A combination chemotherapy protocol with dose intensification and autologous bone marrow transplant (VELCAP-HDC) for canine lymphoma

Twenty-eight dogs with lymphoma were treated with a 12-week, 5-drug chemotherapy protocol concluding with high-dose cyclophosphamide supported by autologous bone marrow transplants. A dose escalation design was used to determine the maximum tolerated cyclophosphamide dose (MTD) in this setting. Three cyclophosphamide dose levels were given: 300 mg/ m2 IV (groupl, 3 dogs), 400 mg/m2 IV (group 2, 12 dogs), and 500 mg/m2 IV (group 3, 13 dogs); and the MTD was 500 mg/m2 IV. Toxicity was common but mild, and the dose-limiting toxicity was myelosuppression, specifically neutropenia. No dog died as a result of treatment-related toxicity. One dog in group 3 developed fever, neutropenia, and presumed sepsis and responded promptly to routine management. No other dog required hospitalization. Lower stage and higher cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest dose [group 3]) compared with the lower doses combined (groups 1 and 2) were significantly associated with longer remission duration (all P < .0001). Median remission duration for dogs in group 3 was 54 weeks, compared with 21 weeks for dogs in groups 1 and 2 combined. Factors associated with longer survival time were lower stage (P = .042) and higher cyclophosphamide dose (both increasing dose [study groups 1-3], and the highest dose [group 3] compared with the lower doses combined [groups 1 and 2]) (P = .027). Median survival time for dogs in group 3 was 139 weeks, compared with 43 weeks and 68 weeks for dogs in groups 1 and 2, respectively.     

Canine multicentric lymphoma 2: Comparison of response to two chemothera-peutic protocols

This paper describes the chemotherapeutic response of 90 cases of canine multicentric lymphoma. All the dogs were treated with a combination protocol using cyclophosphamide, vincristine and prednisolone. Forty-seven dogs received additional intravenous cytosine arabinoside on the first four days of treatment. Eighty-eight per cent of all cases had shown either a complete or partial response to this treatment at six weeks from the start of treatment and the overall mean survival time was 37 weeks (SD = 35.8). There was no significant difference in response or survival rates between the two treatment groups. The age and sex of the patient, the clinical stage of the disease and previous treatment with corticosteroids were all analysed to determine whether these parameters were of prognostic significance. Those dogs in clinical stages 4 and 5 carried a worse prognosis than those in stages 1 to 3. Previous treatment with corticosteroids adversely affected both tumour response and patient survival rates.     

Evaluation of once daily treatment with cyclosporine for anal furunculosis in dogs

Twenty-four dogs with anal furunculosis were treated with cyclosporine once daily for 13 weeks at dosages of 1.5, 3.0, 5.0 or 7.5 mg/kg, and re-examined after six and 12 months. After 13 weeks the disease in six of the dogs was in remission, 11 were controlled or improved and seven had failed to respond. The response of the dogs given the highest dose was significantly better than the response of the other groups taken together (P < 0.014), and better than the responses of the groups given 1.5 mg/kg and 5 mg/kg (P < 0.05). The dogs improved clinically during the treatment, most rapidly during the first five weeks. Of the six dogs that were in remission after 13 weeks, three relapsed after one, two and six months. The 11 dogs that were improved or controlled after 13 weeks were either left untreated or were continued on cyclosporine medication for one to three months at a dosage of 1.5 to 7.5 mg/kg; the disease went into remission in four cases and remained controlled in the other seven, but four of the 11 cases relapsed during the 12 months following the treatment. The side effects observed included increased coat turnover and transient vomiting.     

Treatment of canine lymphoma with COPLA/LVP

Seventy-five dogs with cytopathologically or histopathologically confirmed lymphoma received L-asparaginase, vincristine, cyclophosphamide, prednisone, and doxorubicin (COPLA) induction followed by chlorambucil, vincristine, and prednisone (LVP) maintenance between January 1994 and June 1997. Toxicity was evaluated using the National Cancer Institute (NCI) toxicity criteria. Age, weight, sex, and response were evaluated for prognostic significance against first remission duration. A complete response (CR) was obtained in 61 (80%) dogs, a partial response (PR) was obtained in nine (12%) dogs, and no response (NR) was obtained in five (8%) dogs. The median first remission duration was 25 weeks, with 17% and 5% of the dogs in remission at one and two years, respectively. Observed toxicity was low, with 84% of dogs given an NCI score of 1 or 2. Median survival time for dogs achieving CR was 36 weeks versus four weeks for those achieving PR or NR.     

