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.
Objective—To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUCTarget) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUCTarget.
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 = AUCTarget × 2.6 × GFR × body weight. Initial AUCTarget 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 ≥ 4 weeks. Following identification of the maximum tolerated AUCTarget, additional cats were treated at that AUCTarget and plasma platinum concentrations were measured in 6 cats.
Results—The AUCTarget values ranged from 2.0 to 3.0 min·mg·mL−1. Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUCTarget 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/μL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUCTarget 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 AUCTarget for a single dose of carboplatin was 2.75 min·mg·mL−1.
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.
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 (99mTc-DTPA) to yield GFR99mTc-DTPA and serum clearance of iohexol to yield GFRIohexol. 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 (AUCTarget) and estimation of platinum clearance (CLPT) derived from GFR99mTc-DTPA as follows: dose = AUCTarget × 2.6 × GFR99mTc-DTPA × body weight, where AUCTarget is 2.75 min·mg·mL−1. Plasma platinum concentrations were measured via atomic absorption spectrophotometry. Values for GFR99mTc-DTPA and GFRIohexol were compared by use of least-squares regression and Bland-Altman analysis. Least-squares regression was used to determine whether CLPT could be predicted from GFR99mTc-DTPA or GFRIohexol (or both).
Results—GFR99mTc-DTPA and GFRIohexol were strongly correlated (r = 0.90), but GFRIohexol values were significantly larger by a factor of approximately 1.4. Platinum clearance had a significant linear relationship to GFR99mTc-DTPA (CLPT = 2.5 × GFR99mTc-DTPA) and to GFRIohexol (CLPT = [1.3 × GFRIohexol] + 1.4).
Conclusions and Clinical Relevance—In cats, serum iohexol clearance was an accurate predictor of CLPT and can be used to calculate the carboplatin dose as follows: dose = AUCTarget × ([1.3 × GFRIohexol] + 1.4) × body weight.
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.
Objective—To compare clinical outcome of dogs
with cutaneous mast cell tumors (MCTs) in the
inguinal or perineal region with outcome for dogs with
MCTs in other cutaneous locations.
Animals—37 dogs with MCTs in the inguinal or perineal
region and 87 dogs with MCTs in other cutaneous
Procedure—Information obtained from the medical
records included sex, breed, age, histologic grade of
all tumors, number and location of all tumors, tumor
size (ie, diameter of the tumor), completeness of surgical
excision, treatments administered in addition to
surgery, and outcome. In all dogs, the primary treatment
consisted of surgical excision.
Results—Disease-free interval and survival time for
dogs with MCTs in the inguinal or perineal region were
not significantly different from values for dogs with
MCTs in other cutaneous locations. Dogs with incompletely
excised tumors, dogs with grade III tumors, and
dogs that received systemic treatment were 2, 2.5,
and 4 times as likely, respectively, to have a relapse.
Factors significantly associated with a shorter survival
time were age > 8 years, metastatic disease at the
time of initial diagnosis, and tumor relapse.
Conclusions and Clinical Relevance—Results of the
present study suggest that dogs with MCTs in the
inguinal or perineal region do not have a worse prognosis
in regard to disease-free interval or survival time
than do dogs with MCTs in other cutaneous locations.
Treatment recommendations for dogs with cutaneous
MCTs should be based on confirmed predictors of biological
behavior, such as histologic grade and clinical
stage. (J Am Vet Med Assoc 2005;226:1368–1374)
Objective—To characterize the pharmacokinetic disposition
of carboplatin and determine whether
glomerular filtration rate (GFR) could be used to predict
carboplatin clearance and myelotoxic effects in
cats with tumors.
Animals—10 cats with tumors.
Procedure—Glomerular filtration rate was assessed
in each cat by monitoring plasma clearance of technetium
Tc 99m-labeled diethylenetriaminepentaacetic
acid (99mTc-DTPA). Each cat received carboplatin (200
mg/m2 of body surface area) administered as an IV
bolus. Plasma platinum concentrations were measured
via atomic absorption spectrophotometry, and
pharmacokinetic analysis was performed. A CBC was
performed weekly for each cat, and the correlation
between the area under the concentration-versus-time
curve (AUC) and the severity of myelosuppression
was calculated. Least squares regression analysis
was performed to determine whether GFR could
be used to predict plasma platinum clearance (ClPt).
Results—For all cats, AUC measurements ranged
from 0.99 to 4.30 min·mg·mL–1. Neutrophil concentration
nadirs were detected 1 to 3 weeks after
treatment and ranged from 200 to 8,000 cells/µL.
The absolute neutrophil concentration at the nadir
was inversely correlated with AUC. The ClPt was predicted
by use of GFR measurements (ClPt = 2.60 ×
GFR). A carboplatin dose prescription model was
derived involving AUC, estimated ClPt, and body
weight in kilograms (BWkg), in which dose = AUC ×
2.60(GFR) × BWkg.
Conclusions and Clinical Relevance—In cats, an
individualized prescription strategy for carboplatin
administration based on a targeted AUC and determination
of GFR might more uniformly predict myelosuppression
than that predicted by conventional dosing
based on body surface area. (Am J Vet Res 2004;65:1502–1507)
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.
Objective—To determine the maximum tolerated dose and characterize the pharmacokinetic disposition of an orally administered combination of docetaxel and cyclosporin A (CSA) in dogs with tumors.
Animals—16 client-owned dogs with metastatic or advanced-stage refractory tumors.
Procedures—An open-label, dose-escalation, singledose, phase I study of docetaxel administered in combination with a fixed dose of CSA was conducted. Docetaxel (at doses of 1.5, 1.625, or 1.75 mg/kg) and CSA (5 mg/kg) were administered concurrently via gavage twice during a 3-week period. Plasma docetaxel concentrations were quantified by use of high-performance liquid chromatography, and pharmacokinetic disposition was characterized by use of noncompartmental analysis. Dogs' clinical signs and results of hematologic and biochemical analyses were monitored for evidence of toxicosis.
Results—No acute hypersensitivity reactions were observed after oral administration of docetaxel. Disposition of docetaxel was dose independent over the range evaluated, and pharmacokinetic variables were similar to those reported in previous studies involving healthy dogs, with the exception that values for clearance were significantly higher in the dogs reported here. The maximum tolerated dose of docetaxel was 1.625 mg/kg. Gastrointestinal signs of toxicosis were dose limiting.
Conclusions and Clinical Relevance—The absence of myelosuppression suggested that the docetaxelCSA combination may be administered more frequently than the schedule used. Further studies are warranted to evaluate combination treatment administered on a biweekly schedule in dogs with epithelial tumors.
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 ≥ 50 mg/m2.
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/m2 in 22 cats and 60 mg/m2 in 16 cats. Median administered dosage of lomustine was 56 mg/m2 (range, 48 to 65 mg/m2), 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.