Browsing by Author "Kitchell, Barbara E."
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- Clinicopathologic Significance of Histologic Grade, Pgp, and P53 Expression in Canine LymphomaDhaliwal, Ravinder S.; Kitchell, Barbara E.; Ehrhart, E. J.; Valli, Victor E.; Dervisis, Nikolaos G. (American Animal Hospital Association, 2013-05-01)To characterize the expression of P-glycoprotein (Pgp) and p53 in different histologic grades of canine multicentric lymphosarcoma (LSA), 31 cases of LSA without prior treatment were studied. The expression levels of the Pgp and p53 proteins were evaluated for their clinicopathologic significance among standard histologic evaluation. Immunohistochemistry (IHC) was performed on formalin-fixed, paraffin-embedded archival samples of 31 previously untreated LSA cases to detect the expression of Pgp and p53. All dogs were subsequently treated with a combination chemotherapy protocol. Remission and survival durations were evaluated for correlation with histologic grade and presence of drug resistance markers. Of the 31 cases, 24 (80%) and 7 (22%) were positive for Pgp and p53, respectively. Overall, the median survival and duration of remission in the study was 246 days and 137 days, respectively. The National Cancer Institute working formulation histologic grade was not associated with either survival or duration of first remission (DOR). The Pgp protein expression and DOR and survival was not statistically significant. Expression of p53 was statistically correlated with survival.
- Efficacy of temozolomide or dacarbazine in combination with an anthracycline for rescue chemotherapy in dogs with lymphomaDervisis, Nikolaos G.; Dominguez, Pedro A.; Sarbu, Luminita; Newman, Rebecca G.; Cadile, Casey D.; Swanson, Christine N.; Kitchell, Barbara E. (American Veterinary Medical Association, 2007-08-15)Objective: To compare results of treatment with temozolomide or dacarbazine, in combination with an anthracycline, in dogs with relapsed or refractory lymphoma. Design: Nonrandomized, controlled clinical trial. Animals: 63 dogs with relapsed or refractory lymphoma. Procedures: Chemotherapy was administered in 21-day cycles. A combination of temozolomide and an anthracycline (doxorubicin or dactinomycin) was administered to 21 dogs and a combination of dacarbazine and an anthracycline was administered to 42 dogs. Efficacy and toxicoses were assessed. Results: Thirteen of the 18 (72%) dogs treated with the temozolomide-anthracycline combination and 25 of the 35 (71%) dogs treated with the dacarbazine-anthracycline combination had a complete or partial response. Median duration of response to rescue chemotherapy was 40 days (range, 0 to 217 days) for dogs in the temozolomide group and 50 days (range, 0 to 587 days) for dogs in the dacarbazine group. The incidence of high-grade hematologic toxicoses was significantly higher among dogs in the dacarbazine group than among dogs in the temozolomide group, but the incidence of gastrointestinal tract toxicoses was not significantly different between groups. There were no significant differences between groups in regard to proportion of dogs with a complete or partial response, duration of response to rescue chemotherapy, survival time following rescue chemotherapy, or overall survival time. Conclusions and Clinical Relevance: Both combinations had promise in the treatment of dogs with relapsed or refractory lymphoma, although administration of temozolomide was more convenient than administration of dacarbazine and caused fewer hematologic toxicoses.
- Evaluation and comparison of outcomes in dogs with periarticular and nonperiarticular histiocytic sarcomaKlahn, Shawna L.; Kitchell, Barbara E.; Dervisis, Nikolaos G. (American Veterinary Medical Association, 2011-07-01)Objective—To evaluate and compare the outcomes of dogs with periarticular histiocytic sarcoma (PAHS) and histiocytic sarcoma of other anatomic locations (non-PAHS) and identify factors associated with outcome for dogs with PAHS. Design—Retrospective cohort study. Animals—19 dogs with PAHS and 31 dogs with non-PAHS. Procedures—Medical records of dogs with histiocytic sarcoma that underwent definitive local treatment (surgery or radiation), chemotherapy, or a combination of these were reviewed. Patient signalment, clinical signs, staging test results, clinicopathologic data, type of treatment, response, and outcome were collected, and potential risk factors in dogs with PAHS were identified and analyzed for an association with outcome. Results—Dogs with PAHS lived significantly longer than did dogs with non-PAHS, with an overall median survival times of 391 (range, 48 to 980) and 128 (range, 14 to 918) days, respectively, despite the presence of suspected metastasis at diagnosis in 13 of 19 dogs with PAHS. Dogs with PAHS without evidence of metastasis at diagnosis lived significantly longer than did dogs with PAHS with evidence of metastasis, with median survival times of 980 (range, 83 to 980) and 253 (range, 48 to 441) days, respectively. Administration of prednisone in dogs with PAHS was associated with a significantly shorter time to tumor progression (TTP) and increased risk of tumor progression and death. Conclusions and Clinical Relevance—Results indicated that dogs with PAHS may have a favorable outcome independent of metastatic status when treated with chemotherapy or aggressive multimodal treatment. The concurrent administration of prednisone may be a negative predictive factor for survival time and TTP in dogs with PAHS.
