Extremely high exposures in an obese patient receiving high-dose cyclophosphamide,thiotepa and carboplatin

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 microg/m(2). 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 microg/m(2). 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.