Preclinical study of dolastatin-10 in dogs with spontaneous neoplasia

Douglas H. Thamm, Gregory E. MacEwen, Brenda S. Phillips, Elizabeth A. Hershey, Kristine M. Burgess, George Pettit, David M. Vail

Research output: Contribution to journalReview articlepeer-review

16 Scopus citations

Abstract

Purpose: To evaluate the short-term adverse effects of administration of dolastatin-10 (Dol-10) to dogs with spontaneously occurring malignant tumors. Methods: A total of 34 tumor-bearing dogs were given Dol-10 as a rapid intravenous bolus every 14 days at starting dosages ranging from 200 to 350 μg/m2. Acute and short-term adverse effects, antitumor response, and duration of response were characterized. Results: The maximum tolerated dose varied greatly from patient to patient, but a reasonable starting dose for further studies was established at 300 μg/m2. The median number of treatments per dog was 2 (range 1 to 17). Granulocytopenia was the dose-limiting toxicity. The overall response rate was 3%, consisting of a complete and durable (30 months) response in a dog with high-grade malignant lymphoma that was refractory to standard therapy. Two minor or transient responses were observed, and two dogs experienced disease stabilization for 8 and 16 weeks. Conclusions: Dol-10 appears to be well tolerated in tumor-bearing dogs at doses approaching those tolerated by humans. The clinical activity observed in dogs with non-Hodgkin's lymphoma warrants further investigation.

Original languageEnglish (US)
Pages (from-to)251-255
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume49
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Dogs
  • Dolastatin-10
  • Spontaneous neoplasia

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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