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


OBJECTIVE
The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2.


METHODS
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
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.
Bailey
D B
DB
Department of Clinical Sciences, Sprecher Institute for Comparative Cancer Research, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. dbb3@cornell.edu
Rassnick
K M
KM
Kristal
O
O
Chretin
J D
JD
Balkman
C E
CE
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D014747:Vinblastine / Q000008:administration & dosage* / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014747:Vinblastine