Intratumoral recombinant human interferon alpha‐2a and vincristine combination therapy in canine transmissible venereal tumour

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Abstract

Canine transmissible venereal tumour (CTVT) is a naturally occurring contagious neoplasm of dogs located mainly on the external genitalia of both sexes. The course of vincristine chemotherapy, the most effective and practical therapy, is affected by the immune status of the host. The aim was to investigate recombinant human interferon alpha-2a (rhIFNα-2a) and vincristine for treatment of CTVT. A total of 21 female dogs were included. In group I (n = 9), vincristine (0.025 mg/kg, IV) was administered weekly. In group II (n = 6), dogs were injected intratumorally weekly with 1.5 million IU rhIFNα-2a. In group III (n = 6), rhIFNα-2a and vincristine were combined. No tumour regression was observed after three injections of rhIFNα-2a in group II and weekly vincristine was administered. The number of tumour infiltrating lymphocytes (TILs), mitotic figures and apoptotic cells were counted in subsequent incisional tumour biopsies. The Kaplan-Meier Method was used to analyse survival using complete tumour regression as the outcome and Breslow Test was used for comparison of survival curves. Differences in TILs, cell proliferation and apoptosis between groups were assessed by analysis of covariance. Complete regression was observed in all animals included. Mean duration of vincristine treatment for complete regression was shorter in group II (3.50 weeks, 95% CI, 3.06-3.94, P < 0.05) and group III (3.17 weeks, 95% CI, 2.84-3.49, P < 0.01) compared to group I (5.11 weeks, 95% CI, 4.42-5.80). Vincristine and rhIFNα-2a combination increased TILs in CTVT biopsies compared to vincristine treatment (P = 0.017) and vincristine treatment after rhIFNα-2a (P = 0.049). Vincristine treatment after rhIFNα-2a (Group II; P < 0.001) and rhIFNα-2a and vincristine combination (Group III; P < 0.001) decreased apoptosis. The results indicate that intratumoral rhIFNα-2a treatment alone is not effective in CTVT. However, combination of rhIFNα-2a and vincristine shortens the duration of treatment compared to vincristine therapy.

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