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

  • J Vet Intern Med. 2017 May;31(3):872-878. doi: 10.1111/jvim.14700.
D H Thamm  1  2  3 ,  D M Vail  4 ,  G S Post  5 ,  T M Fan  6 ,  B S Phillips  7 ,  S Axiak-Bechtel  8 ,  R S Elmslie  9 ,  M K Klein  10 ,  D A Ruslander  11
Affiliations
  • 1. Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Fort Collins, CO.
  • 2. Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, CO.
  • 3. Developmental Therapeutics Program, Comprehensive Cancer Center, University of Colorado, Aurora, CO.
  • 4. School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI.
  • 5. The Veterinary Cancer Center, Norwalk, CT.
  • 6. College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL.
  • 7. Veterinary Specialty Hospital of San Diego, San Diego, CA.
  • 8. College of Veterinary Medicine, University of Missouri, Columbia, MO.
  • 9. Veterinary Referral Center of Colorado, Englewood, CO.
  • 10. Southern Arizona Veterinary Specialty and Emergency Center, Tucson, AZ.
  • 11. Veterinary Specialty Hospital of the Carolinas, Cary, NC.
PMID: 28370378 DOI: 10.1111/jvim.14700
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.

Keywords
Chemotherapy; Dog; Guanine; Lymphosarcoma.
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