A Novel Treatment Option For Canine Lymphoma
Rebeca Risbon, VMD, DACVIM (oncology)
Veterinary Specialty & Emergency Center
Lymphoma is the most common canine hematopoietic neoplasm with an annual incidence estimated at 13-24 per 100,000 dogs at risk while age specific incidences can be as high as 84 per 100,000 dogs aged 10-11 years.
Without therapeutic intervention, most dogs will succumb to their disease within 4-6 weeks of diagnosis. The present standard of care for canine lymphoma consists of multiagent systemic chemotherapy combinations.
Despite the fact that lymphoma represents 80% of all canine hematopoietic neoplasia, very few improvements in response rate or survival times have been made by changing the scheduling of CHOP based chemotherapy protocols (cyclophosphamide, doxorubicin, vincristine, and prednisone). The approximate response rate remains at 70-90% with a 1-year survival rate of 30-50% being common depending on stage/substage of disease, histopathologic findings, and immunophenotype. Ultimately, 90% of dogs that achieve remission will relapse and with limited options for reinduction chemotherapy, the long-term survival and cure rates for dogs with lymphoma remain poor. This results in an unmet need in our treatment arsenal for novel agents with improved efficacy, especially for canine patients that have already received and failed first line therapy.
In January of 2017, the FDA released conditional approval for TanoveaTM-CA1 (rabacfosadine) as a treatment for canine lymphoma and the drug first became available for purchase in April 2017. Rabacfosadine is a small molecule prodrug that inhibits DNA proliferation of lymphocytes in vitro and specifically loads in lymphoid and myeloid cells in vivo rendering it an ideal candidate for the treatment of lymphoma.
Treatment Schedule and Efficacy
In the initial pilot study, 38 dogs with lymphoma were evaluated for the optimal dose scheduling, remission rate, and remission duration. For treatment naïve dogs, there was a 100% response rate and a 62% response rate for dogs that had previously failed chemotherapy. The approximate median remission duration was 128 days and 43-99 days for treatment naïve dogs and relapsed dogs, respectively. Not surprisingly, the response duration for B cell lymphoma was superior to that seen for T cell lymphoma (132 days and 19 da, respectively). ysTanoveaTM-CA1 is given IV once every 21 days and can be used up to 5 times if effective. Because it is presently conditionally approved, this means that we can only use it according to the specific label recommendations.
The most common side effects of TanoveaTM-CA1 are gastrointestinal (anorexia/weight loss) and hematologic (neutropenia) in nature. However, there are 2 unique side effects documented with this drug that are not typically seen with other standard chemotherapy agents: dermatopathy and pulmonary dysfunction. Approximately 37% of treated dogs developed dermatopathy that was self-limiting, resolved with supportive care/treatment delay, and did not recur with reinstitution of therapy. Mild cases consisted of local superficial erythematous lesions that were often pruritic and most often localized to the ear canal and/or as small foci on the back or inguinal areas. In more severe cases the lesions were more extensive, became exudative, and had bullae formation. Pulmonary dysfunction was identified in 7-8% of dogs treated with TanoveaTM-CA1. Clinically, this manifests at tachypnea and dyspnea with radiographic evidence of pulmonary fibrosis. For this reason, TanoveaTM-CA1 is contraindicated in West Highland White Terriers due to the established breed associated risk for the development of pulmonary fibrosis. Caution is recommended when using the drug in other Terrier breeds and in dogs with existing chronic airway disease.
Recommendations For Use
To date, TanoveaTM-CA1 has been investigated in at least nine clinical studies evaluating its efficacy in dogs with lymphoma with additional studies currently ongoing. There is currently no consensus statement amongst veterinary oncologists regarding when to recommend TanoveaTM-CA1 or when to incorporate it into standard CHOP based therapy for lymphoma. However, continuing education seminars are available and direct communication with the principle investigators has been crucial in disseminating an understanding of this drug’s potential among veterinary oncologists. Most interesting is the potential combination of TanoveaTM-CA1 and doxorubicin as these drugs have non-overlapping toxicities and different mechanisms of action. Research data on this drug combination has been presented in abstract form at the ACVIM Forum in 2016 and initial results suggest a similar remission duration and survival time when compared to CHOP based therapies. Based on the current information available, TanoveaTM-CA1 appears to be most efficacious when used as a first line or first choice for a patient with relapsed lymphoma. The incorporation into current standard of care protocols remains interesting and we are expecting additional studies to be forthcoming.
If you have any questions about TanoveaTM-CA1 in general, or to discuss a specific case that may be appropriate for treatment with TanoveaTM-CA1, please call Dr. Rebecca Risbon at 215-750-7884 or 215-752-3463 (Referring Vet Direct Line).
Dr. Rebecca Risbon is a board-certified oncology specialist at the Veterinary Specialty & Emergency Center. The Veterinary Specialty & Emergency Center operates state-of the-art emergency and specialty veterinary hospitals that are open 24/7/365 in Levittown PA, Philadelphia PA and Conshohocken PA. For more information about our world-class emergency and specialty care, please visit VSEC on the web at www.VSECVET.com.