World Health Organization stage classification (I-V) was based on 5 groupings of various diagnostic tests: A (physical examination [PE] and quantitative blood count [QBC]), B (PE, QBC, thoracic and abdominal radiographs), C (PE, complete blood count with blood-smear evaluation [CBC], thoracic and abdominal radiographs), D (PE, CBC, thoracic radiographs, abdominal ultrasound), and E (PE, CBC, thoracic radiographs, abdominal ultrasound, and bone-marrow cytology). Dogs were treated with doxorubicin-based protocols. RESULTS: There was migration between all of the staging methods except D to E. However, the stage was not a predictor of remission rate, remission duration, or survival, regardless of staging method used. CONCLUSIONS AND CLINICAL IMPORTANCE: These data emphasized the need for standardized methods to determine the clinical stage in dogs with lymphoma.
Assuntos
Doenças do Cão/patologia , Linfoma/veterinária , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Células Sanguíneas/veterinária , Células da Medula Óssea/patologia , Doenças do Cão/tratamento farmacológico , Cães , Doxorrubicina/administração & dosagem , Feminino , Linfoma/tratamento farmacológico , Linfoma/patologia , Masculino , Estadiamento de Neoplasias/métodos , Estadiamento de Neoplasias/veterinária , Estudos Prospectivos , Radiografia Abdominal/veterinária , Radiografia Torácica/veterinária , Resultado do Tratamento , Ultrassonografia/veterináriaRESUMO
Squamous-cell carcinoma (SCC) is the second most common tumor in horses, and 40%-50% may occur in ocular and adnexal structures. Cyclooxygenase (COX)-2 is an inducible enzyme responsible for the production of prostaglandins that control cell growth and the development and progression of cancer. Mechanisms responsible for the initial upregulation of COX-2 in neoplasia are unclear; prolonged sunlight exposure and mutations in the p53 gene may be possibilities. Because the etiopathogenesis of ocular SCC in horses may involve ultraviolet sunlight and p53 mutations, the purpose of this study was to characterize the immunoreactivity of COX-2 in these tumors. Cyclooxygenase-2 expression was found in 6 of 22 (27%) paraffin-embedded equine SCCs. Cyclooxygenase-2 immunoreactivity was associated with the mitotic index (P < 0.001). Strategies to inhibit COX-2 by the use of topical or systemic COX-2 inhibitors might prove to be a safe and economical treatment in some horses with SCC.
Assuntos
Carcinoma de Células Escamosas/veterinária , Ciclo-Oxigenase 2/análise , Neoplasias Oculares/veterinária , Doenças dos Cavalos/enzimologia , Animais , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/imunologia , Ciclo-Oxigenase 2/imunologia , Neoplasias Oculares/enzimologia , Neoplasias Oculares/imunologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Doenças dos Cavalos/imunologia , CavalosRESUMO
CASE DESCRIPTION: 3 dogs (9 to 12 years old) were evaluated because of recurrent pleural effusion that was refractory to treatment of the underlying cause. CLINICAL FINDINGS: Dogs were evaluated because of cough, dyspnea, tachypnea, or lethargy or a combination of these clinical signs. Radiography, ultrasonography, or thoracocentesis were used to confirm the presence of pleural fluid in each dog. A neoplastic cause of pleural effusion was confirmed in 2 dogs. In 1 dog, fasciitis of the mediastinum and the left parietal pleura was diagnosed, with no evidence of neoplasia. TREATMENT AND OUTCOME: Each dog was anesthestized, and thoracotomy was performed with manual perforation of the mediastinum. Permanent, subcutaneously placed vascular access ports were attached to intrathoracic, Jackson-Pratt drain tubing for repeated drainage of pleural fluid. Drains were used successfully in the 3 dogs for periods of 6 weeks, 11 weeks, and > 3 years. CLINICAL RELEVANCE: Findings suggest that subcutaneous vascular access ports attached to intrathoracic drain tubing may be an effective way to remove recurrent pleural effusion in dogs.