Assessment of disease severity and outcome of dietary, antibiotic, and immunosuppressive interventions by use of the canine IBD activity index in 21 dogs with chronic inflammatory bowel disease

Recently, the canine IBD activity index (CIBDAI) was developed for evaluation of the severity of illness, therapeutic strategies, and efficacy of therapy.The aim of the present study was to assess the severity of illness and the therapeutic strategy in dogs with IBD by the use of CIBDAI, serum albumin concentration, and histologic score (HPEG). Furthermore the use of CIBDAI and the efficacy of therapy in a prospective study during a 3 month treatment period were evaluated. Twentyone dogs with inflammatory bowel disease (lymphocytic-plasmacytic enteritis and enterocolitis) were examined in this study. In 11 dogs with IBD the severity of illness was assessed as low, according to CIBDAI and HPEG (CIBDAI score 4 or between 5 and 10 with HPEG score between 1 and 1.5). Six dogs were treated with hypoallergenic diet (Group D), five dogs were treated with hypoallergenic diet and metronidazole (15.6-22,3 mg/kg/day) (Group M). In 10 dogs with IBD the severity of illness was assessed as high (CIBDAI <10, or CIBDAI between 5 and 10 with HPEG score between 2 and 3 or hypoalbuminemia (< or = 2.5 g/dl)). This group (Group I) was treated with immunosuppressive therapy.Treatment consisted of prednisolone (n=10; 0.9-2 mg/kg/day), azathioprine (n=5; 0.9-2.3 mg/kg/day), sulfasalazine (n=4; 18.2-25 mg/kg/day) and hypoallergenic diet (n=10). Efficacy of therapy was evaluated prospectively 3 times in a 12 weeks treatment period. Remission (CIBDAI score < 4) indicated good therapeutic response, chronic or recurrent disease (CIBDAI score persistent or recurrent > or =4) indicated poor therapeutic response. Age, CIBDAI score and HPEG score were significantly different in IBD dogs with low severity of illness (age: median 60 months; CIBDAI score: median 5; HPEG score: median (1) and IBD dogs with high severity of illness (age: median 90 months; CIBDAI score: median 9.5; HPEG score: median 2.25) (p = 0.0101 and p = 0.0099, respectively). The presence of hypoalbuminemia was not significantly different between these two groups (p = 0.3108). There was no significant correlation between CIBDAI score and serum albumin concentration (r = 0.0394; p = 0.0802) or between CIBDAI score and HPEG score (r = 0.2587; p = 0.2574). In the treatment groups, HPEG score was only significantly different between D-group and group I (p < 0.01). The CIBDAI score decreased significantly in group I after 4 weeks of treatment (median 4th week: 3; p < 0.05), and in the D-group after 8 weeks of treatment (median 8" week 1; p < 0.05). No significant decrease of CIBDAI score was seen in the M-group (median 12th week: 1.75; p > 0.05). All dogs in group D, four of five dogs in group M, and six from ten dogs in group I went into remission. Poor therapeutic response (1 dog in group M and 5 dogs in group I; one dog died) was seen in 6 dogs, where as 15 dogs showed good therapeutic response. There was no significant association between efficacy of therapy and age (p = 0.8455), CIBDAI score (p = 0.3293), or serum albumin concentraton (p = 0.8455). Poor therapeutic response was weekly associated with HPEG score > or =2 (p = 0.0635). Using CIBDAI in dogs with IBD as a single parameter to assess the severity of illness and the therapeutic response, misinterpretations are possible.The assessment of the severity of illness by the combination of CIBAI, HPEG, and serum albumin concentration is leading to adaequate therapeutic results. Dogs with low grade IBD benefit from hypoallergenic diet, whereas dogs with high grade IBD benefit from immunosuppressive therapy. The effect of antibiotic treatment is questionable.     

