CCNU in the treatment of canine epitheliotropic lymphoma

This retrospective study examined the use of CCNU (1-[2-chloroethyl]3-cyclohexyl-1-nitrosurea) in 36 dogs with epitheliotropic lymphoma. Thirty-one (86%) dogs had the cutaneous form of disease, and 5 (14%) dogs had the oral form of disease. Nineteen (51%) dogs were treated with other chemotherapeutic agents before receiving CCNU. All dogs had detectable disease at the time CCNU therapy was initiated. Dogs received a median starting CCNU dosage of 70 mg/m2 (range, 50-100 mg/m2). The median number of treatments administered was 3 (range, 1-12 treatments). After the initial treatment, the CCNU dosage was adjusted in 9 of 26 (35%) dogs in which CCNU was continued: 7 had dosage reductions, and 2 had dosage escalations. Twenty-eight of 36 (78%) dogs had a measurable response to CCNU for a median duration of 106 days (95% confidence interval [CI], 75-182). Six dogs (17%) had a complete response, including 5 dogs with the cutaneous form and 1 dog with the oral form. Twenty-two dogs (61%) had a partial response, including 20 dogs with the cutaneous form and 2 dogs with the oral form, for a median duration of 88 days (95% CI, 62-170). Toxicoses after CCNU chemotherapy included myelosuppression in up to 29% of the dogs, gastrointestinal signs in up to 22% of the dogs, and liver enzyme activity increases in up to 86% of the dogs. This study demonstrates that CCNU chemotherapy can be considered a reasonable option for the treatment of canine epitheliotropic lymphoma in dogs.     

Risk factors for sterile hemorrhagic cystitis in dogs with lymphoma receiving cyclophosphamide with or without concurrent administration of furosemide: 216 cases (1990-1996)

OBJECTIVES: To determine incidence and identify predisposing factors for sterile hemorrhagic cystitis (SHC) in dogs with lymphoma that were treated with cyclophosphamide and to evaluate whether furosemide administered i.v. concurrently with cyclophosphamide decreased the incidence of SHC. DESIGN: Retrospective study. ANIMALS: 216 dogs with lymphoma. PROCEDURE: Medical records of dogs with lymphoma that received cyclophosphamide chemotherapy in accordance with 1 of 2 protocols, with or without concurrent i.v. administration of furosemide, were examined. Data for the 2 groups were analyzed to determine the incidence and predisposing factors (age, breed, sex, weight, previous or preexisting disease, previous or preexisting urinary tract infection, neutropenia, azotemia, dose, and number of cyclophosphamide treatments) for cyclophosphamide-associated SHC. RESULTS: Cyclophosphamide-associated SHC developed in 12 of 133 (9%) dogs that had not received concurrent administration of furosemide and cyclophosphamide treatments; of the 83 dogs that had received furosemide, only 1 (1.2%) developed SHC. Dogs receiving cyclophosphamide and furosemide concurrently were significantly less likely to develop SHC than dogs that did not receive furosemide. Dogs with previous or preexisting immune-mediated disease were significantly more likely to develop cyclophosphamide-associated SHC. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results suggested an association between i.v. administration of furosemide concurrently with cyclophosphamide and decreased incidence of cyclophosphamide-associated SHC. Incidence of cyclophosphamide-associated SHC was similar in treated dogs that did not receive concurrent furosemide to that observed for other studies in which cyclophosphamide was administered orally. Cyclophosphamide-associated SHC appeared to develop early during the course of chemotherapy when furosemide was not administered concurrently with cyclophosphamide.     

Serum liver enzyme activities in healthy Miniature Schnauzers with and without hypertriglyceridemia

OBJECTIVE: To determine whether hypertriglyceridemia in healthy Miniature Schnauzers is associated with high serum liver enzyme activities. DESIGN: Cross-sectional study. ANIMALS: 65 Miniature Schnauzers with serum triglyceride concentrations within the reference range (group 1), 20 Miniature Schnauzers with slightly high serum triglyceride concentrations (group 2), and 20 Miniature Schnauzers with moderately to severely high serum triglyceride concentrations (group 3). PROCEDURES: Questionnaires regarding each dog's medical history were completed, and serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and G-glutamyltransferase (GGT) activities were measured. RESULTS: Median serum ALP activity was significantly higher in group 3 than in group 1 or 2 dogs, but was not significantly higher in group 2 than in group 1 dogs. Median serum ALT activity was significantly higher in group 3 than in group 1 dogs, but was not significantly different between any of the other groups. Compared with group 1 dogs, group 2 and 3 dogs were significantly more likely to have high serum ALP activity (odds ratio, 26.2 and 192.6, respectively). Group 3 dogs also were significantly more likely to have high serum ALT activity (odds ratio, 8.0), serum AST activity (odds ratio, 3.7), and serum GGT activity (odds ratio, 11.3), compared with group 1 dogs. Group 3 dogs were significantly more likely (odds ratio, 31.0) to have > or = 2 high serum liver enzyme activities than were group 1 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that moderate to severe hypertriglyceridemia was associated with high serum liver enzyme activities in Miniature Schnauzers.     

