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.

Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours.

The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®, Pfizer Animal Health, Madison, NJ, USA) in select solid tumours in dogs. Cases in which toceranib was used to treat dogs with apocrine gland anal sac adenocarcinoma (AGASACA), metastatic osteosarcoma (OSA), thyroid carcinoma, head and neck carcinoma and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 AGASACA [8 partial response (PR), 20 stable disease (SD)], 11/23 OSAs (1 PR and 10 SD), 12/15 thyroid carcinomas (4 PR and 8 SD), 7/8 head and neck carcinomas [1 complete response (CR), 5 PR and 1 SD] and 5/7 (1 CR and 4 SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg kg(-1) , 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis and 47/63 (74.6%) were treated 4 months or longer. Although these data provide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumours, future prospective studies are necessary to define its true activity.

Efficacy and toxicity of BOPP and LOPP chemotherapy for the treatment of relapsed canine lymphoma.

Mechlorethamine (Mustargen), Oncovin) (vincristine), procarbazine and prednisone (MOPP) chemotherapy is useful for relapsed canine lymphoma. This study evaluates the efficacy of MOPP after substitution of CCNU (lomustine, LOPP protocol) or BCNU (carmustine, BOPP protocol) for mechlorethamine in 60 dogs with relapsed lymphoma. Seven of 14 (50%) dogs treated with BOPP responded, for a median of 129.5 days for complete responders (range 9-354 days) and a median of 140 days for partial responders (range 4-276 days). Twenty-three of 44 (52%) dogs treated with LOPP responded for a median of 112 days for complete responders (range 48-250 days) and a median of 84.5 days for partial responders (range 69-290 days). Two dogs receiving a combination of LOPP and BOPP partially responded for 28 and 163 days, respectively. With BOPP chemotherapy, nine dogs (20.5%) and seven dogs (50%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seven dogs (50%) had one or more episodes of Grade II or higher gastrointestinal toxicity. While receiving LOPP chemotherapy, 28 dogs (63.6%) and 17 dogs (38.6%) had one or more episodes of Grade II or higher neutropenia and thrombocytopenia, respectively. Seventeen dogs (38.6%) had one or more episodes of Grade II or higher gastrointestinal toxicity. Overall, there were 17 non-fatal treatment-related episodes of sepsis requiring hospitalization. Eight dogs (13%) died or were euthanized because of treatment-related sepsis and/or chemotherapy-related complications. Severe haematologic toxicity, coupled with the improved response duration observed in dogs receiving reduced doses during B/L-OPP rescue, underscores the need for protocol optimization.

Curative-intent radiation therapy as a treatment modality for appendicular and axial osteosarcoma: a preliminary retrospective evaluation of 14 dogs with the disease.

Canine osteosarcoma is a common bone malignancy associated with aggressive local disease and rapid metastasis. Current local therapeutic modalities do not provide curative-intent options for dogs with significant orthopaedic or neurologic disease, dogs which are denied amputation or dogs with non-resectable lesions. The goals of this retrospective study included the evaluation of local control, survival, and time to the development of metastases in 14 dogs treated with curative-intent radiation therapy and chemotherapy. Median local disease control was 202 days (79-777). Median survival was 209 days (79-781). Median time to metastasis was 314 days (7-645). No significant correlation was found between the outcome and pre-treatment alkaline phosphatase levels, radiographic appearance, tumour site, radiation dose or chemotherapeutics administered. In these dogs, full-course radiation therapy in conjunction with chemotherapy was not found to yield equivalent results to the standard of care options.

Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs.

Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.

Factors influencing survival after radiotherapy of nasal tumors in 130 dogs.

Improvements in survival of dogs with nasal tumors have been slow to develop throughout the past three decades. Despite multiple studies examining various radiation time-dose schema, the advancement of CT-based computerized treatment planning, and the evaluation of detailed staging systems, the optimal treatment regimen, and most important prognostic factors regarding survival remain unclear. In this study, data from four previous studies were combined with data from 44 additional dogs, and this population of 130 dogs was evaluated for factors which influenced survival. Twenty-one dogs were treated with orthovoltage at the University of Pennsylvania. One hundred nine dogs were treated with cobalt photons at North Carolina State University. Sixty-five of these 109 dogs had been previously described. Of the 44 dogs not previously described, 35 were treated with a shrinking field technique. Survival was determined from the medical record, or from information derived by telephone or mail survey. The univariate Cox regression model was used to examine for relationship between various patient, tumor, and treatment variables and survival. Significant relationships identified in the univariate analysis were further analyzed using the multivariate Cox regression model. Median survival of the 130 dogs was 8.9 months (95% C.I., 8-11 months). In the univariate analysis, the following variables were associated with decreased survival: 1) age >10 years old, 2) regional lymph node metastasis, 3) advanced tumor stage, 4) use of megavoltage radiation, 5) overall total dose >55 Gray, and 6) boost technique performed. In a multivariate analysis of 125 dogs with complete data for age, radiation type, and radiation dose, age (p < .001) and radiation type (p = .02) were identified as joint predictors of survival. After adjusting for age, the staging system lost prognostic significance (p = .06). In a subset of dogs that received cobalt radiation, after adjusting for age, dogs treated with a boost technique had decreased survival (p = .001). In general, local control of canine nasal tumors following aggressive radiation therapy is poor. Early diagnosis and selection of appropriate patients is warranted and palliative types of treatment should be considered in dogs with a poor chance of long term survival.

