Phase I trial and pharmacokinetic analysis of ifosfamide in cats with sarcomas.

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
• Journal: American journal of veterinary research (Am J Vet Res) Vol. 67 Issue 3 Pg. 510-6 (Mar 2006) ISSN: 0002-9645 [Print] United States
• PMID: 16506919 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

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)