Efficacy of mitoxantrone against various neoplasms in dogs

One hundred twenty-six dogs with histologically confirmed, measurable malignant tumors were evaluated in a prospective study to determine the response to the antineoplastic drug mitoxantrone. Ninety-five dogs had been refractory to one or more treatment modalities (surgery, n = 57; chemotherapy other than mitoxantrone, n = 37; radiation, n = 4; whole body hyperthermia, n = 1). The extent of neoplastic disease was determined immediately before each dose of mitoxantrone was administered (1 to 10 doses, 2.5 to 5 mg/m2 of body surface area, IV) 21 days apart. Each dog was treated with mitoxantrone until the dog developed progressive disease or until the dog's quality of life diminished to an unacceptable level as determined by the owner or attending veterinarian. A partial or complete remission (greater than 50% volume reduction) was obtained in 23% (29/126) of all dogs treated. Tumors in which there was a partial or complete remission included lymphoma (11/32), squamous cell carcinoma (4/9), fibrosarcoma (2/9), thyroid carcinoma (1/10), transitional cell carcinoma (1/6), mammary adenocarcinoma (1/6), hepatocellular carcinoma (1/4), renal adenocarcinoma (1/1), rectal carcinoma (1/1), chondrosarcoma (1/2), oral malignant melanoma (1/12), cutaneous malignant melanoma (1/1), myxosarcoma (1/1), mesothelioma (1/1), and hemangiopericytoma (1/1). Our results indicated that mitoxantrone induces measurable regression in various malignant tumors in dogs.     

Investigation of serum survivin in dogs suffering from cancer: a multicenter study

BackgroundIn contrast to human medicine, only a small number of serum tumor markers are established in veterinary medicine even though they are a non-invasive diagnostic tool.ObjectivesThis study examined whether survivin could be suitable as a potential canine serum tumor marker.MethodsThis study measured the serum survivin concentrations of dogs with mammary tumors (n = 33), squamous cell carcinoma (n = 9), soft-tissue sarcoma (n = 18) and multicentric lymphoma (n = 22), using a commercially available, competitive immunoassay kit (BlueGene). The serum survivin concentrations were compared with those of a healthy control group (n = 20) and a control group of dogs with non-neoplastic diseases (n = 17).ResultsDogs with malignant tumors had serum survivin concentrations between 15 and 5,906 pg/mL (median, 72 pg/mL), those in the healthy group ranged from 7 to 99 pg/mL (median, 21 pg/mL) and those in the group of dogs suffering from non-neoplastic diseases from 15 to 93 pg/mL (median, 42 pg/mL). The differences in the survivin concentrations between the healthy dogs and dogs with malignant tumors and between the dogs with non-neoplastic diseases and those with malignant tumors were significant (p < 0.001 and p = 0.006, respectively).ConclusionsThe serum survivin concentrations in dogs with malignant tumors, with some exceptions, are higher than in dogs with benign tumors and dogs that do not suffer from a malignancy. Therefore, survivin can provide information on the presence of malignant tumors and be used as a tumor marker in dogs.     

Weekly administration of low-dose doxorubicin for treatment of malignant lymphoma in dogs

Nine dogs with intermediate- or high-grade lymphoma were prospectively entered into a protocol to be given a total of 15 weekly doses of doxorubicin (10 mg/m2 of body surface, IV) in an attempt to eliminate all clinical evidence of neoplasia, with minimal risk of drug toxicity. Eight of these dogs did not complete the protocol because of progression of the disease. The median number of doses administered to dogs that developed progressive disease before the regimen was completed was 5 (range, 2 to 9). Seven dogs achieved partial (n = 5) or complete (n = 2) remission, with median duration of 14 days (range, 7 to 231 days). The dog that was given all 15 weekly treatments remained in complete remission for 231 days. Complete remission that lasted for 14 days was observed in another dog. Toxicosis developed in 3 dogs; signs of toxicosis were generally mild and included colitis (n = 1), vomiting (n = 1), neutropenia (n = 1), and lethargy (n = 1). The lowest neutrophil count (1,876 cells/microliter) was seen in one dog after 7 doses of doxorubicin were given. Doxorubicin at dosage of 10 mg/m2/wk appears to be safe, but is generally ineffective for treatment of lymphoma.     

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.     

Treatment of Tumor-Bearing Dogs With Actinomycin D

Fifty dogs with advanced malignancies were treated with actinomycin D at doses ranging from 0.5 to 1.1 mg/m² every 3 weeks. The greatest number of responses was noted in dogs with lymphoma, including dogs that had received prior chemotherapy. Other responding tumor types included anal sac adenocarcinoma, perianal adenocarcinoma, squamous cell carcinoma, thyroid carcinoma, and transitional cell carcinoma. The median time to maximum response for dogs with lymphoma was 7 days, with a median duration of 42 days. Gastrointestinal toxicity was the most frequently observed side effect. A dose of 0.6 to 0.7 mg/m² appears to be appropriate for treating various malignancies in dogs.     

Relationship between radiographic evidence of tracheobronchial lymph node enlargement and definitive or presumptive diagnosis

Tracheobronchial lymphadenomegaly is commonly associated with lymphosarcoma and disseminated mycotic infection. Available data also suggest other pathologic causes of enlarged tracheobronchial lymph nodes. Our objective was to establish the distribution and prevalence of diseases that cause radiographically evident tracheobronchial lymphadenomegaly in a large population of dogs. Patients were divided into groups based on the methods of diagnoses with 25 having confirmed diagnoses and 85 with presumptive diagnoses. Of the 110 dogs in the study, 92 (84%) had neoplasia and 18 (16%) had infectious diseases. Infections were attributed to Coccidioides (12, 67%), Aspergillus (3, 17%), and 1 each (6%) to Nocardia, Penicillium, and Mycobacteriosis. Tumors were characterized as lymphoma (66, 60%) or nonlymphoid (26, 23.6%). Nonlymphomas in Group 1 included histiocytic sarcoma complex (16%), carcinoma (12%), adenocarcinoma (8%), osteosarcoma (8%), chemodectoma (4%), ganglioneuroblastoma (4%), and neuroendocrine (4%). The number of dogs with tracheobronchial lymphadenomegaly scores 1, 2, 3, 4, or 5 (with 5 being the greatest) was 8 (7%), 15 (14%), 30 (27%), 15 (14%), and 44 (38%), respectively. The results suggest that in addition to diagnoses of lymphoma and fungal infections, other neoplasms and in particular histiocytic sarcoma and metastatic adenocarcinoma, should be considered when tracheobronchial lymphadenomegaly is identified radiographically in dogs. When comparing the degree of tracheobronchial lymphadenopathy by disease category, there was no significant affiliation (P = 0.33).     

Anti-tumor evaluation of benzaldehyde in the dog and cat

Fourteen dogs and 11 cats with various malignant tumors were treated daily with benzaldehyde at a dosage rate of 10 mg/kg of body weight, orally, divided into 4 doses. Clinical signs of toxicosis were not observed. A partial response (greater than 50% regression) was observed in animals with an oral squamous cell carcinoma and an oral melanoma. A minimal response (less than 50% regression) was observed in animals with a sweat gland adenocarcinoma and a mast cell sarcoma. One dog with an oral melanoma had stabilization of tumor growth for 8 weeks. Seemingly, benzaldehyde has only minimal anti-tumor activity at the dose studied.     

Toxicoses associated with administration of mitoxantrone to dogs with malignant tumors

One hundred twenty-nine dogs with histologically confirmed malignant tumors were used in a prospective study to determine the toxicity of the new dihydroxyquinone derivative of anthracene, mitoxantrone, which was administered IV at 21-day intervals at dosages ranging from 2.5 to 5 mg/m2 body surface area. Each dog was evaluated for signs of toxicosis for 3 weeks after each dose was administered or until the dog died, whichever came first. The number of dogs in each evaluation period were as follows: 1 dose (n = 129), 2 doses (n = 82), 3 doses (n = 43), 4 doses (n = 26), 5 doses (n = 19), 6 doses (n = 9), 7 doses (n = 6), 8 doses (n = 5), 9 doses (n = 3), and 10 doses (n = 1). The most common signs of toxicosis were vomiting, diarrhea, anorexia, and sepsis secondary to myelosuppression. None of the dogs died of complications resulting from mitoxantrone treatment. Dogs with signs of toxicosis during the 21-day interval from administration of the first dose of mitoxantrone were 95 times (P = 0.003) more likely to develop signs of toxicosis during the 21-day interval from the second dose of mitoxantrone. Similarly, dogs that developed signs of toxicosis during the 21-day interval from the administration of the second dose were 34 times (P less than 0.001) more likely to develop signs of toxicosis during the 21-day interval from the administration of the third dose. With each 1 mg/m2 increase in mitoxantrone, the odds of developing signs of toxicosis increased by 5.9 fold (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Peripheral neuropathy associated with malignant neoplasms in dogs

Common peroneal and ulnar nerves of 21 dogs between 2 and 15 years of age with malignant tumors were examined for possible paraneoplastic effects. Percent of abnormalities in single-teased fiber studies exceeded the confidence limits (P = 0.99) established for age-matched control dogs in 16 of 21 dogs (76%) with malignancies, none of which manifested clinical signs of polyneuropathy. The incidence of abnormalities was higher in common peroneal nerve (73%) than in ulnar nerve (57%). Lesions were characterized by a mixture of demyelination/remyelination and axonal degeneration; however, the former lesions predominated in most affected dogs. The severity of the neuropathy varied with different tumors, with the most severe lesions observed in a bronchogenic carcinoma (59%), a mammary adenocarcinoma (59%), a malignant melanoma (48%), and an insulinoma (47%).     

IMAGING FINDINGS IN PANCREATIC NEOPLASIA AND NODULAR HYPERPLASIA IN 19 CATS

Pancreatic neoplasia in cats is rare and associated with a poor prognosis, but pancreatic nodular hyperplasia is a common incidental finding. The purpose of this study was to describe radiographic and ultrasonographic findings in cats with pancreatic neoplasia or nodular hyperplasia. Fourteen cats (age 3-18 years) were diagnosed with malignant pancreatic tumors: carcinoma/adenocarcinoma (n = 11), lymphoma (n = 1), squamous cell carcinoma (n = 1), and lymphangiosarcoma (n = 1). The most common radiographic findings were an abdominal mass or mass effect (6/6) and lack of serosal margin detail (4/6). On ultrasound, the most common finding was a focal pancreatic mass or nodule, with a size range from 0.4 cm to more than 7.0 cm (8/14). Lymphadenopathy (7/14) and abdominal effusion (7/14) were frequently seen. Five cats (age 10-16 years) with adenomatous/nodular hyperplasia had an abdominal mass or mass effect as the most common radiographic finding (3/3). On ultrasound, all cats had multiple hypoechoic nodules between 0.3 and 1.0 cm associated with the pancreas. Other common findings were pancreatic thickening (2/5), lymphadenopathy (2/5), and abdominal effusion (2/5). The only imaging finding unique to malignant pancreatic tumors was the presence of a single pancreatic nodule or mass exceeding 2cm in at least one dimension (4/14). Although there was a tendency for neoplastic lesions to manifest as single larger lesions and for nodular hyperplasia to manifest as multiple smaller lesions, there was overlap of the imaging findings in both entities. Radiographs and ultrasound can complement but not replace cytology and histopathology in the diagnosis of feline pancreatic neoplasia.     

RADIOGRAPHIC CHARACTERIZATION OF PRIMARY LUNG TUMORS IN 74 DOGS

Primary pulmonary neoplasia is well recognized in dogs and prognosis depends upon the tumor type. The purpose of this retrospective study was to characterize the radiographic appearance of different primary lung tumors with the goal of establishing imaging criteria to separate the different types. Three‐view thoracic radiographs of 74 dogs with histologically confirmed pulmonary anaplastic carcinoma (n = 2), adenocarcinoma (n = 31), bronchioalveolar carcinoma (n = 19), histiocytic sarcoma (n = 21), and squamous cell carcinoma (n = 1) were evaluated. Radiographs were assessed for tumor volume, affected lobe, location within lobe, overall pulmonary pattern, presence of cavitation, mineralization, air bronchograms, lymphadenomegaly, and pleural fluid. Histiocytic sarcomas were significantly larger than other tumor types (271 cm³; P = 0.009) and most likely to be found in the left cranial (38%; 8/21) and right middle (43%; 9/21) lung lobes, whereas adenocarcinomas were most likely to be found in the left caudal (29%; 9/31) lung lobe. Fifty‐seven percent (12/21) of histiocytic sarcomas had an internal air bronchogram. Findings indicate that a large mass in the periphery or affecting the whole lobe of the right middle or left cranial lung lobe with an internal air bronchogram is likely to be an histiocytic sarcoma.     

Evaluation of ifosfamide for treatment of various canine neoplasms

lfosfamide (3-[2-chloroethyl]-2[(2 chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty-two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide postsplenectomy and their median survival time was 147 days. The acute dose limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor-bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.     

A clinicopathologic and ultrastructural study of undifferentiated malignant tumors of the oral cavity in dogs

Undifferentiated malignant tumors of the oral cavity were diagnosed in six dogs under 2 years of age. The dogs were examined because of pain and swelling of the upper molar or premolar areas. In all six dogs, the tumors were initially misdiagnosed as infections or carnasal abscesses. The differential diagnosis included malignant lymphoma, osteosarcoma, mesenchymal chondrosarcoma, embryonal rhabdomyosarcoma, and malignant melanoma. Electron microscopy of three neoplasms showed that there were no specific features characteristic of carcinoma or sarcoma. Immunoperoxidase studies for cytokeratins, epithelial membrane antigen, actin, myosin, desmin, and vimentin were also negative. We conclude that these tumors be designated undifferentiated malignant tumors of the oral cavity until histogenesis is established.     

Hyperlipasemia in 6 dogs with pancreatic or hepatic neoplasia: evidence for tumor lipase production

Abstract: A marked increase in serum pancreatic lipase (PL) activity with minimal concurrent increase in serum α-amylase activity was observed in 6 dogs with pancreatic or hepatic neoplasia. Serum PL activity ranged from 5410 U/L to 42,900 U/L, 11 to 93 times the upper reference limit for our laboratory. Neoplasms included pancreatic adenocarcinoma (n=3), endocrine carcinoma (n=2), and hepatic carcinoma of unknown origin (n=1). Tumor tissue and normal canine pancreatic tissue were stained histochemically with diastase periodic acid-Schiff to demonstrate zymogen granule content, and immunohistochemically with human monoclonal antibody for PL. Normal canine pancreatic tissue stained positive for both zymogen granule content and PL. Five of the 6 tumors stained positive for zymogen granule content, and 2 of the 6 tumors stained positive for PL. Together, the his-tochemical and immunohistochemical staining patterns suggested tumor PL production in 5 of the 6 dogs. Marked, unexplained hyperlipasemia may be a noninvasive indicator and biochemical marker for neoplasia of the pancreas and liver in dogs.     

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   

Radiotherapy of malignant nasal tumors in 67 dogs

The nasal cavity of 67 dogs with malignant nasal neoplasia was treated with radiation. Preirradiation surgical cytoreduction of the tumor was done in 41 dogs. Fifty dogs were irradiated by use of 10 fractions over 22 days, and 17 dogs were given a similar total dose in 5 fractions over 35 days. The range of survival times (0.5 to 42 months), median survival time (8.5 months), and 1- and 2-year survival rates (38% and 30%, respectively) were better than those expected for other methods of treatment. Serious complications were few (4%). Survival times for dogs were determined on the basis of histologic tumor type and on the basis of megavoltage (cobalt or linear accelerator) vs softer deep radiation (cesium or orthovoltage) treatment, with or without cytoreductive surgery. Survival times of 10 dogs given softer radiation without surgery were shorter than those of 14 dogs that were given softer radiation and had cytoreductive surgery. Survival times of dogs that were given softer radiation and had surgery were similar to those of dogs that were given megavoltage radiation only. Cytoreductive surgery did not improve survival times for dogs that were given megavoltage radiation. Median survival time for 38 dogs with adenocarcinoma was 12 months, compared with 6 months for 14 dogs with squamous cell or undifferentiated carcinoma. Median survival time for 16 dogs with a variety of sarcomas was 11.2 months. Survival times of dogs with adenocarcinoma or sarcoma were significantly better (P less than 0.02 or 0.03) than for dogs with squamous cell or undifferentiated carcinoma. Necropsies were performed on 27 of 58 dogs that died or were euthanatized.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognostic significance of clinical presentation,induction and rescue treatment in 42 cases of canine centroblastic diffuse large B‐cell multicentric lymphoma in the United Kingdom

Canine lymphoma is a heterogeneous group of diseases and many previous studies have evaluated the response of a mixed population of lymphoma cases to one specific treatment protocol. The aim of this retrospective study was to describe the outcome and prognostic factors in 42 cases of multicentric centroblastic diffuse large B‐cell lymphoma treated with either a COP‐type (35%) or CHOP‐type (64%) induction chemotherapy. The objective response rate to induction therapy was 94%; entire dogs had a greater rate of complete vs partial remissions than neutered dogs (P = .017). Median progression‐free survival for the first remission (PFS1) was 182 days; absence of anaemia at diagnosis (P = .002) and pretreatment neutrophil:lymphocyte ratio (NLR) below 9.44 (P = .015) were independently predictive of longer PFS1. Fifty‐eight percent of dogs received rescue protocols with an objective response rate of 81%; 31% of dogs received further rescue protocols (up to a total of 5) and the median number of protocols administered were 2. Median overall survival (OS) was 322 days, the 1‐year survival rate was 38% and the 2‐year survival rate was 9%. Lymphocyte:monocyte ratio above 1.43 (P = .031), NLR below 11.44 (P = .009), the combination of induction and rescue therapy (P = .030) and the total number of doxorubicin doses used (P = .002) were independently predictive of longer OS. Use of a COP‐type protocol induction compared with CHOP did not undermine OS providing doxorubicin was used as rescue therapy.     

Postoperative adjuvant treatment of invasive malignant mammary gland tumors in dogs with doxorubicin and docetaxel

BACKGROUND: Treatment outcome after surgery alone is unsatisfactory in dogs with invasive malignant mammary gland tumors. HYPOTHESIS: Adjuvant doxorubicin or docetaxel will improve the treatment outcome in dogs with high-risk malignant mammary gland tumors, and the use of docetaxel will be feasible in affected dogs. ANIMALS: Thirty-one dogs with malignant mammary gland tumors of histologic stages II and III (vascular or lymphatic invasion, regional lymph node metastasis, or distant metastasis) were used. METHODS: A prospective clinical trial in which dogs were treated with surgery alone (n = 19) or also received adjuvant chemotherapy (n = 12) with doxorubicin or docetaxel was conducted. Docetaxel was given as an IV infusion at a dose of 30 mg/m2 preceded by dexamethasone and diphenhydramine administration. RESULTS: The recurrence-free interval ranged from 13 to 2,585 days (median not reached); the median metastasis-free interval and overall survival were 294 days and 370 days, respectively. Dogs treated with chemotherapy had a tendency toward higher long-term local control and survival rates, but there was no significant difference in the recurrence-free interval (P = .17), time to metastasis (P = .71), and overall survival (P = .12). Factors found to influence the time to metastasis and overall survival included lymph node metastasis (P = .009) and tumor fixation to underlying structures (P = .043, time to metastasis), as well as age (P = .018) and histologic stage (P < .001, survival). Mild allergic skin reactions were the most frequently observed complications of docetaxel treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Chemotherapy did not lead to an improved outcome in this population. Docetaxel treatment was well tolerated. Additional investigations of adjuvant chemotherapy in dogs with high-risk mammary cancer are warranted.     

Prevalence of nephrotoxicosis associated with a short-term saline solution diuresis protocol for the administration of cisplatin to dogs with malignant tumors: 61 cases (1987-1989).

The study reported here was undertaken to determine the nephrotoxicosis associated with the administration of cisplatin, an antineoplastic agent, to dogs when administered during 6-hour saline solution diuresis. Cisplatin (70 mg/m2 of body surface, IV, every 21 days) was given to 61 dogs with malignant neoplasia with a total of 185 doses in 1 (n = 9 dogs), 2 (n = 26 dogs), 3 (n = 4 dogs), 4 (n = 9 dogs), 5 (n = 2 dogs), and 6 (n = 11 dogs) treatments. The cisplatin was given over a 20-minute period after 0.9% NaCl solution (saline solution) was administered IV for 4 hours at a rate of 18.3 ml/kg of body weight/h. After the cisplatin infusion, saline solution diuresis was continued at the same rate for 2 hours. Before each treatment with cisplatin, dogs were evaluated with at least a physical examination, CBC, determination of serum urea nitrogen concentration, and in most cases, determination of serum creatinine concentration and urine specific gravity. Four of the 61 dogs (6.6%) developed clinically evident renal disease after 2 (1 dog), 3 (2 dogs), and 4 (1 dog) doses of cisplatin were administered. Three of the 4 dogs had preexisting disease of the urinary tract prior to the start of treatment. The survival time in dogs that developed renal disease (median, 145 days; range, 15 to 150 days) was similar to that of all dogs in this study (median, 154 days; range, 30 to 500 days), with 13 dogs still alive at the conclusion of the study.(ABSTRACT TRUNCATED AT 250 WORDS)