Pradofloxacin in the treatment of canine deep pyoderma: a multicentred, blinded, randomized parallel trial

A multicentre, randomized, blinded study compared the efficacy of pradofloxacin with that of a combination of amoxycillin/clavulanic acid in the treatment of deep pyoderma in dogs. Dogs with clinical lesions of deep pyoderma and a positive bacterial culture were included in the study. At each visit, they were evaluated with lesion, pruritus and general condition scores. Dogs were treated either with pradofloxacin at 3 mg kg-1 once daily or with amoxycillin at 10 mg kg-1 and clavulanic acid at 2.5 mg kg-1 twice daily and evaluated weekly for 3 weeks and every 2 weeks thereafter until 2 weeks past clinical remission. Maximal treatment duration was 9 weeks, and maximal evaluation period was 11 weeks. Of the 56 dogs treated with pradofloxacin (group 1), 48 dogs (86%) achieved clinical remission, four dogs improved, four dogs did not respond and a recurrence of clinical signs was not seen in any patient after 11 weeks. Of the 51 dogs treated with amoxycillin/clavulanic acid (group 2), 37 dogs achieved clinical remission (73%), three dogs showed improvement, five dogs showed no response and in six dogs, clinical signs recurred within 2 weeks of cessation of therapy. These results indicate that pradofloxacin is an efficacious therapy comparable to amoxycillin/clavulanic acid for deep bacterial pyoderma in dogs.     

Influence of asparaginase on a combination chemotherapy protocol for canine multicentric lymphoma

Combination chemotherapy is superior to single-agent chemotherapy for treating canine lymphoma, but the effect of each drug on efficacy remains unknown. By comparing 34 dogs treated with a modified cyclophosphamide, vincristine, prednisone (COP) chemotherapy protocol and 42 dogs given asparaginase in the induction phase of the same protocol, the effect of asparaginase on the chemotherapeutic protocol was determined. Both groups were compared based on clinical response at 2 weeks and 6 weeks, and on the progression-free interval. Asparaginase did not significantly increase the likelihood of a clinical remission or prolong the initial progression-free interval in the dogs studied.     

Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma

OBJECTIVE: To compare response rates and remission and survival times in dogs with lymphoma treated with a continuous, multiagent, doxorubicin-based chemotherapeutic protocol or with a short-term single-agent protocol incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial. ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a chemotherapeutic protocol consisting of L-asparaginase, vincristine, cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs treated with the single-agent protocol had a complete remission. Dogs with lymphoma classified as substage相似文献   

Efficacy and Toxicity of Doxorubicin/Cyclophosphamide Maintenance Therapy in Dogs with Multicentric Lymphosarcoma

Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P less than 0.04). Nineteen dogs were evaluable for toxicity. Dose-limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol.     

Is Maintenance Chemotherapy Appropriate for the Management of Canine Malignant Lymphoma?

A retrospective study was conducted between two groups of dogs with histopathologically diagnosed multicentric malignant lymphoma to determine if treatment with either short-term or continuous chemotherapy resulted in a significant difference in first-remission length or survival time. One group was treated with single agent, short-term (three cycles) of doxorubicin. Dogs obtaining complete remission while receiving doxorubicin were given no further chemotherapy. The other group received combination agent, long-term chemotherapy consisting of cyclophosphamide, vincristine sulfate, and prednisone (COP). Dogs obtaining complete remission on COP by the end of 6 weeks were given maintenance chemotherapy of cyclophosphamide, prednisone and methotrexate. One hundred and five dogs were treated. Thirty-eight dogs received doxorubicin and 67 received COP. All dogs were evaluated at 6 weeks for response to chemotherapy and followed until death. No significant differences were observed in first-remission length or survival time when comparing dogs treated with either short-term doxorubicin or long-term COP (P greater than 0.05). Sex, weight, age, clinical stage, performance status, histopathologic cell type, and grade were not significant factors for determining the responsiveness to either chemotherapy protocol. However, within either treatment group, significant differences in first-remission length were observed in dogs evaluated histopathologically by the Keil and NCI working formulation and in survival time when evaluated by performance status (P less than 0.05).     

