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.

The purpose of this study was to evaluate the efficacy and toxicity of a single-agent, dose-intensified doxorubicin protocol in canine hemangiosarcoma (HSA). Canine HSA is a highly malignant tumor, and most affected dogs die within 6 months of diagnosis. Doxorubicin is the most, and possibly the only, effective chemotherapeutic drug for this malignancy, but it provides only moderate improvement in survival. On the basis of previous studies reporting similar survival in dogs treated with doxorubicin as a single agent and doxorubicin-based combination chemotherapy and the concept of summation dose intensity, a dose-intensified single-agent doxorubicin protocol was initiated. Twenty dogs with HSA were recruited to participate in this study. Workup and staging were performed according to standard practice. Chemotherapy was initiated within 3 weeks of surgery. Doxorubicin was scheduled to be administered at 30 mg/m2 i.v. every 2 weeks for a total of 5 treatments. The dogs were monitored for toxicity and signs of recurrence during and at regular intervals after chemotherapy. The protocol was tolerated well. No dogs were hospitalized because of adverse effects or developed clinical signs consistent with doxorubicin-induced cardiomyopathy. There was a significant difference in survival in dogs with stage I and I1 HSA compared with dogs with stage III HSA. with median survival times of 257, 210, and 107 days, respectively. These results are slightly better than the historical control with respect to toxicity and efficacy but are not statistically different from what is achieved with standard treatments. There was no association between dose intensity and outcome.

The etiopathogenesis of feline mammary carcinoma is not well understood. Although putative, risk factors include breed, reproductive status, and regular exposure to progestins. An association between age at ovarihysterectomy (OHE) and mammary carci-noma development has not been established. Therefore, a case-control study was performed to determine the effects of OHE age, breed, progestin exposure, and parity on feline mammary carcinoma development. Cases were female cats diagnosed with mammary carcinoma by histological examination of mammary tissue. Controls were female cats not diagnosed with mammary tumors selected from the same biopsy service population. Controls were frequency matched to cases by age and year of diagnosis. Questionnaires were sent to veterinarians for 308 cases and 400 controls. The overall questionnaire response rate was 58%. Intact cats were significantly overrepresented (odds ratio [OR] 2.7, confidence interval [CI] 1.4-5.3, P .001) in the mammary carcinoma population. Cats spayed prior to 6 months of age had a 91% reduction in the risk of mammary carcinoma development compared with intact cats (OR 0.9, CI 0.03-0.24). Those spayed prior to 1 year had an 86% reduction in risk (OR 0.14, CI 0.06-0.34). Parity did not affect feline mammary carcinoma development, and too few cats had progestin exposure to determine association with mammary carcinoma. Results indicate that cats spayed before 1 year of age are at significantly decreased risk of feline mammary carcinoma development.

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 1 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 1 Chemo group. No differences in clinical data were found between Sx and Sx 1 Chemo groups. Median DFS times for the Sx and Sx 1 Chemo groups were 372 and 676 days, respectively (P 5 .15) and median survival times (ST) were 1,406 and 848 days, respectively (P 5 .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx 1 Chemo compared with the Sx group (1,998 versus 414 days, respectively; P 5 .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.

Cell-based active immunotherapy for cancer is a promising novel strategy, with the first dendritic cell (DC) vaccine achieving regulatory approval for clinical use last year. Manufacturing remains arduous, especially for DC vaccines, and the prospect of using cell-based immunotherapy in the adjuvant setting or in combination with chemotherapy remains largely untested. Here, we used a comparative oncology approach to test the safety and potential efficacy of tumor RNA-loaded, CD40-activated B cells in privately owned dogs presenting with non-Hodgkin's lymphoma (NHL), a clinical scenario that represents not only a major problem in veterinary medicine but also a bona fide spontaneous animal model for the human condition. When administered to NHL dogs in remission after induction chemotherapy, CD40-B cells electroporated ex vivo with autologous tumor RNA safely stimulated immunity in vivo. Although chemotherapy plus CD40-B vaccination did not improve time-to-progression or lymphoma-specific survival compared to dogs treated with chemotherapy alone, vaccination potentiated the effects of salvage therapy and improved the rate of durable second remissions as well as subsequent lymphoma-specific survival following salvage therapy. Several of these relapsed dogs are now long-term survivors and free of disease for more than a year. Overall, these clinical and immunological results suggest that cell-based CD40 cancer vaccination is safe and synergizes with chemotherapy to improve clinical outcome in canine NHL. More broadly, our findings underscore the unique value of clinical investigations in tumor-bearing companion animals.