Actinomycin D as rescue therapy in dogs with relapsed or resistant lymphoma: 49 cases (1999--2006).

OBJECTIVE: To evaluate response rate and disease-free interval in dogs with relapsed or resistant lymphoma treated with actinomycin D, determine hematologic toxicoses, and identify prognostic factors associated with response to treatment. DESIGN: Retrospective case series. ANIMALS: 49 dogs with relapsed or resistant lymphoma. PROCEDURES: Medical records were reviewed for information regarding signalment, physical examination findings, results of diagnostic testing, substage, previous chemotherapy, previous treatment with prednisone, actinomycin D dosage, number of doses administered, response, disease-free interval, and results of CBCs performed after treatment. RESULTS: Actinomycin D was administered at a median dosage of 0.68 mg/m2 (range, 0.46 to 0.72 mg/m2), IV, every 3 weeks for 5 treatments or until disease progression. Twenty-six (53%) dogs received prednisone concurrently. Twenty (41%) dogs had a complete remission, and median disease-free interval in these dogs was 129 days. Thrombocytopenia was the most common hematologic toxicosis (n = 22 [45%]). Concurrent prednisone administration, a shorter duration of first remission, and an increased number of previous chemotherapy agents were significantly associated with a lower likelihood of responding to actinomycin D treatment. Concurrent prednisone administration and an increased number of previous chemotherapy agents were significantly associated with a shorter disease-free interval. CONCLUSION AND CLINICAL RELEVANCE: Results suggested that administration of actinomycin D as a single agent was effective for rescue chemotherapy of dogs with relapsed or resistant lymphoma and that treatment was well tolerated, although mild thrombocytopenia developed commonly.

Lomustine and prednisone as a first-line treatment for dogs with multicentric lymphoma: 17 cases (2004-2005).

OBJECTIVE: To assess response rate, median duration of response, adverse effects, and prognostic factors associated with concurrent administration of lomustine and prednisone as a first-line treatment for dogs with multicentric lymphoma. DESIGN: Retrospective case series. ANIMALS: 17 dogs. PROCEDURES: Medical records were reviewed. Information obtained included signalment, physical examination findings, results of diagnostic testing, stage and substage, initial lomustine and prednisone dosages, and total number of lomustine doses administered. RESULTS: Lomustine was administered at a median starting dosage of 67 mg/m(2), PO, every 21 days until 5 doses were given or disease progression was observed. Prednisone was administered at a median starting dosage of 1.8 mg/kg/d (0.82 mg/lb/d), PO, with dosage tapered during the first month of treatment. Six dogs had a complete response, and 3 had a partial response. Mean and median durations of response were 48.8 and 39.5 days, respectively. Median survival time was 111.2 days. In multivariate analyses, female sex and higher total lomustine dose were significantly associated with a longer disease-free inter-val. Neutropenia was the dose-limiting factor, with 4 dogs developing clinically important neutropenia 1 week after administration of a dose of lomustine. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that concurrent treatment with lomustine and prednisone was well tolerated in dogs with multicentric lymphoma, but findings did not support the use of this combination for first-line treatment of affected dogs.

Evaluation of prognostic factors associated with outcome in dogs with multiple cutaneous mast cell tumors treated with surgery with and without adjuvant treatment: 54 cases (1998-2004).

OBJECTIVE: To evaluate prognostic factors associated with outcome of dogs with multiple cutaneous mast cell tumors (MCTs) treated with surgery with or without adjuvant treatment. DESIGN: Retrospective case series. ANIMALS: 54 dogs with a minimum of 2 simultaneous, histologically confirmed cutaneous MCTs that had been excised and had adequate staging and follow-up data. PROCEDURE: Medical records from 1998 to 2004 were examined. Outcome was assessed with the Kaplan-Meier product-limit method and log-rank analysis. Prognostic factors evaluated included signalment; number, histologic grade, location, size, local recurrence, and de novo development of MCTs; quality of surgical margins; clinical signs at the time of diagnosis; and use of adjuvant treatment. RESULTS: Medical records of 54 dogs with 153 tumors were included. Median follow-up time was 658 days. Median disease-free interval (1,917 days; range, 11 to 1,917 days) and median survival time (1,917 days; range, 14 to 1,917 days) were not yet reached. The 1- year and 2- to 5-year survival rates were 87% and 85%, respectively. The overall rate of metastasis was 15%. Factors that negatively influenced survival time in the univariate analysis included incomplete excision, local recurrence, size > 3 cm, clinical signs at the time of diagnosis, and use of adjuvant treatment. Presence of clinical signs at the time of diagnosis was the only negative prognostic factor for disease-free interval detected in the multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that multiple cutaneous MCTs in dogs are associated with a low rate of metastasis and a good prognosis for long-term survival with adequate excision of all MCTs.

