Efficacy of dacarbazine as a rescue agent for histiocytic sarcoma in dogs.

BACKGROUND: Canine histiocytic sarcoma (HS) is an aggressive neoplasm that is generally associated with a poor prognosis. CCNU is considered first-line medical therapy, although the majority of dogs ultimately develop progressive disease. The objective of this study was to evaluate the efficacy of dacarbazine as a rescue agent for HS. MATERIALS AND METHODS: Medical records of dogs diagnosed with HS that received at least one dose of dacarbazine were reviewed. Information collected and analyzed included signalment, disease distribution, treatment history, dacarbazine treatments (including dose, interval and total number of cycles), adverse events, and response to treatment. RESULTS: Seventeen dogs were included, all of which had disseminated or metastatic disease and had received prior treatment with CCNU. Three dogs achieved partial remission for an overall response rate of 17.6%. The overall median event-free survival (EFS) was 21 days. For dogs that experienced an objective response, the EFS was 70 days. Toxicity secondary to dacarbazine was generally mild and self-limiting. CONCLUSION: In the setting of advanced disease, dacarbazine appears to have modest activity against HS and warrants further investigation.

Extravasation reactions associated with the administration of pamidronate: 11 cases (2008-2013).

Pamidronate is a bisphosphonate drug widely utilized in veterinary oncologic practice for the palliation of malignant osteolysis. Pamidronate has not been previously reported to cause tissue injury upon extravasation in dogs. The medical records of 11 client-owned dogs undergoing palliative treatment for primary bone tumors with known or suspected pamidronate extravasation reactions were reviewed. The majority of adverse events were low grade in nature, however in some cases, the reactions were severe and led to euthanasia in one instance. Time to complete resolution of lesions ranged from within several days to greater than one and a half months. Aside from the dog that was euthanized, no long-term sequelae of extravasation were identified. Treatments employed to address the reactions varied widely. Pamidronate extravasation reaction appears to be an uncommon, but potentially serious complication of intravenous administration.

Criteria for designation of clinical substage in canine lymphoma: a survey of veterinary oncologists.

Clinical substage is frequently reported to be prognostic in dogs with lymphoma, yet formal criteria for defining this parameter are lacking. The World Health Organization TNM Classification of Tumors of Domestic Animals simply defines substage as the absence or presence of systemic signs (substages a and b, respectively). We designed a survey to query veterinary oncologists on the criteria they use to determine clinical substage in practice. Gastrointestinal, constitutional and respiratory signs were the most commonly identified clinical factors, with greater than 90% respondents indicating that inappetence, vomiting, diarrhoea, changes in attitude, weakness and dyspnea were integral in assigning clinical substage. Nevertheless, more than three-quarters of respondents also considered metabolic, neurologic and nutritional parameters when making this determination. For most factors, respondents reported mild-to-moderate severity of clinical signs was sufficient for substage b designation.

Association between Body Condition Score and Cancer Prognosis in Dogs with Lymphoma and Osteosarcoma.

BACKGROUND: In humans and rodents obesity appears to promote some cancers by increasing incidence, tumor aggressiveness, recurrence, and fatality. However, the relationship between obesity and cancer in dogs has not been thoroughly evaluated. HYPOTHESIS/OBJECTIVES: Whether body condition score (BCS) at the time of lymphoma (LSA) or osteosarcoma (OSA) diagnosis in dogs is predictive of survival time (ST) or progression-free interval (PFI). We hypothesized that an overweight body state at the time of cancer diagnosis would be associated with negative outcomes. ANIMALS: Dogs with LSA (n = 270) and OSA (n = 54) diagnosed and treated between 2000 and 2010. METHODS: Retrospective case review. Signalment, body weight, BCS, cancer diagnosis and treatment, relevant clinicopathologic values, and survival data were collected. Dogs were grouped by BCS (underweight, ideal, and overweight) and ST and PFI were compared. RESULTS: Overall, 5.5% of dogs were underweight, 54.0% were ideal weight, and 40.4% were overweight at diagnosis. Underweight dogs with LSA had shorter ST (P = .017) than ideal or overweight dogs. BCS was not associated with ST for OSA (P = .474). Progression-free interval did not differ among BCS categories for either cancer. CONCLUSIONS AND CLINICAL IMPORTANCE: Obesity was not associated with adverse outcomes among dogs with LSA or OSA in this retrospective study; however, being underweight at the time of diagnosis of LSA was associated with shorter survival. More research is needed to elucidate the relationship between excessive body weight and cancer development and progression in dogs.

Efficacy of maropitant in the prevention of delayed vomiting associated with administration of doxorubicin to dogs.

BACKGROUND: Vomiting, nausea, inappetence, and diarrhea are common delayed adverse effects of doxorubicin. Maropitant, a neurokinin-1 receptor antagonist, is known to prevent acute vomiting in dogs receiving cisplatin. OBJECTIVE: To evaluate the efficacy of maropitant in preventing delayed vomiting after administration of doxorubicin to dogs. ANIMALS: Fifty-nine dogs with cancer. METHODS: This randomized, double-blind, placebo-controlled study used a cross-over design. Dogs were randomized into 1 of 2 treatment groups. Group A received maropitant after the 1st doxorubicin, and placebo after the 2nd. Group B received placebo first, and maropitant second. Maropitant (2 mg/kg) or placebo tablets were administered PO for 5 days after doxorubicin treatment. Owners completed visual analog scales based on Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events to grade their pet's clinical signs during the week after administration of doxorubicin. Statistical differences in gastrointestinal toxicosis and myelosuppression between maropitant and placebo treatments were evaluated. RESULTS: Significantly fewer dogs had vomiting (P=.001) or diarrhea (P=.041), and the severity of vomiting (P<.001) and diarrhea (P=.024) was less the week after doxorubicin when receiving maropitant compared with placebo. No differences were found between maropitant and placebo for other gastrointestinal and bone marrow toxicoses. CONCLUSIONS AND CLINICAL IMPORTANCE: Maropitant is effective in preventing delayed vomiting induced by doxorubicin. Its prophylactic use might improve quality of life and decrease the need for dose reductions in certain dogs.

