{"id":30751,"date":"2022-04-12T16:54:26","date_gmt":"2022-04-12T16:54:26","guid":{"rendered":"https:\/\/todaysveterinarypractice.com\/?p=30751"},"modified":"2022-07-13T18:16:32","modified_gmt":"2022-07-13T18:16:32","slug":"new-cancer-treatments-for-dogs","status":"publish","type":"post","link":"https:\/\/navc.sitepreview.app\/todaysveterinarypractice.com\/pharmacology\/new-cancer-treatments-for-dogs\/","title":{"rendered":"What You Need to Know About New Cancer Treatments for Dogs"},"content":{"rendered":"

The growing number of specialized oncology therapeutics available for dogs (<\/span>TABLE 1<\/span><\/strong>) makes remaining current on the latest advances challenging, especially in general practice. Primary care veterinarians routinely diagnose cancer and often initiate client discussions regarding treatment options. Keeping up to date on current cancer treatments is important for presenting the latest in case management options to clients.<\/span><\/p>\n

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This article reviews the status, science, available key supporting data, and clinical use of several canine cancer therapeutics; however, no consensus guidelines on use of these agents currently exist. Do not hesitate to consult a board-certified veterinary oncologist regarding case selection advice when considering these treatment options for patients.<\/span><\/p>\n

Lymphoma<\/h2>\n

Tanovea (rabacfosadine for injection)<\/h3>\n

Approval status: <\/b>U.S. Food and Drug Administration (FDA) approved (2021)<\/span><\/p>\n

Manufacturer: <\/b>Elanco (Greenfield, Indiana)<\/span><\/p>\n

Mechanism of action: <\/b>Rabacfosadine is a prodrug of the nucleotide analogue 9-(2-phosphonylmethoxyethyl) guanine (PMEG), which interferes with DNA synthesis. It effectively loads lymphoid cells while reducing levels of PMEG in plasma and target organs of toxicity.1,2<\/sup><\/span><\/p>\n

Indication: <\/b>Tanovea is labeled for the treatment of lymphoma in dogs.1<\/sup> Off-label use in dogs with multiple myeloma has also been reported.<\/span><\/p>\n

Handling: <\/b>Chemotherapy-resistant gloves, goggles, and protective clothing should be worn when handling or administering Tanovea. Refer to the Occupational Safety and Health Administration (OSHA) for appropriate guidelines (osha.gov\/hazardous-drugs\/controlling-occex<\/span><\/a>). See the package insert for the full list of warnings.1<\/sup><\/span><\/p>\n

Administration: <\/b>Tanovea is administered at a dose of 1\u00a0mg\/kg via 30-minute IV infusion once every 3 weeks for up to 5 treatments. Stepwise dose decreases (to 0.8\u00a0mg\/kg, 0.66 mg\/kg) or dose delays may be used to manage adverse events.1<\/sup>\u00a0<\/span><\/span><\/p>\n

Key clinical data: <\/b>The pivotal clinical trial enrolled 158 dogs with na\u00efve (untreated) or previously treated (relapsed) lymphoma; 128 received Tanovea and 30\u00a0received placebo. The overall response rate (ORR) in all dogs was 73%; median progression-free survival was 82 days for all dogs and 151 days for dogs that responded. Dogs with B-cell lymphoma and those na\u00efve to treatment responded better.1<\/sup> One recent publication summarizing 3 separate studies in dogs with na\u00efve lymphoma treated with Tanovea with or without prednisone showed an ORR of 87% and progression-free interval of 122 days.3<\/sup> Additional studies have reported response in dogs with na\u00efve lymphoma treated with an alternating Tanovea\/doxorubicin protocol2<\/sup> and dogs with previously treated lymphoma receiving Tanovea as a rescue therapy.4,5<\/sup><\/span><\/p>\n

Most common side effects: <\/b>Similar to other cytotoxic chemotherapeutics, the most commonly noted adverse effects include gastrointestinal signs (e.g., diarrhea, decreased appetite\/anorexia, emesis, weight loss) and myelosuppression (neutropenia).1<\/sup> One important potential toxicosis is the development of pulmonary fibrosis, which may be life-threatening, in approximately 5% of dogs. Based on the risk of this adverse event, Tanovea should not be used in West Highland White terriers and should be used with caution in other terrier breeds.1-3<\/sup> Clients should be advised of this potentially fatal complication and monitoring (via serial thoracic radiographs) should be considered. Dermatopathies (e.g., otitis, alopecia, dermatitis, erythema, pruritis, hyperpigmentation, skin ulcerations, bacterial skin infections) are seen in 20% to more than 50% of dogs.1-3<\/sup><\/span><\/p>\n

