A retrospective evaluation of doxorubicin-based chemotherapy for dogs with right atrial masses and pericardial effusion.

OBJECTIVE: To report the outcome of doxorubicin-based chemotherapy as the sole treatment for dogs with echocardiographically identified right atrial masses and pericardial effusion. METHODS: A retrospective study of case records of dogs with right atrial masses treated with doxorubicin. Dogs were excluded from the study if they had any type of surgery performed such as pericardiectomy or right atrial mass resection, or if their chemotherapy protocol did not include doxorubicin. The data collected included signalment, history, physical examination findings, diagnostic test results and long-term survival. RESULTS: Dogs with right atrial masses and pericardial effusion that received doxorubicin-based chemotherapy alone had a median survival of 139 · 5 days (range 2 to 302 days). Chemotherapy side effects were frequent but mild. CLINICAL SIGNIFICANCE: Doxorubicin-based chemotherapy alone appears to be a viable treatment option for dogs with echocardiographically identified right atrial masses and pericardial effusion.

Phase II open-label study of single-agent hydroxyurea for treatment of mast cell tumours in dogs.

This prospective study evaluated the efficacy and safety of hydroxyurea (HU) in dogs with measurable mast cell tumours (MCTs). Dogs were treated with HU at 60 mg kg(-1)per os q24h for 14 days then 30 mg kg(-1) q24h thereafter or until MCT recurrence. Forty-six dogs were enrolled. The overall response rate was 28%. Two dogs had a complete response (CR) for 256 and 448 days, respectively. Eleven dogs had a partial response for a median duration of 46 days (range, 28-189 days). Grade 2 to 4 neutropenia occurred in eight dogs and grade 4 thrombocytopenia in two. Grade 3-4 anaemia occurred in seven dogs; overall, there was a significant decrease in haematocrit after treatment with HU. The median drop in haematocrit was 10%. This study demonstrated that HU has activity in the treatment of MCTs with mild anaemia being the primary adverse event.

Evaluation of dexamethasone as a chemoprotectant for CCNU-induced bone marrow suppression in dogs.

In mice and people, administering corticosteroids before chemotherapy can reduce the severity of myelosuppression without reducing antitumour effects. This study investigated whether pretreatment with dexamethasone would reduce the incidence of grade 4 neutropenia in dogs receiving CCNU. Twenty-five dogs received dexamethasone [0.1 mg kg(-1) per os (PO) every 12 h] for 5 days and on the sixth day received CCNU (90 mg m(-2) PO). Historical dogs (n = 67) received CCNU alone (90 mg m(-2) PO). Forty-five percent of historical dogs had grade 4 neutropenia, while 64% of dogs pretreated with dexamethasone had grade 4 neutropenia (P = 0.16). Dexamethasone plasma levels were quantified by enzyme-linked immunosorbent assay in three healthy dogs. Peak plasma concentrations after a single oral 0.1-mg kg(-1) dose were <80 ng mL(-1), the minimum level associated with chemoprotective effects of dexamethasone in people. Pretreatment with dexamethasone did not reduce the incidence of grade 4 neutropenia in dogs receiving CCNU.

Efficacy of combination chemotherapy for treatment of gastrointestinal lymphoma in dogs.

BACKGROUND: Chemotherapy for multicentric canine lymphoma has favorable results. The gastrointestinal (GI) tract is the most common extranodal site of canine lymphoma, but there have been no prospective studies to determine outcome when dogs with GI lymphoma are treated with chemotherapy. HYPOTHESIS: Treatment with a multiagent chemotherapy protocol is associated with a poor outcome in dogs with GI lymphoma. ANIMALS: Eighteen dogs with histologically confirmed GI lymphoma. METHODS: Prospective clinical trial in which dogs with GI lymphoma were treated with a 20-week combination chemotherapy protocol consisting of induction and consolidation phases. RESULTS: Thirteen dogs had primary GI lymphoma and 5 had multicentric lymphoma with GI involvement. The majority of the lymphomas (63%) were of T-cell origin. Overall remission rate was 56%; 9 dogs achieved a complete remission for a median of 86 days (range, 22-420 days) and 1 dog achieved a partial remission for 26 days. Overall median survival time was 77 days (range, 6-700 days). Dogs that failed to achieve a remission (10 versus 117 days; P= .002) or had diarrhea at initial presentation (70 versus 700 days; P < .001) had shorter survival times. CONCLUSION AND CLINICAL IMPORTANCE: The response and survival of dogs with GI lymphoma treated with multiagent chemotherapy is poor but long-term survival is possible.

Phase I dose escalation of single-agent vinblastine in dogs.

