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 determine the efficacy of strontium 90 β irradiation in the management of cutaneous mast cell tumors (CMCTs) in cats.
Study Design—Retrospective case series.
Animals—35 client-owned cats with CMCTs.
Procedure—Medical records of cats with CMCTs in which tumors were radiated by use of a strontium 90 ophthalmic applicator from 1992 to 2002 were reviewed. Cats were included if CMCT was diagnosed, there were no other sites of MCT involvement at the time of treatment, and records contained adequate follow-up information to permit retrospective assessment of local tumor control.
Results—54 tumors in 35 cats were treated with a median dose of 135 Gy of strontium 90 β irradiation, resulting in local tumor control in 53 of 54 (98%) tumors with a median follow-up time of 783 days after treatment. Median survival time was 1,075 days. Adverse effects of treatment appeared to be infrequent and of mild severity.
Conclusions and Clinical Relevance—Results indicated that strontium 90 β irradiation resulted in long-term tumor control and should be considered an effective alternative to surgical resection in management of CMCTs in cats.
Objective—To determine outcome for dogs with nonresectable thyroid carcinomas treated with sodium iodide I 131 and identify factors associated with outcome.
Design—Retrospective case series.
Procedures—A definitive or presumptive diagnosis of thyroid tumor was made on the basis of cytologic or histologic examination, abnormal accumulation of sodium pertechnetate Tc 99m during scintigraphy, or both, and dogs were treated with sodium iodide I 131. Dogs with cervical thyroid tumors were evaluated 3 to 6 weeks after 131I therapy, and residual tumor was resected when feasible.
Results—Prior to 131I therapy, 32 dogs had a solitary mass and 7 had metastases; 21 were hyperthyroid, 16 were euthyroid, and 2 were hypothyroid. Median survival time for dogs with local or regional tumors (ie, stage II or III) was significantly longer (839 days) than median survival time for dogs with metastasis (366 days). Tumor site (cervical vs ectopic), dose of sodium iodide I 131, age, body weight, treatment (131I therapy alone vs 131I therapy followed by surgery), and serum T4 concentration prior to 131I therapy were not significantly associated with survival time. Three dogs died of radioiodine-associated myelosuppression within 3 months after treatment, but no specific factor associated with development of toxicosis was identified.
Conclusions and Clinical Relevance—Results suggested that 131I therapy may result in prolonged survival times in dogs with nonresectable thyroid tumors, regardless of serum thyroxine concentration prior to treatment. Dogs undergoing 131I therapy should be monitored for signs of bone marrow suppression.
Objective—To determine clinical activity and toxic effects of ifosfamide when used to treat cats with vaccine-associated sarcoma (VAS).
Animals—27 cats with a nonresectable, recurrent, or metastatic VAS.
Procedure—Each cat received ifosfamide (900 mg/m2 of body surface area) as an IV infusion during a 30-minute period. Diuresis by infusion of saline (0.9% NaCl) solution and administration of mesna were used to prevent urothelial toxicosis. Treatments were administered every 3 weeks, and tumor response was assessed after the second treatment. All ifos-famide-associated toxic effects were graded in accordance with predetermined criteria.
Results—61 treatments were administered to 27 cats (median, 2 treatments/cat; range, 1 to 4 treat-ments/cat). After ifosfamide treatment, 1 cat had a complete response and 10 had partial responses for an overall response rate of 11 of 27 (41%; 95% confidence interval [CI], 25% to 59%). Responses lasted from 21 to 133 days (median, 70 days; 95% CI, 60 to 113 days). The acute dose-limiting toxicosis was neutropenia, which was detected 5 to 28 days (median, 7 days) after treatment. Median nadir neutrophil count was 1,600 cells/μL (range, 200 to 5,382 cells/μL). Nine (33%) cats had adverse gastrointestinal effects (primarily salivation during the ifosfamide infusion and inappetence after treatment). Two cats were euthanatized because of severe nephrotoxicosis, and 1 cat developed pulmonary edema during diuresis.
Conclusions and Clinical Relevance—Ifosfamide has antitumor activity against VAS in cats and is tolerated well by most cats. Ifosfamide should be evaluated as an adjuvant treatment for cats with VAS.
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 the maximally tolerated dose (MTD) and dose-limiting toxicosis (DLT) of ifosfamide in tumor-bearing cats.
Animals—38 cats with resected, recurrent, or metastatic sarcomas.
Procedure—The starting dosage of ifosfamide was 400 mg/m2 of body surface area, IV, and dosages were increased by 50 to 100 mg/m2 in cohorts of 3 cats. To protect against urotoxicosis, mesna was administered at a dosage equal to 20% of the calculated ifosfamide dosage. Diuresis with saline (0.9% NaCl) solution before and after administration of ifosfamide was used to minimize nephrotoxicosis. Samples for pharmacokinetic analysis were obtained after the MTD was reached.
Results—38 cats were entered into this phase I study and were administered a single dose of ifosfamide at various dosages. The MTD was 1,000 mg/m2, and neutropenia was the DLT. Seven of 8 episodes of neutropenia were on day 7 after treatment, and 1 cat developed severe neutropenia on day 5. Adverse effects on the gastrointestinal tract were generally mild and self-limiting, the most common of which was nausea during ifosfamide infusion. One cat had signs consistent with a drug-induced hypersensitivity reaction. There were no episodes of hemorrhagic cystitis or nephrotoxicosis. Correlations between pharmacokinetic variables and ifosfamide-associated toxicoses were not found. Preliminary evidence of antitumor activity was observed in 6 of 27 cats with measurable tumors.
Conclusions and Clinical Relevance—The dosage of ifosfamide recommended to treat tumor-bearing cats is 900 mg/m2 every 3 weeks. This dosage should be used in phase II clinical trials.