Clinical use: <\/b>Current treatment considerations include use as single-agent therapy (with prednisone), in combination with multiagent chemotherapy protocols (potentially replacing doxorubicin in some versions of CHOP-based protocol [i.e., cyclophosphamide, doxorubicin, vincristine sulfate, prednisone]), or in an alternating Tanovea\/doxorubicin protocol (1 drug given once every 3 weeks for a total of 3 treatments of each drug, 6 treatments total) in dogs with na\u00efve or previously treated lymphoma.<\/span><\/p>\n

Laverdia-CA1 (verdinexor tablets)<\/h3>\n

Approval status: <\/b>FDA conditional approval (2021)<\/span><\/p>\n

Manufacturer: <\/b>Dechra Veterinary Products (Overland Park, Kansas)<\/span><\/p>\n

Mechanism of action: <\/b>Laverdia-CA1 is a selective inhibitor of nuclear export that blocks <\/b>exportin 1 (XPO1 or chromosome region maintenance protein 1), a regulatory protein responsible for exporting several tumor suppressor and growth regulatory proteins from the nucleus to the cytoplasm. By keeping these regulatory proteins within the nucleus, Laverdia-CA1 may help treat several types of cancer.6<\/sup><\/span><\/p>\n

Indication: <\/b>Laverdia-CA1 is labeled for the treatment of lymphoma in dogs.7<\/sup><\/span><\/p>\n

Handling: <\/b>Disposable chemotherapy-resistant gloves should be worn when handling tablets.7<\/sup><\/span><\/p>\n

Administration:<\/b> Initial starting dosage is 1.25 mg\/kg PO twice per week (e.g., Monday and Thursday) with at least 72 hours between doses. Laverdia-CA1 should be administered with food. After 2 weeks, a dosage increase to 1.5 mg\/kg twice per week can be considered,7<\/sup> depending on how well the drug is tolerated and patient response to therapy.<\/span><\/p>\n

Key clinical data: <\/b>In consideration for reasonable expectation of effectiveness, 58 dogs with lymphoma treated with Laverdia-CA1 (39 dogs also received prednisone) were evaluated. The ORR (those in complete or partial response) was 34.5%, with a median duration of response of 18 days (range, 7 to 187 days). The median time to tumor progression (TTP) in all dogs was 29.5 days (range, 7 to 244 days). A subset of dogs (n = 17; 29%) had TTP of at least 56 days.6-8<\/sup><\/span><\/p>\n

Most common side effects: <\/b>Anorexia, vomiting, diarrhea, weight loss, and lethargy were the most common adverse events noted.7<\/sup> Most were mild to moderate in nature and treated with supportive care as clinically indicated.6,8<\/sup><\/span><\/p>\n

Clinical use: <\/b>Best clinical use will be more fully defined through additional prospective, randomized studies. Current treatment considerations include use as single-agent therapy (with prednisone), in combination with multiagent chemotherapy protocols, and\/or as maintenance therapy after completion of multiagent chemotherapy protocols in dogs with na\u00efve or previously treated lymphoma.<\/span><\/p>\n

Mast Cell Tumors<\/h2>\n

Stelfonta (tigilanol tiglate injection)<\/h3>\n

Approval status: <\/b>FDA approved (2020)<\/span><\/p>\n

Manufacturer: <\/b>Virbac Animal Health, Inc. (Fort Worth, Texas)<\/span><\/p>\n

Mechanism of action: <\/b>Tigilanol tiglate<\/a> is a novel diterpene ester that is a potent cellular signaling molecule. Anti-tumor effectiveness of tigilanol tiglate <\/b>is believed to be due to 3 key mechanisms: direct oncolysis of tumor cells via disruption of mitochondrial function; protein kinase C activation resulting in an acute inflammatory response throughout the tumor that causes localized hypoxia and recruits innate immune cells; and destruction of tumor vasculature.9,10<\/sup><\/span><\/p>\n