BACKGROUND: Vinblastine (VBL) is commonly used in dogs at a dosage of 2.0 mg/m2. The minimal toxicity observed at this dosage indicates that higher dosages might be well tolerated. HYPOTHESIS: The maximum tolerated dosage (MTD) for a single VBL treatment is higher than the previously published dosage of 2.0 mg/m2. ANIMALS: Twenty-three dogs with lymphoma or cutaneous mast cell tumors. METHODS: Dogs received 1 single-agent VBL treatment IV. The starting dosage was 3.0 mg/m2, and dosages were increased in increments of 0.5 mg/m2 in cohorts of 3 dogs. Hematologic toxicity was assessed with weekly CBCs. Gastrointestinal toxicity was assessed from medical histories from owners. Once the MTD was determined, additional dogs were treated with VBL at that dosage. Dogs whose cancers responded to VBL continued to receive treatments q2-3 weeks. RESULTS: VBL dosages ranged from 3.0 to 4.0 mg/m2. Neutropenia was the dose-limiting toxicity, with the nadir identified 7 days after treatment and resolving by 14 days after treatment. The MTD was 3.5 mg/m2. Sixteen dogs were treated at this dosage, and 3 experienced severe toxicity characterized by asymptomatic grade 4 neutropenia, febrile grade 4 neutropenia, and death. Gastrointestinal toxicity was mild and self-limiting. Preliminary evidence of antitumor activity was identified in 2 of 12 dogs with lymphoma treated at the MTD. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs, single-agent VBL is well tolerated at a dosage of 3.5 mg/m2 IV. At this dosage, the minimum safe treatment interval is q2 weeks, and adjunct treatment with prophylactic antibiotics should be considered.

Prophylactic trimethoprim-sulfadiazine during chemotherapy in dogs with lymphoma and osteosarcoma: a double-blind, placebo-controlled study.

BACKGROUND: The administration of chemotherapy is associated with risk for morbidity. Management of chemotherapy-related morbidity in veterinary oncology has been primarily supportive. HYPOTHESIS: The purpose of this study was to evaluate the effect of prophylactic antimicrobial use on chemotherapy-associated morbidity in dogs with lymphoma or osteosarcoma. ANIMALS: Dogs presenting with histologically confirmed osteosarcoma or lymphoma were eligible. METHODS: Patients were randomized to receive placebo or trimethoprim-sulfadiazine for 14 days after their first doxorubicin chemotherapy. Both owner and clinician were blinded with respect to treatment. Patient assessment included CBC, physical examination and performance, and toxicosis grading on days 7 and 14. Investigated outcomes were hospitalization, suspicion of infection, gastrointestinal toxicity, neutropenia, nonhematologic toxicity, and quality of life. RESULTS: Seventy-three dogs were enrolled; 34 had osteosarcoma, and 39 had lymphoma. Dogs receiving trimethoprim-sulfadiazine (n = 36) had a significantly reduced hospitalization rate (P = .03), nonhematologic toxicity (P = 0.039), grade 2-4 nonhematologic toxicity (P < .0001), grade 2-4 gastrointestinal toxicity (P = .007). and altered performance (P = .015). By group, dogs with osteosarcoma (n = 34) that received the antimicrobial experienced fewer occurrences of nonhematologic toxicity (P = .02) and less severe nonhematologic toxicity (P = .038). Dogs with lymphoma (n = 39) had significant reductions in the occurrence of hospitalization (P = .035), severity of nonhematologic toxicity (P = .036), and alterations of performance (P = .015). CONCLUSIONS: The use of prophylactic trimethoprim-sulfadiazine has benefit in reducing morbidity in dogs with osteosarcoma or lymphoma during the first 14 days after treatment with doxorubicin.

Treatment of vascular and soft-tissue sarcomas in dogs using an alternating protocol of ifosfamide and doxorubicin.

A retrospective analysis was done to assess the toxicity and efficacy associated with an alternating chemotherapy protocol of ifosfamide (375 mg m(-2)) and doxorubicin (30 mg m(-2)) for adjuvant treatment of 39 dogs with sarcomas. Twelve dogs had various soft-tissue sarcomas and 27 dogs had hemangiosarcoma (HSA). Complete blood counts were evaluated 7 days after the first dose of ifosfamide and doxorubicin. One dog had grade 4 neutropenia (<500 microL(-1)) after treatment with ifosfamide and one dog had grade 3 neutropenia (500-1000 microL(-1)) after treatment with doxorubicin. One dog treated with doxorubicin was hospitalized for 24 h due to vomiting. The median survival time (ST) for the 27 dogs with HSA treated by surgery and with doxorubicin/ifosfamide was 149 days (mean 366 days). Although the protocol of alternating ifosfamide and doxorubicin was well tolerated, it failed to result in a statistically significant improvement in the ST when compared to a historical population of dogs with stage 2 splenic HSA treated by surgery alone.

A combination chemotherapy protocol with MOPP and CCNU consolidation (Tufts VELCAP-SC) for the treatment of canine lymphoma.

A chemotherapy protocol using a consolidation phase of alkylating agents was used for treating 94 dogs with lymphoma. Fifty-seven percent of dogs were in stage V, 63% were ill and 38% had T-cell lymphoma. The complete remission (CR) rate was 70% and is comparable to results achieved with previously published chemotherapy protocols. Anorexia predicted the remission; of the 40 dogs without anorexia, 35 (88%) achieved CR whereas of 52 dogs with anorexia, 30 (58%) achieved CR. Median first CR duration was 168 days and 1- and 2-year CR rates were 17.4 and 15.5%, respectively. Platelet count affected length of first CR, with a 53.2% reduced chance of coming out of remission with each log increase in platelet count. Median survival time was 302 days. One and 2-year survival rates were 44 and 13%, respectively. Anorexia and no dose reduction of any drug were independent negative variables. Of 93 dogs with toxicity data, 65 dogs (70%) required a dose reduction. Cyclophosphamide was most commonly reduced with reductions in 31 (38%) of 82 dogs. A dose reduction was significantly more likely in dogs with B-cell lymphoma than in those with T-cell lymphoma.