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1.
Vet Comp Oncol ; 22(1): 2-11, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37933436

ABSTRACT

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.


Subject(s)
Animal Feed , Dog Diseases , Fatty Acids, Omega-3 , Neoplasms , Animals , Dogs , Dog Diseases/drug therapy , Fatty Acids, Omega-3/administration & dosage , Neoplasms/drug therapy , Neoplasms/veterinary , Quality of Life , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects
2.
J Am Vet Med Assoc ; 259(1): 62-71, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34125606

ABSTRACT

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.


Subject(s)
Dog Diseases , Lymphoma, Non-Hodgkin , Lymphoma , Animals , Antineoplastic Combined Chemotherapy Protocols , Cyclophosphamide/therapeutic use , Dog Diseases/drug therapy , Dogs , Lymphoma/drug therapy , Lymphoma/veterinary , Lymphoma, Non-Hodgkin/drug therapy , Lymphoma, Non-Hodgkin/veterinary , Prednisone/therapeutic use , Quality of Life
3.
J Vet Intern Med ; 33(2): 953-960, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30636061

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Horse Diseases/drug therapy , Lymphoma/veterinary , Treatment Outcome , Animals , Equidae , Female , Horses , Lymphoma/drug therapy , Male , Remission Induction , Retrospective Studies
4.
J Am Anim Hosp Assoc ; 55(2): 101-109, 2019.
Article in English | MEDLINE | ID: mdl-30653362

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Dacarbazine/therapeutic use , Lymphoma/veterinary , Mitoxantrone/therapeutic use , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Dog Diseases/drug therapy , Dogs , Dose-Response Relationship, Drug , Female , Lymphoma/drug therapy , Male , Mitoxantrone/administration & dosage , Mitoxantrone/adverse effects , Neutropenia/chemically induced , Neutropenia/veterinary , Retrospective Studies
5.
J Am Vet Med Assoc ; 251(5): 559-565, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28828962

ABSTRACT

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.


Subject(s)
Chemotherapy, Adjuvant , Dog Diseases/mortality , Hemangiosarcoma/veterinary , Splenectomy/veterinary , Animals , Dog Diseases/drug therapy , Dog Diseases/surgery , Dogs , Female , Hemangiosarcoma/drug therapy , Hemangiosarcoma/mortality , Hemangiosarcoma/surgery , Male , Retrospective Studies
6.
J Am Anim Hosp Assoc ; 50(3): 167-73, 2014.
Article in English | MEDLINE | ID: mdl-24659727

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Cyclophosphamide/therapeutic use , Dog Diseases/drug therapy , Lomustine/therapeutic use , Lymphoma/veterinary , Administration, Oral , Animals , Antineoplastic Agents, Alkylating/administration & dosage , Antineoplastic Agents, Alkylating/adverse effects , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Dog Diseases/pathology , Dogs , Dose-Response Relationship, Drug , Drug Administration Schedule/veterinary , Lomustine/administration & dosage , Lomustine/adverse effects , Lymphoma/drug therapy , Retrospective Studies , Treatment Outcome
7.
J Am Vet Med Assoc ; 239(7): 966-71, 2011 Oct 01.
Article in English | MEDLINE | ID: mdl-21961637

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dog Diseases/therapy , Liver Neoplasms/veterinary , Lymphoma/veterinary , Animals , Dogs , Female , Liver Neoplasms/therapy , Lymphoma/therapy , Male , Retrospective Studies
8.
Br J Nutr ; 106 Suppl 1: S60-3, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22005438

ABSTRACT

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.


Subject(s)
Calcifediol/blood , Dog Diseases/etiology , Mastocytoma/veterinary , Skin Neoplasms/veterinary , Vitamin D Deficiency/veterinary , Animals , Cross-Sectional Studies , Dogs , Female , Male , Mastocytoma/classification , Mastocytoma/etiology , Risk Factors , Skin Neoplasms/etiology , Vitamin D Deficiency/complications
9.
J Am Vet Med Assoc ; 238(4): 501-6, 2011 Feb 15.
Article in English | MEDLINE | ID: mdl-21320021

