Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline mammary carcinoma.

BACKGROUND: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. HYPOTHESIS: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. ANIMALS: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). METHODS: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. RESULTS: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.

RNA-loaded CD40-activated B cells stimulate antigen-specific T-cell responses in dogs with spontaneous lymphoma.

Cell-based vaccination strategies to induce functional tumor-specific T cells in cancer patients have focused on using autologous dendritic cells. An alternative approach is to use RNA-loaded CD40 activated B cells (CD40-B) that are highly efficient antigen-presenting cells capable of priming naive T cells, boosting memory T-cell responses and breaking tolerance to tumor antigens. The use of tumor RNA as the antigenic payload allows for gene transfer without viruses or vectors and permits major histocompatibility complex (MHC)-independent, multiple-antigen targeting. Here, we use CD40L transfected K562 cells to generate functional CD40-B cells from the peripheral blood of humans and dogs. Testing of RNA-loaded CD40-B cells in dogs allows not only for its development in veterinary medicine but also for determination of its safety and efficacy in a large animal model of spontaneous cancer prior to initiation of human clinical trials. We found that CD40-B cells from healthy humans, healthy dogs and tumor-bearing dogs express increased levels of immune molecules such as MHC and CCR7. Moreover, RNA-loaded CD40-B cells induce functional, antigen-specific T cells from healthy dogs and dogs with lymphoma. These findings pave the way for immunotherapy trials using tumor RNA-loaded CD40-B cells to stimulate antitumor immunity in a large animal model of spontaneous neoplasia.

Characterization of the biological behaviour of appendicular osteosarcoma in Rottweilers and a comparison with other breeds: a review of 258 dogs.

The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fifty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no significant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confirm that these differences were associated with a worse outcome.