Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Naïve Canine Multicentric Lymphoma

D. H. Thamm, D. M. Vail, G. S. Post, T. M. Fan, B. S. Phillips, S. Axiak-Bechtel, R. S. Elmslie, M. K. Klein, D. A. Ruslander

Research output: Contribution to journalArticle

Abstract

Background: Standard of care treatment for multicentric lymphoma in dogs remains doxorubicin (DOX)-based combination chemotherapy, but owners may hesitate to commit the time and financial resources to complete such a protocol, typically requiring 12–16 visits. Rabacfosadine (RAB), a double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine, has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than DOX. Hypothesis/Objectives: Our objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma. Animals: Fifty-four dogs with previously untreated lymphoma. Methods: Open-label, multicenter prospective clinical trial. Dogs received alternating RAB (1.0 mg/kg IV weeks 0, 6, 12) and DOX (30 mg/m2 IV weeks 3, 9, 15). Dogs that achieved complete response (CR) were followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and AEs were performed every 21 days. Results: The overall response rate was 84% (68%; CR; 16%; partial response [PR)]. The overall median progression-free interval (PFI) was 194 days (216 for CR and 63 for PR). Most AEs were mild and self-limiting: gastrointestinal and hematologic AEs were most common. Thirteen dogs experienced dermatologic AEs, and 2 dogs developed grade 5 pulmonary fibrosis. Conclusions and Clinical Importance: Alternating RAB/DOX generally was well tolerated and resulted in PFIs comparable to standard DOX-based multi-agent protocols, with fewer treatment visits. Most adverse events were mild or moderate and self-limiting. Further studies are warranted to explore long-term outcome and other RAB chemotherapy combinations.

Original languageEnglish (US)
Pages (from-to)872-878
Number of pages7
JournalJournal of veterinary internal medicine
Volume31
Issue number3
DOIs
StatePublished - May 1 2017

Keywords

  • Chemotherapy
  • Dog
  • Guanine
  • Lymphosarcoma

ASJC Scopus subject areas

  • veterinary(all)

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    Thamm, D. H., Vail, D. M., Post, G. S., Fan, T. M., Phillips, B. S., Axiak-Bechtel, S., Elmslie, R. S., Klein, M. K., & Ruslander, D. A. (2017). Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Naïve Canine Multicentric Lymphoma. Journal of veterinary internal medicine, 31(3), 872-878. https://doi.org/10.1111/jvim.14700