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dog Diseases/drug therapy , Lymphoma/veterinary , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cyclophosphamide/administration & dosage , Cyclophosphamide/therapeutic use , Dogs , Doxorubicin/administration & dosage , Doxorubicin/therapeutic use , Drug Administration Schedule , Lymphoma/drug therapy , Prednisone/administration & dosage , Prednisone/therapeutic use , Remission Induction , Retrospective Studies , Vincristine/administration & dosage , Vincristine/therapeutic use
10.
Cancer Chemother Pharmacol ; 67(1): 165-71, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20306264

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Calcitriol/pharmacokinetics , Drug Hypersensitivity/etiology , Neoplasms/drug therapy , Administration, Oral , Animals , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Area Under Curve , Biological Availability , Calcitriol/administration & dosage , Cisplatin/administration & dosage , Cross-Over Studies , Dog Diseases , Dogs , Drug Administration Schedule , Half-Life , Infusions, Intravenous , Maximum Tolerated Dose , Neoplasms/veterinary , Radioimmunoassay , Random Allocation
11.
Leuk Lymphoma ; 52(2): 273-84, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21133722

ABSTRACT

A pilot study of anti-human leukocyte antigen (HLA)-DR monoclonal antibody (mAb) in dogs with lymphoma was undertaken to verify the suitability of a canine model to address therapeutically relevant endpoints prior to a full trial in dogs, and ultimately human investigation. In vitro studies demonstrated that L243, a murine IgG1 anti-HLA-DR, binds to normal and malignant canine lymphocytes and induces apoptosis in canine lymphoma cells. Moreover, L243 was administered safely to normal dogs and dogs with lymphoma, and bound to malignant cells in nodal tissue. Preliminary evidence of transient disease stabilization was observed in a subset of dogs with advanced-stage lymphoma following L243 immunotherapy. hL243γ4P (IMMU-114), a humanized IgG4 anti-HLA-DR, currently under evaluation preclinically for human trials, was also shown to bind malignant canine lymphocytes, and safety and pharmacokinetic data from the administration of IMMU-114 to normal dogs indicate similar behavior to L243 in these assessments. These findings provide a rationale for the use of dogs with lymphoma in safety and efficacy evaluations of anti-HLA-DR mAbs for both veterinary and human applications.


Subject(s)
Antibodies, Anti-Idiotypic/pharmacology , Antibodies, Monoclonal/therapeutic use , HLA-DR Antigens/immunology , Immunotherapy , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/therapy , Animals , Antibodies, Anti-Idiotypic/immunology , Antibodies, Monoclonal/immunology , Antibody-Dependent Cell Cytotoxicity , Dogs , Female , Humans , Immunoglobulin G/immunology , Lymphoma, B-Cell/pathology , Pilot Projects
12.
Am J Vet Res ; 70(9): 1135-40, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19719430

ABSTRACT

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.


Subject(s)
Carboplatin/metabolism , Cats/metabolism , Glomerular Filtration Rate/physiology , Iohexol/metabolism , Animals , Area Under Curve , Body Surface Area , Body Weight , Carboplatin/blood , Carcinoma/drug therapy , Carcinoma/physiopathology , Carcinoma/veterinary , Cat Diseases/drug therapy , Cat Diseases/physiopathology , Chromatography, High Pressure Liquid , Metabolic Clearance Rate , Sarcoma/drug therapy , Sarcoma/physiopathology , Sarcoma/veterinary , Technetium Tc 99m Pentetate/pharmacokinetics
13.
Am J Vet Res ; 70(6): 770-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19496668

ABSTRACT

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).


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Cat Diseases/drug therapy , Neoplasms/veterinary , Polyvinyls/administration & dosage , Polyvinyls/therapeutic use , Acrylic Resins , Animals , Antineoplastic Agents/adverse effects , Area Under Curve , Cats , Dose-Response Relationship, Drug , Female , Glomerular Filtration Rate , Male , Neoplasms/drug therapy , Polyvinyls/adverse effects
14.
Am J Vet Res ; 69(10): 1316-22, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18828689

ABSTRACT

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.