Dacarbazine as single-agent therapy for relapsed lymphoma in dogs.

BACKGROUND: Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma. HYPOTHESIS: Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy. ANIMALS: Forty client-owned dogs with relapsed lymphoma. METHODS: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800-1,000 mg/m(2) every 2-3 weeks as a 4-5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed. RESULTS: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7-14 days after the treatment. Treatments were delayed because of thrombocytopenia. CONCLUSIONS: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.

Antioxidant status and biomarkers of oxidative stress in dogs with lymphoma.

BACKGROUND: Oxidative stress might play a role in carcinogenesis, as well as impacting morbidity and mortality of veterinary cancer patients. The purpose of this study was to evaluate antioxidant concentrations and biomarkers of oxidative stress in dogs with newly diagnosed lymphoma before treatment and once in remission, with comparison with healthy controls. HYPOTHESIS: Dogs with lymphoma have increased oxidant and reduced antioxidant concentrations compared with healthy controls, and that these abnormalities normalize once remission is achieved. ANIMALS: Seventeen dogs with lymphoma and 10 healthy controls. METHODS: Prospective, observational study. Measures of oxidative stress [malondialdehyde and total isoprostanes (isoP)] and antioxidants [alpha-tocopherol, gamma-tocopherol, oxygen radical absorbance capacity (ORAC), and glutathione peroxidase (GSHPx)] were assessed in dogs with newly diagnosed lymphoma before treatment compared with healthy control dogs. The same parameters were measured in the dogs with lymphoma on week 7 of the chemotherapy protocol when all dogs were in remission. RESULTS: At baseline, dogs with lymphoma had significantly lower alpha-tocopherol (P <.001) and gamma-tocopherol (P= .003) but higher GSHPx (P= .05), ORAC (P= .001), and isoP (P < .001) compared with healthy controls. In the dogs with lymphoma, alpha-tocopherol concentrations were higher (P= .005) and ascorbic acid were lower (P= .04) after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Results suggest that dogs with lymphoma have alterations in oxidant and antioxidant concentrations and that the status of some of these biomarkers normalize after remission. Further studies are warranted to determine whether antioxidant interventions to correct these are beneficial in the treatment of canine lymphoma.

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.

Mushroom-derived maitake PETfraction as single agent for the treatment of lymphoma in dogs.

BACKGROUND: Maitake PETfraction is a standardized essence extracted from the mushroom Maitake (Grifola frondosa) that has antitumor activity in tumor-bearing mice. In addition, PETfraction induces apoptosis in human prostate and bladder cancer cells and suppresses the proliferation in vitro of several canine tumor cell lines, such as lymphoma (Cl-1), mammary gland (CF33), and connective tissue (CF21). HYPOTHESIS: Maitake PETfraction is effective as a single agent in dogs with lymphoma. ANIMALS: Fifteen dogs with confirmed intermediate or high-grade lymphoma were enrolled into this prospective, noncontrolled, clinical trial. Inclusion criteria were an expected survival time of at least 2 weeks and no major organ dysfunction. METHODS: Maitake PETfraction was administered at a dose of 3 drops/kg/day divided into 2 doses given 1 hour before feeding. Dogs were evaluated by physical examination with tumor measurement, body weight, CBC, and chemistry profile before treatment and after 2, 4, 8, and 12 weeks. At each visit, owners completed a questionnaire addressing overall quality of life, appetite, and any adverse effects noted. RESULTS: A decrease in lymph node size of greater than 50% (objective response) was not seen in any of the dogs. Thirteen dogs developed progressive disease before the 4th week. The median treatment duration was 27 days (range, 9-228). PETfraction was well accepted, and minimal adverse effects were observed. Two dogs developed hyphema. It was not known if this was related to progressive lymphoma or was an adverse effect of treatment. CONCLUSIONS: No objective responses were observed to administration of Maitake PETfraction, and the drug was well tolerated in these dogs.

Combined doxorubicin and cyclophosphamide chemotherapy for nonresectable feline fibrosarcoma.

A retrospective evaluation was performed on 12 cats with nonresectable, histopathologically confirmed fibrosarcomas that were treated with doxorubicin and cyclophosphamide chemotherapy. All of the tumors were located in sites potentially used for vaccination. Six cats had a greater than 50% decrease in gross tumor burden. However, the responses were not durable, with a median response duration of 125 days. All cats developed progressive disease. When animals that received other treatments after doxorubicin-based chemotherapy were eliminated from the analysis, median survival time was significantly longer for cats that responded to chemotherapy compared with the median survival time for nonresponders (242 and 83 days, respectively). These findings may serve as a basis for further evaluating the role of chemotherapy in the treatment of vaccine-associated sarcomas.

Neuro-ophthalmologic findings in the Asperger disorder.

Asperger disorder is a complex behavioral disorder that may be related to autism. We examined a 49-year-old man with Asperger disorder who had multiple neuro-ophthalmologic abnormalities, including colobomatous defects involving the optic discs and peripapillary retina, and abnormal ocular motility with an oculocephalic dyskinesia. Asperger disorder may be associated with a variety of neuro-ophthalmologic disturbances.