**4. Treatment of CTVT**

CTVT cells respond to many forms of therapy. Historically, CTVT has been treated with surgical excision therapy and followed by several chemotherapeutic cocktails or a combination of chemotherapeutic protocols or radiotherapy. Surgery is chosen for a localized CTVT mass, but it is not recommended in generalized or metastatic cases. Electrosurgery and cryosurgery are optional surgical methods because the tumor is easily transplanted to surgical wounds when using the conventional surgical method. The rate of recurrence after conventional surgery was between 12 and 68% [13]. Surgical methods have a higher recurrence rate than chemotherapy. Radiotherapy was chosen as the therapy for CTVT cases with complete regression within 1–3 treatments of a dose of 10 Gy or 1000 rad. Although radiotherapy is a successful treatment, this method requires sedation for dogs, specialized technicians, and expensive equipment [13].

The original combining protocol was composed of vincristine, cyclophosphamide, and methotrexate. Also, there have been attempted combination protocols, such as cyclophosphamide and prednisolone, vinblastine with cyclophosphamide, vinblastine with methotrexate, and vincristine with ivermectin [13]. After clinical evaluation and development of chemotherapy for CTVT treatment, the use of vincristine, vinblastine, and doxorubicin, as single agents were attempted. The duration of vincristine for complete remission is around 4–6 weeks of intravenous administration at a weekly dose of 0.025 mg/kg bodyweight [11, 32]. CTVT cases are treated using vinblastine intravenously in a dose of 0.1 mg/kg bodyweight on four to six weekly treatments [13]. Moreover, complete remission was also reported within three weeks in the doxorubicin treatment when given intravenously at a weekly dose of 30 mg/m<sup>2</sup> surface area [19, 32]. Vincristine has been reported as the most effective, safe, and convenient agent for GTVT and ETVT cases. The better response to vincristine treatment may be due to less myelosuppression compared to doxorubicin and no immunosuppression by methotrexate. However, weight loss, mild leukopenia, and gastrointestinal toxicity, such as anorexia, nausea, and vomiting, are common adverse effects of vincristine treatment in less than 10% of cases. An additional complication of vincristine treatment is the extravasation of the drug during administration causing necrotic ulcer lesions of the affected skin [19].

Recently, the combination of vincristine (VCR) and L-asparaginase (LAP) protocol or VCR-LAP protocol has demonstrated an effective treatment result and shorter treatment time than VCR alone. The VCR-LAP combination protocol is given

### *Canine Transmissible Venereal Tumor: An Infectious Neoplasia in Dogs DOI: http://dx.doi.org/10.5772/intechopen.106150*

in alternating weekly doses of 5000 IU/m<sup>2</sup> of LAP subcutaneously and 0.025 mg/kg of VCR intravenously. The duration of combination protocols is 2–5 weeks, with no evidence of VCR-resistant cases. The short period of treatment provides fewer opportunities for chemotherapeutic drug resistance. Moreover, the combined protocol costs less on average than mono-chemotherapy [11]. A comparative treatment study via a murine model of vascular targeted photodynamic therapy was performed as the new strategy for chemotherapeutic-resistant cases [33]. Moreover, VCR-resistant status is still increasing, not only in ETVT cases but also in GTVT cases [11, 32, 34]. When only partial remission was noted in seven and eight weeks, a 30 mg/m<sup>2</sup> dose of doxorubicin was administered as mono-chemotherapy every three weeks for a total of five treatments [19]. The duration of doxorubicin treatment was around three applications or two months. In addition, four treatments of vincristine 0.025 mg/kg bodyweight with LAP 10,000 IU/m<sup>2</sup> every two weeks were also used in resistance cases that showed complete regression [34].

The best thing for veterinarians to keep in mind is that this contagious cancer can be treated with chemotherapy and achieve complete regression. Also, the mono-chemotherapeutic drug VCR can cure this cancer and is recommended as the chemotherapeutic drug of choice for CTVT treatment. Recovery rates are high in more than 90% of cases and have been documented by using VCR at a 0.025 mg/kg body weight dosage over two to eight weeks. The mixed and plasmacytic cytomorphologic types show malignant behavior related to vincristineresistant and recurrent cases [26]. However, the lymphocytic type has been shown to be less malignant than other types. The larger cell size or the increase in the cellular and nuclear size of tumor cells may demonstrate the survival ability of cells and the progression of tumor grading [35, 36]. Also, the lymphocytic type was found in GTVT cases and was not related to metastasis behavior [26]. According to the anatomical lesion, this can infer that GTVT has a lower malignant behavior than ETVT [11, 26]. In VCR treatment cases, the lymphocytic type had the shortest time to complete regression. The prognosis of treatment with VCR is influenced by the stage of growth, the cytomorphologic type, the size of the tumor, the anatomical site of the mass, and the climate [13, 26, 32]. Recurrence of CTVT was rare because of the effectiveness of chemotherapy. However, some recurrent cases were reported six months after complete remission. So, long-term monitoring after cessation of treatment should be more than six months (**Figure 3**) [11, 32].

**Figure 3.** *The lesion at the penis before (3A) and after complete remission (3B).*