Transurethral resection in the management of urethral and prostatic neoplasia in 6 dogs.

OBJECTIVE: To assess cystoscopic transurethral resection (TUR) for the palliative management of dogs with neoplastic infiltration of the urethra. STUDY DESIGN: Prospective clinical trial. ANIMALS: Six client-owned dogs. METHODS: Cystoscopic examination and electrosurgical TUR were performed in dogs with urination difficulties caused by prostatic or urethral neoplasia. TUR was performed in a retrograde manner in female dogs and antegrade in male dogs via exploratory celiotomy and ventral cystotomy. Cystoscopic examination was used to determine the extent of neoplastic involvement of the urethra. TUR involved piecemeal removal of neoplastic tissue from the urethral lumen using an electrocautery cutting loop. Hemorrhage was controlled with a cystoscopic cauterized roller-ball. In 2 male dogs, intraoperative radiation therapy (IORT) was used to treat both prostatic neoplasia and the sublumbar lymph node bed. Surgical technique, complications, adjuvant treatment, and outcome were recorded. RESULTS: TUR was performed in 3 male dogs with prostatic carcinoma and 2 female dogs with urethral transitional cell carcinoma (TCC). In 1 female dog, TUR was attempted but not successful because of cystoscope diameter. Iatrogenic urethral perforation occurred during TUR in 3 dogs. In 2 dogs, prolonged exposure to lavage fluid resulted in clinical and biochemical abnormalities consistent with TUR syndrome. Dysuria resolved in 5 dogs within 10 days of TUR. Treatment-related complications included urinary tract infection and tumor seeding. Local tumor progression and metastasis occurred in all dogs. CONCLUSIONS: TUR (in combination with chemotherapy+/-IORT) resulted in rapid palliation of urination difficulties in male dogs with prostatic carcinoma. In female dogs with urethral TCC, however, electrosurgical TUR cannot be recommended because of a high intra- and postoperative complication rate with no improvement in postoperative management compared with historical reports of tube cystostomy. CLINICAL RELEVANCE: TUR is a novel alternative for the palliation of male dogs with prostatic carcinoma. In female dogs with urethral TCC, electrosurgical TUR does not provide any advantages compared with tube cystostomy.

Cyclooxygenase-2 expression in canine appendicular osteosarcomas.

Osteosarcoma is the most common primary bone tumor in dogs and it has a high mortality rate from distant metastatic disease. Targeted adjuvant therapies are needed to prolong currently achievable survival times. The role of cyclooxygenase-2 (COX-2) in carcinogenesis has been attributed to the production of prostaglandins and involvement in apoptosis, immune surveillance, and angiogenesis. COX-2 is up-regulated in a number of different human and animal epithelial tumors, but data about its function in mesenchymal tumors is lacking. The purpose of this study was to evaluate COX-2 expression in canine appendicular osteosarcomas and to identify if a relationship exists between the intensity of COX-2 expression and clinicopathologic outcome. Of 44 osteosarcomas analyzed, 34 (77.3%) were positive for COX-2 expression. Most of the positive cases (88%) had poor to moderate COX-2 staining. Dogs that had strong COX-2 expression had significantly decreased overall survival time (P = .0107). The median survival times for dogs with negative (n = 10), poor (n = 19), moderate (n = 11), and strong (n = 4) expression were 423, 399, 370, and 86 days, respectively. Additional studies are warranted to further evaluate COX-2 in osteosarcoma for its prognostic value and as a target for adjuvant therapy.