Increased Serum Alanine Aminotransferase Activity Associated With Muscle Necrosis in the Dog

Serum activity of alanine aminotransferase (ALT) was consistently increased in dogs with canine X-linked muscular dystrophy (CXMD), a primary myopathy characterized by profound and on-going skeletal muscle necrosis. In order to determine whether the ALT was of liver origin, serum activity of creatine kinase (CK), aspartate aminotransferase (AST), ALT, and sorbitol dehydrogenase (SDH) obtained from dystrophic dogs was compared with enzyme activity present in clinically normal dogs. In dystrophic dogs at all ages tested, serum activity of CK, AST, and ALT was increased, and significant increases were present in dogs four weeks or older. In contrast, SDH activity in dystrophic dogs was not statistically different from values in clinically normal dogs. Ultrastructural examination of liver tissue revealed no evidence of hepatic degeneration in dystrophic dogs. It was concluded that increased serum activity of ALT in the dog may be associated with severe skeletal muscle degeneration, without concurrent hepatocellular necrosis.     

Prevalence of elevated alanine transaminase activity in dogs treated with CCNU (Lomustine)*

The purpose of this study was to evaluate prevalence of serum alanine transaminase (ALT) elevation in dogs receiving lomustine (CCNU) and to analyse the pattern of occurrence and potential risk factors. Serum ALT activity in 109 dogs during single‐agent CCNU chemotherapy was retrospectively analysed. The median initial dose, dose‐intensity and cumulative dose of CCNU were 64 mg m^?2, 21 mg m^?2 week^?1 and 171 mg m^?2, respectively. The overall prevalence of major ALT elevation [> 5‐fold upper reference limit (URL)] was 29% (32/109) and developed most commonly after one to three doses of CCNU. These ALT elevations occurred without preceding mild ALT elevation in 53% (17/32) of the cases. Three dogs (2.8%) developed clinical hepatopathy. For severe ALT elevation (>10‐fold URL), age ≤5‐year‐old was associated with higher risk. The findings of this study showed that elevation of ALT is common during CCNU chemotherapy in dogs and severe elevation can develop on a sudden onset.     

Carboplatin versus alternating carboplatin and doxorubicin for the adjuvant treatment of canine appendicular osteosarcoma: a randomized,phase III trial

Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease‐free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin.     

Evaluation of adverse effects of long-term orally administered carprofen in dogs

OBJECTIVE: To evaluate the adverse effects of carprofen in dogs after oral administration for 2 months. DESIGN: Prospective, randomized, blinded, placebo-controlled clinical trial. ANIMALS: 22 dogs with osteoarthritis in the hip or elbow joint. PROCEDURE: 13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, gamma-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects. RESULTS: Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group. CONCLUSIONS AND CLINICAL RELEVANCE: It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.     

Comparison of 3 protocols for treatment after induction of remission in dogs with lymphoma

