title: Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Naïve Canine Multicentric Lymphoma.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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/m2IV 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
  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.
authors.affiliation: Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Fort Collins, CO.|Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, CO.|Developmental Therapeutics Program, Comprehensive Cancer Center, University of Colorado, Aurora, CO.
authors.forename: D H
authors.identifier: http://orcid.org/0000-0002-8914-7767
authors.initials: DH
authors.lastname: Thamm
authors.affiliation: School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI.
authors.forename: D M
authors.initials: DM
authors.lastname: Vail
authors.affiliation: The Veterinary Cancer Center, Norwalk, CT.
authors.forename: G S
authors.initials: GS
authors.lastname: Post
authors.affiliation: College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL.
authors.forename: T M
authors.initials: TM
authors.lastname: Fan
authors.affiliation: Veterinary Specialty Hospital of San Diego, San Diego, CA.
authors.forename: B S
authors.initials: BS
authors.lastname: Phillips
authors.affiliation: College of Veterinary Medicine, University of Missouri, Columbia, MO.
authors.forename: S
authors.initials: S
authors.lastname: Axiak-Bechtel
authors.affiliation: Veterinary Referral Center of Colorado, Englewood, CO.
authors.forename: R S
authors.initials: RS
authors.lastname: Elmslie
authors.affiliation: Southern Arizona Veterinary Specialty and Emergency Center, Tucson, AZ.
authors.forename: M K
authors.initials: MK
authors.lastname: Klein
authors.affiliation: Veterinary Specialty Hospital of the Carolinas, Cary, NC.
authors.forename: D A
authors.initials: DA
authors.lastname: Ruslander
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011355:Prodrugs; D011687:Purines; C531423:rabacfosadine; D004317:Doxorubicin; D000409:Alanine
keywords: Chemotherapy; Dog; Guanine; Lymphosarcoma