Comparative oncology has shown that naturally occurring canine
cancers are of valuable and translatable interest for the understanding of human
cancer biology and the characterization of new
therapies. This work was part of a comparative oncology project assessing a new, clinical-stage
topoisomerase II inhibitor and comparing it with
etoposide in dogs with spontaneous
lymphoma with the objective to translate findings from dogs to humans.
Etoposide is a
topoisomerase II inhibitor widely used in various humans' solid and hematopoietic
cancer, but little data is available concerning its potential antitumor efficacy in dogs.
Etoposide phosphate is a water-soluble
prodrug of
etoposide which is expected to be better tolerated in dogs. The objectives of this study were to assess the safety, the tolerability and the efficacy of intravenous
etoposide phosphate in dogs with multicentric
lymphoma. Seven dose levels were evaluated in a traditional 3+3 phase I design. Twenty-seven owned-dogs with high-grade multicentric
lymphoma were enrolled and treated with three cycles of
etoposide phosphate IV
injections every 2 weeks. Adverse effects were graded according to the Veterinary Cooperative Oncology Group criteria. A complete end-staging was realized 45 days after inclusion. The maximal tolerated dose was 300 mg/m2. At this dose level, the overall response rate was 83.3% (n = 6, 3 PR and 2 CR). Only a moderate reversible gastrointestinal toxicity, no severe myelotoxicity and no
hypersensitivity reaction were reported at this dose level. Beyond the characterization of
etoposide clinical efficacy in dogs, this study underlined the clinical and therapeutic homologies between dog and human
lymphomas.