Indication: <\/b>Stelfonta is labeled for the treatment of nonmetastatic cutaneous (located anywhere on the body) or subcutaneous (located at or distal to the elbow or hock) mast cell tumors (MCTs) in dogs. Treated MCTs should be less than 10 cm3<\/sup> in size (see label for calculation formula).9,10<\/sup><\/span><\/p>\n

Handling: <\/b>Personal protective equipment (disposable gloves, protective eyewear, and a lab coat or gown) should be worn when handling Stelfonta. Caution is recommended during treatment to avoid accidental self-injection.9<\/sup><\/span><\/p>\n

Administration: <\/b>Stelfonta is administered as an intratumoral injection via a 23-gauge needle and a single injection site, using a fanning motion to disperse the drug throughout the tumor. Tumor volume measurements and dosing calculations should be followed closely as outlined in the package insert. Consider sedating dogs for administration and post-treatment pain management medications as clinically indicated. Concomitant medications (prednisone\/prednisolone, diphenhydramine, famotidine) must be administered as outlined due to potential for systemic effects of mast cell degranulation.9,10<\/sup><\/span><\/p>\n

Key clinical data:<\/b> In the pivotal trial that enrolled 123\u00a0dogs with MCTs, 81 were treated with Stelfonta while 42 were in the untreated control group. Single treatment with Stelfonta resulted in 75% complete response by 28 days compared with 5.3% in the control group. No recurrence was noted in 93% of responding Stelfonta-treated dogs at 84 days post-treatment. Most wounds were healed by 28 to 42 days post-treatment. Wounds only rarely required bandaging or antibiotics.9,10<\/sup> A separate publication that evaluated response at 12 months after Stelfonta treatment indicated that 89% remained tumor free at the treatment site; 11% had developed recurrence within the first 6 months after treatment.11<\/sup><\/span><\/p>\n

Most common side effects: <\/b>The most commonly noted adverse effects (wound formation, injection site pain, lameness in treated limb, injection site bruising\/erythema\/edema) are directly related to the mechanism of action of the drug. Other common side effects included vomiting, diarrhea, hypoalbuminemia, and anorexia. Most side effects were low grade and transient.9,10<\/sup><\/span><\/p>\n

Clinical use: <\/b>Stelfonta should be considered as a local treatment option for nonmetastatic MCTs (<10 cm3<\/sup>) in dogs. This is especially appealing when surgery may not be a good option based on tumor location, patient status, or client considerations. Client education and setting appropriate expectations regarding wound formation and management are important for case management success. As histologic grade is not available for MCTs treated with Stelfonta (unless incisional biopsy is performed and the site allowed to heal for 14 days prior), utilizing other prognostic indicators is important. Obtaining a cytologic grade of the MCT and aspirating the regional lymph node (if possible) should be considered.\u00a0<\/span><\/span><\/p>\n

Palladia (toceranib phosphate tablets)<\/h3>\n

Approval status: <\/b>FDA approved (2009)<\/span><\/p>\n

Manufacturer: <\/b>Zoetis Inc. (Kalamazoo, Michigan)<\/span><\/p>\n

Mechanism of action: <\/b>Receptor tyrosine kinases (RTKs) are a family of highly regulated cell signaling proteins that play a key role in normal cell growth and differentiation. Dysregulation of RTKs, resulting in continual signal activation, has been identified in several types of cancer in human and veterinary medicine. Members of the RTK family also play key roles in angiogenesis (new blood vessel development), an important process for tumor growth, survival, and metastasis. By inhibiting several members of the split-kinase family of RTKs, including vascular endothelial growth factor receptor-2 (VEGFR-2), platelet-derived growth factor receptor-<\/span>\u03b2<\/span> (PDGFR-<\/span>\u03b2<\/span>), and Kit\/stem cell factor receptor (SCFR), toceranib has an antiangiogenic as well as a direct antitumor role in treating canine MCTs12,13<\/sup> and, potentially, other types of cancer.<\/span><\/p>\n

Indication: <\/b>Palladia is labeled for the treatment of dogs with recurrent cutaneous Patnaik grade II or III MCT.12<\/sup> Evidence of biologic activity has been reported in several other types of cancer in dogs (<\/span>BOX 1<\/span><\/strong>). Use of Palladia outside of the above indication is off-label use, and appropriate clarification and client education should be provided in these cases.<\/span><\/p>\n

BOX 1 Canine Cancers That May Benefit From Palladia Therapy<\/div>
<\/p>\n