The immunopathogenesis of flea allergy dermatitis in dogs, an experimental study

In this study, we investigated the development of clinical disease and immune responses in the development of an experimental model of flea allergy dermatitis. Dogs were randomly divided into four treatment groups and were infested with fleas on two different feeding schedules (continuous and episodic). Group 1 consisted of four non-exposed dogs (negative controls) and Group 2 consisted of six dogs exposed to fleas continually. Groups 3 and 4 consisted of 14 dogs each that were exposed to fleas on an episodic schedule (two consecutive days every other week for 12 weeks). Group 4 also received intraperitoneal injections of a low dose of lectin (ricin) with immunomodulatory properties. The purpose of Group 4 was to investigate the effects of ricin on enhancing the development of clinical signs, flea antigen-specific IgE levels and altering the number of CD4+ and CD8+ T cell subsets in peripheral blood. Clinical signs developed in all flea exposed dogs, however, the dermatology lesion scores were less and shorter in duration for continuously exposed dogs compared to episodic exposed dogs, independent of ricin treatment. Lesion development was concentrated in the flea triangle and consisted principally of erythema, followed by alopecia, excoriation, papules, and crusts. CD4+ and CD8+ lymphocyte subsets or IgE levels were not altered by ricin treatment. Flea antigen-specific IgE values were highest in dogs exposed to fleas on a continuous basis compared to those episodically exposed. A greater percentage of clinical responder dogs with negative flea-specific IgE titers or negative intradermal test (IDT) were present in the episodic exposure groups than in the continuous exposure group. IgE titers corresponded slightly better with clinical responders than the IDT. The agreement between the IgE titers and IDT was good (weighted K = 0.67). Histopathology of skin samples were consistent with a Type I hypersensitivity. In conclusion, we were able to develop a model of flea allergy dermatitis by experimentally exposing dogs to fleas on an episodic and continuous feeding schedule. In this study, continuously exposed dogs did not develop immunotolerance, and ricin did not enhance the development of FAD.     

Pharmacokinetics of cyclophosphamide after oral and intravenous administration to dogs with lymphoma

Background: Cyclophosphamide is an alkylating chemotherapeutic drug administered IV or PO. It is currently assumed that exposure to the active metabolite, 4‐hydroxycyclophosphamide (4‐OHCP), is the same with either route of administration.

Objectives:

To characterize the pharmacokinetics of cyclophosphamide and 4‐OHCP in dogs with lymphoma when administered PO or IV. Animals: Sixteen client‐owned dogs with substage A lymphoma were enrolled in the study. Eight dogs received cyclophosphamide IV and 8 received it PO. Methods: Prospective randomized clinical trial was performed. Blood was collected from each dog at specific time points after administration of cyclophosphamide. The serum was evaluated for the concentration of cyclophosphamide and 4‐OHCP with mass spectrometry and liquid chromatography. Results: Drug exposure to cyclophosphamide measured by area under the curve (AUC)_0–inf is significantly higher after intravenous administration (7.14 ± 3.77 μg/h/mL) compared with exposure after oral administration (P‐value < .05). No difference in drug exposure to 4‐OHCP was detected after IV (1.66 ± 0.36 μg/h/mL) or PO (1.42 ± 0.64 μg/h/mL) administered cyclophosphamide. Conclusions and Clinical Importance: Drug exposure to the active metabolite 4‐OHCP is equivalent after administration of cyclophosphamide either PO or IV.     

Evaluation of treatment with doxorubicin and piroxicam or doxorubicin alone for multicentric lymphoma in dogs

OBJECTIVE: To evaluate the antitumor and toxic effects of treatment with doxorubicin combined with piroxicam or doxorubicin alone for multicentric lymphoma in dogs. DESIGN: Nonrandomized clinical trial. ANIMALS: 75 dogs with multicentric lymphoma. PROCEDURE: 33 dogs were treated with doxorubicin (30 mg/m2, IV, q 21 d, for 3 doses) and piroxicam (0.3 mg/kg [0.14 mg/lb], PO, q 24 h); results were compared with a historical control group of 42 dogs treated with doxorubicin (30 mg/M2, IV, q 21 d, for 3 doses) alone. Results-The percentages of dogs that had remission with doxorubicin-piroxicam treatment (79%) or doxorubicin treatment alone (74%) were not significantly different. Median duration of first remission was 130 days with doxorubicin-piroxicam and 147 days with doxorubicin alone; these values were not significantly different. Severe toxicosis was observed in 22% of dogs treated with doxorubicin-piroxicam and 17% of dogs treated with doxorubicin alone. CONCLUSIONS AND CLINICAL RELEVANCE: Both treatment protocols were efficacious and well tolerated. The doxorubicin-piroxicam treatment was no more effective regarding response rate, remission duration, or survival duration, compared with the control group treated with doxorubicin alone.     