Subject(s)
Dog Diseases/drug therapy , Etoposide/pharmacokinetics , Neoplasms/veterinary , Administration, Oral , Animals , Area Under Curve , Biological Availability , Cross-Over Studies , Dogs , Etoposide/administration & dosage , Etoposide/blood , Etoposide/therapeutic use , Infusions, Intravenous , Kinetics , Neoplasms/drug therapy
15.
J Am Anim Hosp Assoc ; 44(3): 116-23, 2008.
Article in English | MEDLINE | ID: mdl-18451069

ABSTRACT

Data from 48 dogs with nasal carcinomas treated with palliative radiation therapy (PRT) were retrospectively reviewed. Factors potentially influencing resolution of clinical signs and survival after PRT were evaluated. Clinical signs completely resolved in 66% of dogs for a median of 120 days. The overall median survival time was 146 days. Duration of response to PRT was shorter in dogs that had clinical signs for <90 days before PRT. Survival times were shorter in dogs that had partial or no resolution of clinical signs after PRT than in dogs that had complete resolution of clinical signs.


Subject(s)
Dog Diseases/radiotherapy , Nose Neoplasms/veterinary , Animals , Dog Diseases/mortality , Dogs , Dose Fractionation, Radiation , Female , Male , Nose Neoplasms/mortality , Nose Neoplasms/radiotherapy , Palliative Care , Records/veterinary , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
16.
J Am Vet Med Assoc ; 232(8): 1200-5, 2008 Apr 15.
Article in English | MEDLINE | ID: mdl-18412534

ABSTRACT

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.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Cat Diseases/drug therapy , Lomustine/therapeutic use , Lymphoma/veterinary , Mast-Cell Sarcoma/veterinary , Skin Neoplasms/veterinary , Animals , Antineoplastic Agents, Alkylating/adverse effects , Cat Diseases/pathology , Cats , Female , Kaplan-Meier Estimate , Lomustine/adverse effects , Lymphoma/drug therapy , Lymphoma/pathology , Male , Mast-Cell Sarcoma/drug therapy , Mast-Cell Sarcoma/pathology , Neoplasm Recurrence, Local/veterinary , Neoplasm Staging/veterinary , Prognosis , Retrospective Studies , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Treatment Outcome
17.
Cancer Chemother Pharmacol ; 62(5): 881-91, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18246349

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dog Diseases/drug therapy , Neoplasms/drug therapy , Neoplasms/veterinary , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Area Under Curve , Calcitriol/administration & dosage , Cell Line, Tumor , Cisplatin/administration & dosage , Dogs , Dose-Response Relationship, Drug , Drug Hypersensitivity/epidemiology , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Hematologic Diseases/chemically induced , Hematologic Diseases/epidemiology , Injections, Intravenous , Tetrazolium Salts , Thiazoles , Vitamins/administration & dosage
18.
J Am Vet Med Assoc ; 232(3): 405-10, 2008 Feb 01.
Article in English | MEDLINE | ID: mdl-18241108

ABSTRACT

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.


Subject(s)
Cat Diseases/drug therapy , Chlorambucil/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/veterinary , Prednisone/therapeutic use , Remission Induction , Animals , Antineoplastic Agents, Alkylating/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Cat Diseases/mortality , Cat Diseases/pathology , Cats , Female , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Prognosis , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
19.
J Am Vet Med Assoc ; 231(9): 1354-60, 2007 Nov 01.
Article in English | MEDLINE | ID: mdl-17975994

ABSTRACT

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.


Subject(s)
Antineoplastic Agents/administration & dosage , Catheters, Indwelling/veterinary , Femoral Vein , Veterinary Medicine/instrumentation , Veterinary Medicine/methods , Animals , Cat Diseases/drug therapy , Catheters, Indwelling/adverse effects , Catheters, Indwelling/standards , Cats , Dog Diseases/drug therapy , Dogs , Female , Male , Neoplasms/drug therapy , Neoplasms/veterinary , Prospective Studies , Time Factors
20.
J Vet Intern Med ; 21(5): 1041-7, 2007.
Article in English | MEDLINE | ID: mdl-17939562

ABSTRACT

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.


Subject(s)
Dog Diseases/pathology , Lymphoma/veterinary , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Blood Cell Count/veterinary , Bone Marrow Cells/pathology , Dog Diseases/drug therapy , Dogs , Doxorubicin/administration & dosage , Female , Lymphoma/drug therapy , Lymphoma/pathology , Male , Neoplasm Staging/methods , Neoplasm Staging/veterinary , Prospective Studies , Radiography, Abdominal/veterinary , Radiography, Thoracic/veterinary , Treatment Outcome , Ultrasonography/veterinary
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