Palliative radiotherapy of appendicular osteosarcoma in 95 dogs.

Ninety-five dogs with either a presumptive (n = 24) or biopsy confirmed diagnosis (n = 71) of osteosarcoma received palliative radiotherapy using 60Co photons. Parallel opposed beams were used with each dog receiving either 10 Gy on days 0, 7 and 21 (n = 58) or 8 Gy on days 0 and 7 (n = 37). The 8 Gy fractionation scheme was given with the intent of retreating upon relapse from pain relief. Only 9 of 37 (24%) dogs in the 8 Gy group returned for retreatment. Forty-seven of the 95 dogs (49%) received concurrent or sequential chemotherapy. Seventy of the 95 dogs (74%) experienced pain relief following treatment. In dogs experiencing pain relief the median duration of response was 73 days. Numerous clinical variables were evaluated as predictors of response. The only variable significantly related to achieving a response was the use of chemotherapy. The following variables were significantly related to the duration of response: extent of bone lysis, chemotherapy use, length of bone involved and tumor site (humerus). In a multivariate analysis (n = 73 dogs), after adjusting for chemotherapy use, extent of bone involvement (p = 0.01) and tumor site (p = 0.02) retained statistical significance, while degree of bone lysis did not (p = 0.11). No difference in response incidence or duration was found between 3 fractions of 10 Gy vs. 2 fractions of 8 Gy. Administration of a low initial dose with the intent of retreatment was not a successful strategy.

Radiation therapy for incompletely resected canine mast cell tumors.

The records of 56 dogs treated with megavoltage radiation for mast cell neoplasia were reviewed to determine the efficacy of this treatment modality. Total radiation dose ranged from 45 to 57 Gray (Gy), dose per fraction ranged from 3.0 to 4.0 Gy, and radiation treatment time ranged from 14-28 days. Median disease free interval (95% CI) was 32.7 (19-70) months. Median disease free interval for dogs older than 7.5 years was 15 (lower limit 7) months as compared to 62 (lower limit 20) for dogs younger than 7.5 years of age (p = 0.006). Median disease free interval for dogs with measurable disease was 12 (lower limit 5) months as compared to 54 (32-70) months for dogs with microscopic disease (p = 0.006). Radiation treatment time was also significantly related to disease free interval. Median disease free interval for dogs treated longer than 22 days was 12 (7-19) months as compared to greater than 50 (lower limit 20) months for dogs treated in 22 or fewer days (p < 0.001). This appeared to be due to more recurrences in dogs treated with 3-per-week fractionation and suggests that tumor proliferation in the interfraction interval may be important. Sex, tumor location, histologic grade, WHO clinical stage, number of radiation fractions, total radiation dose, and dose-per-fraction, as well as the following "yes/no" variables: steroids given, surgery prior to radiation, lymph nodes irradiated, and development of another mast cell tumor did not appear to influence median disease free interval or survival. Data presented herein support megavoltage radiation as an effective treatment for canine mast cell neoplasia, and suggest that disease free interval in dogs treated with daily fractions may be longer than that achieved with alternating day fractions.

Spectrophotometric ribonuclease assays using dinucleoside monophosphate substrates.

A pair of ribonuclease assays have been developed which offer improvements in specificity, simplicity, and/or sensitivity over current procedures. The assays measure the rate of adenosine release upon ribonuclease hydrolysis of 3'-adenosyl dinucleoside monophosphate substrates. Adenosine formation is spectrophotometrically determined by combining a coupled-enzyme system (adenosine deaminase or an adenosine deaminase/nucleoside phosphorylase/xanthine oxidase combination) to the ribonuclease cleavage. As demonstrated by a brief characterization of the ribonuclease activities in several mouse tissues, the methods demonstrate the advantage of being able to discriminate between ribonucleases of differing substrate specificities. An interesting guanosyl(3'-5')adenosine-specific ribonuclease in mouse brain has been identified using these assay methods.