| Abstract | 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/m(2) of body surface area, IV, and dosages were increased by 50 to 100 mg/m(2) 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/m(2), 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/m(2) every 3 weeks. This dosage should be used in phase II clinical trials. |
| Authors | Kenneth M Rassnick, Antony S Moore, Nicole C Northrup, Orna Kristal, Bernard B Beaulieu, Lionel D Lewis, Rodney L Page
(Affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.)
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| Journal | American journal of veterinary research
(Am J Vet Res)
Vol. 67
Issue 3
Pg. 510-6
(Mar 2006)
ISSN: 0002-9645 United States |
| PMID | 16506919
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Antineoplastic Agents, Alkylating
- Ifosfamide
|
| Topics |
- Animals
- Antineoplastic Agents, Alkylating
(adverse effects, chemistry, pharmacokinetics, therapeutic use)
- Area Under Curve
- Cat Diseases
(drug therapy)
- Cats
- Dose-Response Relationship, Drug
- Female
- Half-Life
- Ifosfamide
(adverse effects, chemistry, pharmacokinetics, therapeutic use)
- Male
- Models, Chemical
- Molecular Structure
- Sarcoma
(drug therapy, veterinary)
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