- Evaluation of ifosfamide salvage therapy formetastatic canine osteosarcomaBatschinski, K.; Dervisis, Nikolaos G.; Kitchell, Barbara E. (Wiley-Blackwell, 2014-12-01)A retrospective study was performed to assess toxicity and response rate of ifosfamide salvage treatment for dogs diagnosed with metastatic osteosarcoma (OSA). Dogs diagnosed with OSA and previously treated with standard chemotherapy were included in the study. Nineteen dogs met the inclusion criteria, and 17 dogs were evaluable for response. Ifosfamide doses ranged from 375 to 425 mg m−2 (median dose 375 mg m−2), with a median of two doses administered per dog (range 1–7 doses). The overall response to ifosfamide was 11.8% [complete response (CR)=1/17, partial response (PR)=1/17, stable disease (SD)=2/17, progressive disease (PD)=13/17]. Two dogs were hospitalized due to ifosfamide toxicosis. The median survival duration from the first dose of ifosfamide to death was 95 days. Ifosfamide was well tolerated, but minor anti-tumour activity was observed.
- Measurement of serum carboxyterminal cross-linked telopeptide of type I collagen concentration in dogs with osteosarcomaHintermeister, John G.; Jones, Pamela D.; Hoffmann, Walter E.; Siegel, Arthur M.; Dervisis, Nikolaos G.; Kitchell, Barbara E. (American Veterinary Medical Association, 2008-11-01)Objective—To evaluate the usefulness of carboxyterminal cross-linked telopeptide of type I collagen (ICTP) concentrations for screening dogs for the presence of osteosarcoma. Sample Population—32 client-owned dogs with osteosarcoma (27 dogs with osteosarcoma of the appendicular skeleton and 5 dogs with osteosarcoma of the axial skeleton) and 44 non–tumor-bearing control dogs. Procedures—Serum was obtained from blood samples collected from dogs with osteosarcoma and from clinically normal dogs. The serum ICTP concentration was determined by use of a commercially available radioimmunoassay for ICTP. Results—Mean ± SD serum ICTP concentration in the tumor-bearing dogs was 7.32 ± 2.88 ng/mL, and in clinically normal dogs, it was 6.77 ± 2.31 ng/mL; values did not differ significantly. Mean serum ICTP concentration in dogs with appendicular osteosarcoma, compared with that of clinically normal dogs, was not significantly different. Mean serum ICTP concentration in dogs with axial skeletal tumor location was 10.82 ± 2.31 ng/mL, compared with a value of 6.73 ± 2.28 ng/mL in dogs with appendicular osteosarcoma. Conclusions and Clinical Relevance—On the basis of the results of this study, serum ICTP concentrations are not a clinically useful screening tool for the detection of appendicular osteosarcoma in dogs. Despite the observation that serum ICTP concentration was higher in dogs with axial osteosarcoma than in clinically normal dogs, serum ICTP concentration determination is not a suitable screening test for osteosarcoma.
- Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with CarcinomasMartinez-Ruzafa, I.; Dominguez, Pedro A.; Dervisis, Nikolaos G.; Sarbu, L.; Newman, R. G.; Cadile, Casey D.; Kitchell, Barbara E. (Wiley-Blackwell, 2009-05-01)Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas. Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats. Animals: Twenty cats with spontaneously occurring carcinomas. Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days. Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1–6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5–10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs). Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored.
- Treatment-related toxicities in tumor-bearing cats treated with temozolomide alone or in combination with doxorubicin: a pilot assessmentGagnon, Jerome; Dervisis, Nikolaos G.; Kitchell, Barbara E. (SAGE, 2012-08-01)A retrospective study assessing treatment-related toxicities in tumor-bearing cats treated with temozolomide (TMZ) alone or in combination with doxorubicin was conducted. TMZ was administered orally once a day for 5 days every 3 weeks at a dose of 20 mg/cat. Tumor response was evaluated with standard World Health Organization criteria and toxicity was monitored using veterinary co-operative oncology group–common terminology criteria for adverse events (VCOG—CTCAE) criteria. Ten tumor-bearing cats with various types of malignancies were treated with TMZbased chemotherapy. Eight cats were evaluable for response. Two cats achieved a complete response, one achieved stable disease and five achieved a partial response. Four grade III and one grade IV hematological toxicities, and one grade IV gastrointestinal toxicity were observed. Four cats were euthanased as a result of apparent toxicity. One cat was euthanased as a result of severe and prolonged myelosuppression with fever. Three were euthanased for grade III pleural and pericardial effusions. Effusion was seen in cats treated with higher cumulative dose of TMZ (P = 0.0046). Planned additional case accrual was discontinued because of unacceptable levels of toxicity despite evidence of efficacy in some of the cats. Additional investigation is needed to elucidate this unexpected apparent cumulative toxicity.