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

Abstract

BackgroundStandard 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/ObjectivesOur objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma.AnimalsFifty‐four dogs with previously untreated lymphoma.MethodsOpen‐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.ResultsThe 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 ImportanceAlternating 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.

Concurrent use of rabacfosadine and L‐asparaginase for relapsed or refractory multicentric lymphoma in dogs

“…In this study, as is consistent with previous RAB studies, dogs with T‐cell lymphoma had a shorter median progression‐free interval (MPFI) than dogs with B‐cell lymphoma (63 days for B‐cells, 43 days for T‐cells). The ORR for dogs with T‐cell lymphoma was 62.5%, with 12.5% achieving a CR.…”

“…Alternatively, previous che- which might activate pro-survival pathways. 19,20 In this study, as is consistent with previous RAB studies, 17 The schedule for L-ASP administration in this current study was based on protocols combining L-ASP with CCNU. Two such protocols have been evaluated in the literature for relapsed lymphoma in dogs.…”

“…The MPFS for all dogs was 63 days, and 144 days for dogs achieving a CR. The majority of AEs seen in this study population were self‐limiting, and similar in frequency/severity to previously reported studies evaluating RAB . Five dogs were withdrawn from the study because of AEs, and the majority of these were caused by grade 3 hyporexia/weight loss.…”

“…The ORR for dogs with T‐cell lymphoma was 62.5%, with 12.5% achieving a CR. Reported response rates for naïve and refractory T‐cell lymphoma treated with RAB range from 25 to 56% . The progression‐free interval in this study for T‐cell lymphomas was similar to slightly improved from what has been reported previously; however, any conclusions regarding superiority of RAB combined with L‐ASP cannot be drawn from this study.…”

“…The majority of AEs seen in this study population were self-limiting, and similar in frequency/severity to previously reported studies evaluating RAB. 4,17 Five dogs were withdrawn from the study because of AEs, and the majority of these were caused by grade 3 hyporexia/weight loss. Of these 5 dogs, 2 of them had a 20% dose reduction of RAB but were later withdrawn because of continued AEs.…”