Doxorubicin and cyclophosphamide for the treatment of canine lymphoma: a randomized,placebo‐controlled study*

Median survival times (STs) for doxorubicin‐treated canine lymphoma range from 5.7 to 9 months. Because dogs treated with multi‐agent protocols have longer STs, we sought to evaluate whether adding cyclophosphamide would improve outcome in canine lymphoma patients while maintaining an acceptable level of toxicity. Thirty‐two dogs with stage III–V multicentric lymphoma were treated with doxorubicin every 3 weeks for five total cycles and prednisone at a tapering dose for the first 4 weeks. Dogs were randomized to receive either cyclophosphamide or placebo concurrently. Seventeen dogs received doxorubicin and placebo, while 15 dogs received doxorubicin and cyclophosphamide. Response, toxicity, progression‐free interval (PFI) and ST were evaluated. The combination of doxorubicin and cyclophosphamide was well tolerated, causing no increase in adverse events over doxorubicin alone. Despite a numeric improvement in outcome in cyclophosphamide treated dogs, the addition of cyclophosphamide did not result in statistically improved response rate, PFI or ST.     

A comparison of two pamidronate dosing protocols on bone turnover in normal dogs and dogs with osteosarcoma

Introduction: Dogs with appendicular osteosarcoma (OSA) excrete higher concentrations of urine cross‐linked N‐telopeptide of type I collagen (NTx) than normal dogs. NTx is a specific biochemical marker of osteoclastic activity. Pamidronate is a bone‐modulating agent that exerts potent inhibitory effects on osteoclasts. The use of pamidronate is currently being evaluated for the management of osteolytic bone pain in dogs with appendicular osteosarcoma. Despite pamidronate's increasing usage in veterinary oncology, optimal dosing has yet to be determined. Commonly utilized dosages range from 1–2 mg/kg, given intravenously (IV) as a 2‐hour constant rate infusion every 28 days. The purpose of this prospective study was to compare the biological activity of two pamidronate doses (1 mg/kg vs. 2 mg/kg) in the suppression of urine NTx excretion in normal dogs and dogs with appendicular osteosarcoma. Methods: Seventeen OSA dogs receiving single‐agent pamidronate as palliative therapy were evaluated. Group 1A (n = 10) received a dose of 1 mg/kg and group 2A (n = 7) received a dose of 2 mg/kg IV. Urine NTx level were measured at day 0 and 28 using a commercial ELISA (Ostex International). Urine NTx level were also measured in 6 normal dogs: Group 1B (n = 3) received a dose of 1 mg/kg and group 2B (n = 3) received a dose of 2 mg/kg. In normal dogs, urine NTx levels were recorded weekly for six consecutive weeks. Results: In dogs with osteosarcoma, greater reductions in urine NTx excretion from baseline values were demonstrated at 2 mg/kg versus 1 mg/kg (57% and 23%, respectively). Likewise, in normal dogs, urine NTx excretion was suppressed to a greater extent with a dosage of 2 mg/kg versus 1 mg/kg (69% and 23%, respectively). Conclusion: Pamidronate possesses biologic activity in both normal dogs and in dogs with osteosarcoma, as assessed by reductions in urine NTx excretion. Based upon reductions in urine NTx excretion, a dosage of 2 mg/kg appears more effective than 1 mg/kg.     

Combination chemotherapy with vincristine, cyclophosphamide, and prednisone producing long-term remission of a transplanted canine lymphoma.

Lymphoma developed in 6 neonatal pups inoculated with 1.0 to 2.06 X 10(9) cells of the 2nd in vivo passage of a canine lymphoma. Three to 4 weeks later (or 8 weeks after the pups had been inoculated), 3 of the 6 pups were started on a chemotherapeutic regimen consisting of vincristine, prednisone, and cyclophosphamide. Twelve to 19 days after combination chemotherapy was started, clinically efident lymphoma disappeared in the 3 pups. Period of treatment was 49 to 84 days. The dogs remained healthy and lymphoma was in complete remission approximately 2 years later. The 3 nontreated pups, used as controls, died of generalized lymphoma 45 to 86 days after inoculation. Seemingly, chemotherapy eradicated the bulk of the tumor, and the host immune response was capable of eliminating residual neoplastic cells. Also, transplanted canine lymphoma seems amenable to treatment and may be curable with combination chemotherapy--thus possibly serving as an experimental therapeutic model.     

