Phase I dose escalation of single-agent vinblastine in dogs.

Full Abstract

BACKGROUND: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. HYPOTHESIS: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. ANIMALS: Twenty-three dogs with lymphoma or cutaneous mast cell tumors. METHODS: Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2-3 weeks. RESULTS: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.

Author information

Author/s: Bailey, D B (DB); Rassnick, K M (KM); Kristal, O (O); Chretin, J D (JD); Balkman, C E (CE);

Affiliation: Department of Clinical Sciences, Sprecher Institute for Comparative Cancer Research, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. dbb3(-atsign-)cornell.edu

Journal and publication information

Publication Type: Clinical Trial, Phase I; Journal Article

Journal: Journal of veterinary internal medicine / American College of Veterinary Internal Medicine (J Vet Intern Med), published in United States. (Language: eng)

Reference: -2008 Nov-Dec; vol 22 (issue 6) : pp 1397-402

Dates: Created 2008/11/12; Completed 2008/12/19;

PMID: 19000250, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

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