BACKGROUND: The optimal treatment after inducing complete remission (CR) in dogs with lymphoma has not been established. HYPOTHESIS: After inducing CR with L-asparaginase, vincristine, cyclophosphamide, doxorubicin, prednisone (L-CHOP); consolidation with either half-body radiation therapy (HBRT); or lomustine (CCNU) and mechlorethamine, vincristine, procarbazine, prednisone (MOPP) would improve first remission duration compared with continuing a CHOP-based protocol for an additional 4 months. ANIMALS: Dogs with stage III-V lymphoma. METHODS: Prospective clinical trial in which dogs initially were treated with an 8-week induction protocol that consisted of L-CHOP. Dogs in CR after induction were then allocated to 1 of 2 consolidation arms. A chemotherapy consolidation arm consisted of 2 treatments with CCNU and 1 cycle of MOPP. A HBRT arm consisted of 2 sequential 8.0-Gy fractions to the cranial and caudal half-body separated by 30 days. Vincristine was given between fractions. Results of the consolidation arms also were compared with a historical group treated with the same 8-week induction protocol followed by CHOP therapy until week 24. RESULTS: Overall, 67% of the dogs were in CR after 8 weeks of induction chemotherapy and were compared. Fifty-two dogs were in the historical arm, 23 in the CCNU/MOPP arm, and 27 in the HBRT arm. No difference in first remission duration was found among groups. Median first remission duration for the historical, CCNU/MOPP, and HBRT arms were 307, 274, and 209 days, respectively (P = .28). Overall second CR rate was 82% and was not different among groups (all P > or = .58). Overall remission duration (P = .28) and survival time (P = .48) were not different among groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Consolidation with either CCNU/MOPP or HBRT showed no advantage over a standard CHOP-based protocol.     

Liver histopathology and liver and serum alanine aminotransferase and alkaline phosphatase activities in epileptic dogs receiving phenobarbital

Phenobarbital (PB) therapy is frequently associated with elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (AP) activities in dogs without clinical signs of liver disease. The goal of this study was to determine if increased serum ALT and AP activities in clinically healthy PB-treated epileptic dogs are due to hepatic enzyme induction or to subclinical liver injury. Liver biopsies were obtained from 12 PB-treated dogs without clinical signs of liver disease but with elevated serum ALT and/or AP activities or both. Liver biopsies were obtained from eight healthy control dogs not receiving PB. Biopsies were evaluated histopathologically (all dogs) and liver homogenates were assayed for ALT (all dogs) and AP (six treated dogs, all controls) activities. As a positive control, liver cytochrome P4502B, an enzyme known to be induced by PB, was measured by benzyloxyresorufin-O-dealkylase activity and immunoblotting (five treated dogs, all controls). Serum AP isoenzyme analyses were performed. Results showed that ALT and AP activities in liver homogenates were not increased in treated dogs compared with controls, whereas the positive control for induction, CYP2B, was dramatically increased in treated dogs. Histopathological examination of liver biopsies revealed more severe and frequent abnormalities in treated dogs compared to controls, but similar types of abnormalities were found in both groups. Serum AP isoenzyme analyses in treated dogs demonstrated increased corticosteroid-induced and liver isoenzyme activities compared to controls. Results do not support induction of ALT or AP in the liver as the cause of elevated serum activities of these enzymes due to PB.     

Survival times in dogs with right atrial hemangiosarcoma treated by means of surgical resection with or without adjuvant chemotherapy: 23 cases (1986-2000)

OBJECTIVE: To determine survival times in dogs with right atrial hemangiosarcoma treated by means of pericardectomy and tumor resection, with or without adjuvant chemotherapy, and identify complications associated with treatment. DESIGN: Retrospective study. ANIMALS: 23 dogs. PROCEDURE: Dogs were included only if the diagnosis was confirmed histologically. RESULTS: The most common initial complaints included acute collapse (8 [35%] dogs), anorexia or inappetence (8 [35%]), and lethargy (8 [35%]). The most common physical examination abnormalities included muffled heart sounds (12 [52%] dogs), tachycardia (7 [30%]), and weak pulses (7 [30%]). Postoperative complications developed in 12 (52%) dogs; however, most complications were minor. Twenty (87%) dogs were discharged from the hospital. Survival time was significantly longer in the 8 dogs that received adjuvant chemotherapy (mean, 164 days; median, 175 days) than in the 15 dogs that did not receive chemotherapy (mean, 46 days; median, 42 days). Dogs that received chemotherapy were significantly younger and had significantly lower WBC counts than did dogs that did not receive chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that in dogs with right atrial hemangiosarcoma, surgical resection of the tumor was associated with a low complication rate and complications that did arise typically were minor. In addition, use of adjuvant chemotherapy following resection was associated with significantly longer survival times, compared with resection alone.     

Clinical Efficacy of Sildenafil in Treatment of Pulmonary Arterial Hypertension in Dogs

Background: Pulmonary arterial hypertension (PAH) in dogs carries a poor prognosis. Sildenafil increases exercise capacity and improves hemodynamics in people with PAH. Hypothesis/Objectives: Dogs receiving sildenafil will have lower pulmonary arterial pressure, increased exercise capacity, and better quality of life (QOL) than dogs receiving placebo. Animals: Thirteen dogs with echocardiographic evidence of PAH. Methods: Prospective short‐term, randomized, placebo controlled, double‐blind, crossover study. Dogs with PAH were randomly allocated to receive sildenafil or placebo for 4 weeks, followed by the alternative treatment for 4 weeks. Results: Dogs receiving sildenafil had a significantly lower estimated pulmonary arterial pressure (median, 56 mmHg; range, 34–83 mmHg) than at baseline (median, 72 mmHg; range, 61–86 mmHg; P= .018), but not significantly lower than those receiving placebo (median, 62 mmHg; range, 49–197 mmHg). Exercise capacity was significantly greater in dogs receiving sildenafil than those receiving placebo (mean activity count per minute: 101 ± 47 versus 74 ± 32; P= .05). QOL scores were significantly higher in dogs receiving sildenafil than dogs receiving placebo. Conclusions and Clinical Importance: Sildenafil decreases systolic pulmonary arterial pressure from baseline in dogs with PAH and is associated with increased exercise capacity and QOL when compared to treatment with placebo.     

The effect of otic vehicle and concentration of dexamethasone on liver enzyme activities and adrenal function in small breed healthy dogs

Dexamethasone 0.1% in propylene glycol vehicle has been shown to cause adrenal suppression and increased liver enzyme concentrations in normal dogs. The objectives of this study were to determine if these effects are concentration or vehicle dependent and to evaluate a dexamethasone 0.01% solution. Twenty-one privately owned normal dogs were included in this double-blinded study. Chemistry panels and adrenocorticotropin hormone (ACTH) stimulation tests were performed on day 0 and 15. Dogs were randomly assigned treatment with dexamethasone 0.01% in saline, 0.1% in saline, or 0.1% in a commercial preparation (Tresaderm®: Merial, Duluth, GA, USA) in each ear twice daily for 2 weeks. Nineteen dogs completed the study. After 2 weeks of treatment, all dogs receiving dexamethasone 0.01% in saline had normal ACTH stimulation tests and liver enzyme values. In contrast, four of seven dogs (57.14%) receiving dexamethasone 0.1% in saline experienced adrenal suppression, and four of six dogs (66.67%) receiving Tresaderm® experienced adrenal suppression with three of those dogs (50%) experiencing marked adrenal suppression. No dogs receiving dexamethasone 0.1% in saline had increased liver enzyme concentration, while one of six dogs (16.67%) experienced a slight elevation in alkaline phosphatase. In conclusion, it appears that adrenal suppression caused by otic dexamethasone is concentration and perhaps vehicle dependent. Veterinarians who formulate dexamethasone 0.1% otic solutions should be cognizant of potential adrenal suppression similar to that seen with Tresaderm® although not to the same degree. Dexamethasone at 0.01% did not cause adrenal suppression or liver enzyme alterations after 2 weeks of treatment.     

Hepatotoxicity associated with CCNU (lomustine) chemotherapy in dogs

One hundred seventy-nine tumor-bearing dogs were treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) between 1995 and 2001. CCNU was given as a single dose of 50-110 mg/m2 body surface area PO. Treatment interval varied, but the minimal interval between CCNU doses was 3 weeks. After treatment, 11 dogs (6.1%) developed hepatic toxicity. The median number of CCNU doses and the median total cumulative CCNU dose were significantly higher in dogs that developed hepatic toxicity (4 doses; 350 mg/m2) than in dogs without hepatic damage (3 doses; 230 mg/m2). Median duration to detection of hepatic toxicity from the last dose of CCNU was 11 weeks (range 2-49 weeks). Common biochemical abnormalities were abnormally high serum liver enzyme activities and hypoalbuminemia. Six dogs with CCNU-associated hepatic toxicity had ascites, and 3 dogs had concurrent pleural effusion. Serum concentrations of bile acids were abnormally high in 4 of 5 dogs tested. Percutaneous ultrasound-guided liver biopsies were performed in 10 dogs, and findings were nonspecific and chronic in nature. Seven dogs were euthanized because of progressive liver failure, and their median survival from diagnosis of liver disease was 9 weeks. Three dogs died of other causes and 1 dog of unknown cause. Although clinical signs resolved in 3 dogs, biochemical abnormalities and histopathologic lesions persisted 4 to 38 months from the time of diagnosis of liver disease. Our findings suggest that CCNU can cause delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and can be fatal.     

Carcinoma of the apocrine glands of the anal sac in dogs: 113 cases (1985-1995)

OBJECTIVE: To characterize the signalment, clinical signs, biological behavior, and response to treatment of carcinoma of the apocrine glands of the anal sac in dogs. DESIGN: Retrospective study. ANIMALS: 113 dogs with histologically confirmed carcinoma of the apocrine glands of the anal sac. PROCEDURE: Data on signalment, clinical signs, and staging were reviewed and analyzed along with treatment modality for potential association with survival time. RESULTS: Sex distribution was approximately equal (54% female, 46% male). One hundred four dogs underwent treatment consisting of surgery, radiation therapy, chemotherapy, or multimodal treatment. Median survival for treated dogs was 544 days (range, 0 to 1,873 days). Dogs treated with chemotherapy alone had significantly shorter survival (median, 212 days) than those receiving other treatments (median, 584 days). Dogs not treated with surgery had significantly shorter survival (median, 402 days) than those that underwent surgery as part of their treatment (median, 548 days). Dogs with tumors > or = 10 cm2 had significantly shorter survival (median, 292 days) than dogs with tumors < 10 cm2 (median, 584 days). Hypercalcemia was identified in 27% (n = 29) of dogs, and those dogs had significantly shorter survival (median, 256 days), compared with those that were normocalcemic (median, 584 days). Dogs with pulmonary metastasis had significantly shorter survival (median, 219 days) than dogs without evidence of pulmonary metastasis (median, 548 days). CONCLUSIONS AND CLINICAL RELEVANCE: Unlike most previous reports, this study revealed an approximately equal sex distribution, and results suggest a more favorable prognosis.     

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.     

Influence of halothane, isoflurane, and sevoflurane on gastroesophageal reflux during anesthesia in dogs

OBJECTIVE: To determine whether maintenance of anesthesia with halothane or sevoflurane is associated with a lower incidence of gastroesophageal reflux (GER) than the use of isoflurane in dogs undergoing orthopedic surgery. ANIMALS: 90 dogs. PROCEDURES: Dogs were evaluated during elective orthopedic surgery. Dogs with a history of vomiting or that had received any drugs that would alter gastrointestinal tract function were excluded from the study. The anesthetic protocol used was standardized to include administration of acepromazine maleate and morphine prior to induction of anesthesia with thiopental. Dogs were allocated to receive halothane, isoflurane, or sevoflurane to maintain anesthesia. A sensor-tipped catheter was placed to measure esophageal pH during anesthesia. Gastroesophageal reflux was defined as an esophageal pH < 4 or > 7.5. RESULTS: 51 dogs had 1 or more episodes of acidic GER during anesthesia. Reflux was detected in 14 dogs receiving isoflurane, 19 dogs receiving halothane, and 18 dogs receiving sevoflurane. In dogs with GER, mean +/- SD time from probe placement to onset of GER was 36 +/- 65 minutes and esophageal pH remained < 4 for a mean of 64% of the measurement period. There was no significant association between GER and start of surgery or moving a dog on or off the surgery table. Dogs that developed GER soon after induction of anesthesia were more likely to regurgitate. CONCLUSIONS AND CLINICAL RELEVANCE: Maintenance of anesthesia with any of the 3 commonly used inhalant agents is associated with a similar risk for development of GER in dogs.     

Histiocytic sarcomas in flat-coated retrievers: a summary of 37 cases (November 1998–March 2005)

Thirty‐seven cases of histiocytic‐like sarcomas (HLSs) in flat‐coated retriever dogs were evaluated retrospectively. This tumour accounted for 36% of the malignant tumours seen in this breed during the study period. The median age at presentation was 8.2 years. Thirty‐four dogs presented with a swelling or mass in a muscle group or surrounding a joint. The remaining three presented for rib (1), cutaneous (1) or primary splenic origin (1). A high rate of metastasis to local lymph nodes (45%), thorax (20%) and abdominal organs (20% confirmed) was seen. Overall metastastic rate by the time of death was 70%. The median survival for all dogs was 123 days. The most significant prognostic indicator was presence of distant metastasis at the time of diagnosis with median survival of 68 or 200 days, with or without metastasis, respectively. Chemotherapy and radiation therapy significantly improved survival. Dogs given chemotherapy survived a median of 185 versus 34 days for dogs that were not (P = 0.0008). Dogs treated with radiation survived a median of 182 versus 60 days for those that were not (P = 0.0282). Dogs receiving only palliative therapy survived a median of 17 versus 167 days in dogs receiving any kind of radiation, chemotherapy, surgery or combinations. A set protocol of radiation and CCNU (RTCCNU) induced minimal toxicity and provided a median survival of 208 versus 68 days for all other dogs. While this tumour carries a poor long‐term prognosis in flat‐coated retrievers, it is reasonable to treat these dogs for palliation of signs and extension of life.     

CORRELATION OF ULTRASOUND FINDINGS,LIVER AND SPLEEN CYTOLOGY,AND PROGNOSIS IN THE CLINICAL STAGING OF HIGH METASTATIC RISK CANINE MAST CELL TUMORS

Cytologic sampling of the ultrasonographically normal spleen and liver is not implemented routinely in the clinical staging of canine cutaneous mast cell tumors and normal ultrasound findings are often accepted as sufficient evidence for ruling out splenic or liver metastasis. Our objective was to define the specificity and sensitivity of ultrasound findings for diagnosis of mast cell infiltration when verified with cytologic evaluation, and to define the prognostic role of cytologic evaluation of liver and splenic aspirates. Dogs with a diagnosis of clinically aggressive grade II, or grade III mast cell tumor treated with a combination vinblastine/CCNU chemotherapy protocol, were selected retrospectively based on availability of cytologic evaluation of spleen plus or minus liver for staging. Out of 19 dogs, 10 dogs had a grade II tumor and nine a grade III tumor. Seven dogs had mast cell infiltration of the spleen, liver, or both. The sensitivity of ultrasound for detecting mast cell infiltration was 43% for the spleen and 0% for the liver. Dogs with positive cytologic evidence of mast cell infiltration to spleen, liver, or both had significantly shorter survival (100 vs. 291 days) than dogs without evidence of mast cell infiltration (P<0.0001). Routine splenic aspiration should be performed regardless of ultrasonographic appearance in dogs with a clinically aggressive mast cell tumor.     

Lomustine (CCNU) for the Treatment of Resistant Lymphoma in Dogs

Forty-three dogs with lymphoma that had relapsed or had failed to achieve complete remission to previous chemotherapy were treated with lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea [CCNU]) at a dosage of 90-100 mg/m2 body surface area p.o. every 3 weeks. Durable complete or partial responses occurred in 11 dogs for a median of 86 days. The acutely dose-limiting toxicosis was neutropenia 7 days after administration, resulting in a recommended dosage of 90 mg/m2. Cumulative thrombocytopenia occurred in dogs receiving continued CCNU treatment, and a dose interval of 3 weeks may be too short for continued administration of this drug. Toxicoses evident as fever or central nervous system signs or renal damage were uncommon or rare. CCNU is effective in the treatment of relapsed lymphoma.     

Cisplatin and doxorubicin toxicosis in dogs with osteosarcoma

Toxicosis associated with doxorubicin and cisplatin administration starting either 2 or 10 days after limb amputation for osteosarcoma was examined retrospectively in dogs. The purpose was to determine whether dosage and timing of chemotherapy affected rates of toxicosis after administration of the 1st treatment. Records of 100 dogs with appendicular osteosarcoma without evidence of metastases or concurrent disease were examined. Dogs received chemotherapy with doxorubicin and cisplatin every 3 weeks for 3 treatments starting 2 days (n = 51) or 10 days (n = 49) after amputation. The dosage of cisplatin was 60 mg/m2 and was given with 6-hour saline diuresis and butorphanol. Doxorubicin was given at 12.5-25 mg/ml during fluid administration. Hematologic data were collected before and weekly after treatment. Client interviews were conducted to assess gastrointestinal toxicosis during the interval between treatments. The reported toxicoses were graded on a scale of 0 to 4. Dogs receiving 25 mg/m2 of doxorubicin experienced greater rates of grade 4 toxicity (67%; n = 6) than dogs in groups receiving 12.5-20 mg/m2 of doxorubicin (< or = 25%; n = 94, P = .03). Dogs in the Day 2 group experienced greater rates (35%) of grade 4 toxicity than dogs in the Day 10 group (12%, P = .007). We concluded that chemotherapy administered 2 days after surgery produced an unacceptable level of toxicoses. except at greatly reduced dosages, and that even with a delay of treatment, 25 mg/m2 of doxorubicin, when given in combination with cisplatin at 60 mg/m2, was too toxic for routine use.