Investigation of the interaction between buprenorphine and sufentanil during anaesthesia for ovariectomy in dogs

OBJECTIVE: To investigate the effect of buprenorphine pre-treatment on sufentanil requirements in female dogs undergoing ovariectomy. STUDY DESIGN: Randomized, 'blinded', prospective clinical study. ANIMALS: Thirty healthy female dogs referred for ovariectomy. MATERIALS AND METHODS: Dogs were randomly assigned to one of two pre-anaesthetic treatment groups. Those in the buprenorphine group (B) received buprenorphine 20 microg kg(-1) and acepromazine 0.03 mg kg(-1) IM. Control group (C) animals received an equal volume of NaCl 0.9% and acepromazine 0.03 mg kg(-1) IM. The anaesthetic technique was identical in both groups. Pre-anaesthetic medication consisted of intravenous (IV) sufentanil (1.0 microg kg(-1)) and midazolam (0.05 mg kg(-1)) and intramuscular atropine (0.03 mg kg(-1)). Anaesthesia was induced with propofol and maintained with a constant rate infusion of sufentanil (1.0 microg kg(-1) hour(-1)) and with oxygen-isoflurane. Ventilation was controlled mechanically. Ovariectomy was performed using a standard technique. Baseline heart rate (HR) and direct mean arterial blood pressure (MAP) were recorded before the first incision. Increases in HR and MAP of > or =20% over baseline and, or spontaneous ventilation were controlled using IV sufentanil (1.0 microg kg(-1)) repeated after 5 minutes if haemodynamic variables remained elevated or attempts at spontaneous ventilation persisted. Analysis of variance was used to determine group differences in mean and median HR and MAP and to compare the maximum HR and MAP attained during surgery. Poisson regression was used to compare the number of sufentanil injections required in both groups. RESULTS: Group B required 2.46 times more sufentanil injections (p = 0.00487) than dogs in group C to maintain haemodynamic stability and prevent spontaneous ventilation during surgery. Group B dogs also had a significantly higher (p = 0.034) marginal mean of the log maximum MAP (4.756 +/- 0.036) compared with group C (4.642 +/- 0.036). CONCLUSIONS: Pre-treatment with buprenorphine appears to negatively influence the antinociceptive efficacy of intra-operative sufentanil. CLINICAL RELEVANCE: Withholding buprenorphine therapy 6-8 hours before anaesthesia incorporating pure mu receptor agonists is probably advisable. Alternative methods of analgesia should be provided in this period.     

Duration of increased serum alkaline phosphatase activity in dogs receiving different glucocorticoid doses

Exposure to exogenous glucocorticoids can variably increase the serum alkaline phosphatase (alp) activity, however, the duration of this effect in dogs has not been determined. In this study, three groups of ten clinically normal adult dogs were administered different types of glucocorticoids at therapeutic doses. Group 1 received prednisone 1 mg kg day(-1)p.o. for 3 weeks; Group 2 received a single dose of methylprednisone acetate 1.1 mg kg day(-1)s.c.; Group 3 received dexamethasone 0.25 mg kg day(-1)p.o. for 1 week. In Group 1 elevations were statistically significant on days 7, 14 and 21 (P<0.01, P<0.001, P<0.001, respectively). After discontinuing therapy serum alp returned to baseline levels in 7 days. In Group 2, serum alp activity remained significantly elevated for 3 weeks after therapy (P<0.05, P<0.001, P<0.01 on days 7, 14 and 21 respectively). In Group 3, serum alp levels were significantly increased after 1 week of therapy (P<0.001) returning to basal levels 2 weeks after discontinuing glucocorticoid administration. In conclusion, duration of increased serum alp activity was variable and with the protocols assessed a 3-week period for short-acting glucocorticoids and more than 4 weeks for long-acting methylprednisone may be required to return to baseline levels in all dogs.     

Carmustine, vincristine, and prednisone in the treatment of canine lymphosarcoma

A chemotherapeutic protocol using carmustine in combination with vincristine and prednisone was tested in dogs with multicentric malignant lymphosarcoma. Of seven dogs treated, six (85.7%) achieved complete remission. A partial response occurred in one dog. Median survival time was 224 days (mean 386 days), and median duration of remission was 183 days (mean 323 days). Marked neutropenia was observed following carmustine administration. There were no significant alterations in platelets and red blood cell counts during treatment, and no abnormalities attributable to the chemotherapy were found in serum biochemical profiles. Results of this study showed that carmustine is an effective alternative option in the treatment of canine lymphosarcoma.     

Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma

Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi‐institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post‐radiation temozolomide in dogs with chemotherapy‐naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m^?2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post‐radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT.