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BACKGROUND: While rare, multiple individual case reports have described mixed thyroid tumours in dogs containing both epithelial and mesenchymal neoplastic components. OBJECTIVES: In this retrospective case series, we describe the clinical presentation, treatment and outcome of 14 dogs of canine thyroid tumours with concurrent mesenchymal and epithelial neoplastic populations. METHODS: Fourteen cases were retrospectively abstracted from nine institutions. Histopathologic samples and reports were collected from 10/14 dogs and reviewed by a single board-certified anatomic pathologist. RESULTS: All 14 dogs had curative-intent surgery to remove the thyroid neoplasm. The most common surgery performed was a unilateral thyroidectomy (10/14 dogs). Postoperatively, systemic therapy was administered in eight dogs. Six dogs developed local recurrence with a median time to loco-regional recurrence of 53 days. Ten dogs developed metastatic disease with the most common metastatic site being the lungs (6/10 dogs), with a median time to metastasis of 93 days. Ten dogs were euthanised due to locoregional or distant progression of their mixed thyroid neoplasm. The overall median survival time was 156 days (95%CI: 49-244). The median survival time for dogs treated with adjuvant therapy was 189 days (95%CI: 24-244), whereas dogs without adjuvant therapy had a median survival time of 156 days (95%CI: 35-upper limit could not be calculated; p = 0.62). CONCLUSION: The thyroid tumours with both mesenchymal and epithelial components in this small sample set were associated with a poor prognosis after surgical excision with or without adjunctive therapy.

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BACKGROUND: Despite multiple reports of chemotherapy overdoses (ODs) in human and veterinary medicine, anthracycline ODs have been described infrequently. HYPOTHESIS/OBJECTIVES: Describe toxicities, treatments, and overall outcome after anthracycline OD in dogs. ANIMALS: Twelve mitoxantrone (MTX) and 4 doxorubicin (DOX) ODs were evaluated. METHODS: Multicenter retrospective analysis. The American College of Veterinary Internal Medicine oncology and internal medicine listservs were solicited for cases in which a chemotherapy OD occurred. RESULTS: Sixteen anthracycline cases were collected. Anthracycline ODs occurred because of an error in chemotherapy preparation (n = 9), or dose miscalculation (n = 7). The overall median OD was 1.9× (range, 1.4-10×) the prescribed amount. Most ODs were identified immediately after drug administration (n = 11), and the majority of patients were hospitalized on supportive care (n = 11) for an average of 8 days (range, 3-34 days). Adverse events after the OD included neutropenia (94%), thrombocytopenia (88%), anemia (63%), diarrhea (63%), anorexia (56%), vomiting (38%), lethargy (31%), and nausea (25%). Two patients did not survive the OD. High grade neutropenia was common and did not appear to be mitigated by the administration of filgrastim. CONCLUSIONS AND CLINICAL IMPORTANCE: All patients received supportive care after identifying the OD and death was uncommon. Further evaluation is needed to determine ideal therapeutic guidelines anthracycline OD.

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Published outcomes for dogs with specifically high-grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high-grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2-year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow-up 980 days) and 2 dogs were lost to follow-up. Death was considered MCT-related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.

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OBJECTIVE To estimate survival time for dogs with small intestinal adenocarcinoma (SIACA) following tumor excision with or without adjuvant chemotherapy and to identify factors associated with survival time. DESIGN Retrospective case series with a nested cohort study. ANIMALS 29 client-owned dogs with surgically resected, histologically diagnosed SIACA. PROCEDURES Medical records were reviewed and data collected regarding dog signalment; clinical signs; physical examination findings; PCV; serum total solids concentration; diagnostic imaging results; tumor size, location, and histologic characteristics (serosal extension, lymphatic invasion, surgical margins, and lymph node metastasis); type of adjuvant chemotherapy; NSAID administration; and survival time. Variables were assessed for associations with survival time and hazard rate via Kaplan-Meier and Cox proportional hazards analyses. RESULTS Overall median survival time for dogs with SIACA following tumor excision was 544 days (95% confidence interval, 369 to 719 days). Based on Kaplan-Meier estimates, the 1- and 2-year survival rates were 60% and 36%, respectively. On multivariate analysis, only age category was an independent predictor of survival over the follow-up period. Dogs < 8 years of age had a significantly longer median survival time (1,193 days) than dogs ≥ 8 years (488 days). Lymph node metastasis, adjuvant chemotherapy, NSAID administration, and other assessed variables were not associated with survival time. CONCLUSIONS AND CLINICAL RELEVANCE Findings suggested that SIACA in dogs carries a fair prognosis following excision, even when lymph node metastasis is present. Prospective studies are warranted to better characterize the effects of adjuvant chemotherapy or NSAID administration on survival time.

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OBJECTIVE To evaluate factors for associations with duration of first remission and survival time in dogs ≥ 14 years of age with stage III to V multicentric lymphoma. DESIGN Retrospective cohort study. ANIMALS 29 dogs ≥ 14 years of age with multicentric lymphoma treated with a chemotherapy protocol at dosages used for younger dogs (n = 22) or with prednisolone alone (7). PROCEDURES Various data were collected from the medical records, including treatment response and related adverse events. Survival analysis was performed to determine duration of first remission and survival time (from start of chemotherapy), and these outcomes were compared between various groupings. RESULTS The 7 (24%) dogs that received prednisolone alone had a median survival time of 27 days and were excluded from further analysis. Complete clinical remission was achieved in 21 of the 22 (95%) remaining dogs; 1 (5%) achieved partial remission. Median duration of first remission was 181 days. Anemic dogs had a briefer remission period (median, 110 days) than nonanemic dogs (median, 228 days). Median survival time for all 22 dogs was 202 days, with estimated 1- and 2-year survival rates of 31% and 5%, respectively. Six (27%) dogs had adverse events of chemotherapy classified as grade 3 or worse. CONCLUSIONS AND CLINICAL RELEVANCE Survival time was substantially longer in dogs treated with a chemotherapy protocol versus prednisolone alone. Findings suggested that the evaluated chemotherapy protocols for lymphoma were beneficial for and tolerated by very elderly dogs, just as by younger dogs, and need not be withheld, or dosages adjusted, because of age alone.

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BACKGROUND: Limited information is available regarding the treatment and outcome of dogs with epitheliotropic lymphoma. The disease typically has a poor prognosis. OBJECTIVES: To characterize the clinical signs, identify prognostic factors and evaluate the treatment outcome of dogs with epitheliotropic lymphoma. METHODS: A retrospective review of medical records from 2003 to 2015. Treatment details, tumour response and survival time were recorded for 148 dogs. Potential prognostic factors were evaluated for their statistical effect on median survival time. RESULTS: The overall median survival time for dogs was 264 days (cutaneous: 130 days; mucocutaneous/mucosal: 491 days). On multivariate analysis, a shorter median survival time was associated with the cutaneous form (P < 0.001) and the presence of multiple lesions (P < 0.001). Among 80 dogs with cutaneous lesions, chemotherapy treatment (P < 0.001) and having a solitary lesion (P < 0.001) were associated with longer median survival. In 72 dogs with multiple cutaneous lesions, chemotherapy intervention (P < 0.001), retinoid treatment (P = 0.001) and complete remission (P = 0.001) were associated with longer median survival. In 68 dogs with mucocutaneous/mucosal lesions, decreasing age (P = 0.020) and a solitary lesion (P = 0.015) were associated with longer median survival. CONCLUSION: Canine epitheliotropic lymphoma may be divided into cutaneous and mucocutaneous/mucosal forms. Solitary lesions have a better prognosis. Dogs with multiple lesions appear to benefit from chemotherapy and retinoid treatment, with those attaining complete remission having longer survival times. Multi-agent chemotherapy could be considered in dogs with cutaneous lesions that fail to respond to single-agent chemotherapy.

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OBJECTIVE To determine histologic and clinical factors associated with survival time in dogs with stage II splenic hemangiosarcoma treated by splenectomy and a chemotherapy protocol in which an anthracycline was alternated with lomustine. DESIGN Retrospective case series. ANIMALS 30 dogs with stage II splenic hemangiosarcoma. PROCEDURES Medical records of 3 facilities were reviewed to identify dogs treated for stage II splenic hemangiosarcoma between June 2011 and October 2014. Information collected included signalment, disease staging data, whether anemia was present, date of splenectomy, chemotherapy protocol, adverse effects, and date of death or last follow-up. Histologic slides were reviewed and scored by pathologists. Associations between variables of interest and survival data were evaluated statistically. RESULTS Median survival time for all dogs was 158 days (range, 55 to 560 days), and the 1-year survival rate was 16%. On multivariate analysis, only the histologically determined mitotic score was significantly associated with survival time. The median survival time of 292 days for dogs with a mitotic score of 0 (< 11 mitoses/10 hpf; n = 9) was significantly longer than that for dogs with higher scores (indicating higher mitotic rates); the 1-year survival rate for these dogs was 42%. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that future studies should take histologic factors, particularly mitotic rate, as well as tumor stage into account when assessing treatment effects on survival time of dogs with splenic hemangiosarcoma.

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OBJECTIVE To determine the incidence of sterile hemorrhagic cystitis (SHC) in tumor-bearing dogs concurrently treated with oral metronomic cyclophosphamide chemotherapy and furosemide. DESIGN Retrospective case series. ANIMALS 55 dogs. PROCEDURES Record databases of 2 specialty practices were searched to identify dogs treated with oral metronomic cyclophosphamide chemotherapy in conjunction with furosemide for a minimum of 28 days between January 2009 and December 2015. Information extracted from the records included signalment, tumor diagnosis, cyclophosphamide and furosemide dosages, and concurrent medications. Confirmed SHC was defined as the presence of gross or microscopic hematuria and clinical signs associated with lower urinary tract disease in the absence of infection or neoplasia of the urinary tract; the definition for suspected SHC was the same, except the absence of infection or neoplasia of the urinary tract was not confirmed. RESULTS Cyclophosphamide dosage varied from 6.5 to 18.6 mg/m2 once daily to 6.3 to 49.2 mg/m2 every other day. Median duration of cyclophosphamide administration was 272 days (range, 28 to 1,393 days). Median cumulative dose of cyclophosphamide administered was 2,898 mg/m2 (range, 224 to 14,725 mg/m2). Median furosemide dose was 1.4 mg/kg (0.64 mg/lb). Confirmed or suspected SHC was identified in 2 of 55 (3.6%) dogs. Cyclophosphamide administration was discontinued for the dog with confirmed SHC but not the dog with suspected SHC. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of furosemide in conjunction with oral metronomic cyclophosphamide chemotherapy was associated with a low incidence of SHC, which suggested that furosemide may protect against cyclophosphamide-induced SHC.

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CASE DESCRIPTION 4 dogs with a slow-growing mass in the cervical region were evaluated. CLINICAL FINDINGS All dogs had no clinical signs at the time of the evaluation. There was no apparent evidence of visceral metastases or other primary tumor based on available CT or MRI data for any dog. TREATMENT AND OUTCOME For each dog, surgery to remove the mass was performed. Histologic examination of the excised tissue revealed a completely excised grade 1 or 2 lymph node hemangiosarcoma. All dogs received adjuvant chemotherapy; 2 dogs underwent curative intent chemotherapy, 1 dog underwent metronomic treatment with cyclophosphamide, and 1 dog underwent metronomic treatment with chlorambucil. The survival time was 259 days in 1 dog; 3 dogs were still alive 615, 399, and 365 days after surgery. CLINICAL RELEVANCE Primary nodal hemangiosarcoma in dogs is a rare and, to the authors' knowledge, previously undescribed disease that appears to develop in the cervical lymph nodes as a slow-growing mass or masses. Surgical excision and adjunct treatment resulted in long survival times for 3 of the 4 dogs of the present report. Given the aggressive biologic behavior of hemangiosarcomas in other body locations, adjunct chemotherapy should be considered for affected dogs, although its role in the cases described in this report was unclear. Additional clinical information is required to further characterize the biologic behavior of this tumor type and determine the expected survival times and associated risk factors in dogs.

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Overall, canine lymphoma remains one of the most chemotherapy-responsive cancers in the dog. In addition to the stage and the substage of disease, T cell phenotype is the most consistently important prognostic factor. T cell lymphoma (TCL) in dogs is a heterogeneous disease; dogs with a separate entity of indolent TCL can have a considerably better prognosis than dogs with other forms of lymphoma, and indolent TCL may not always require immediate treatment. In contrast, high-grade TCL is an aggressive disease, and when treated with CHOP-based protocols, dogs with this high-grade TCL have a complete remission rate as low as 40 per cent, relapse earlier and have shorter survival time than dogs with a comparable stage, high-grade B cell lymphoma. This review describes the different disease entities that comprise canine TCL, discusses prognosis for each and treatment options that appear to give the best outcomes.

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The immunophenotype of canine non-indolent lymphoma has prognostic value; dogs with T cell lymphoma have a poorer response rate and shorter survival times than dogs with B cell lymphoma. This study sought to retrospectively evaluate prognostic factors for complete remission (CR), progression free survival (PFS) and overall survival time (OST) in 70 dogs with T cell lymphoma treated with an alkylator-rich, combination protocol. The overall remission was 72.9%; 45 dogs (64.3%) achieved CR and six (8.6%) achieved partial remission. Dogs that were neutropenic at diagnosis were significantly more likely to achieve CR. The median overall PFS was 175 days; 1, 2 and 3 year PFS were 26.8%, 15.8%, and 12.6%, retrospectively, after commencing chemotherapy. Median PFS was significantly longer for dogs that achieved CR. Median OST was 237 days. The 1, 2 and 3 year survival rates were 31%, 20.2% and 11.5%, retrospectively, after commencing chemotherapy. The median OST was significantly longer for dogs that achieved CR and significantly shorter for Boxers and those in substage b at diagnosis. More than 30% of dogs treated with this protocol survived >1 year, suggesting that favourable outcomes and longer survival are possible for a proportion of dogs with T cell lymphoma.

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Canine appendicular osteosarcoma is an important clinical problem in veterinary medicine. Current standard therapy includes amputation followed by chemotherapy, which improves outcomes; however the percentage of long-term survival is still relatively low at 15-20%. Established prognostic factors include serum alkaline phosphatase level, histologic grade, and lymphocyte and monocyte counts. We used a protocol with shorter inter-treatment intervals than standard, but which we expected to still be well-tolerated, based on drugs known to be active agents, with the aim of improving outcomes by increasing dose intensity. Thirty-eight dogs with confirmed appendicular osteosarcoma and no pulmonary metastases that underwent amputation followed by this chemotherapy protocol were retrospectively evaluated. The median survival time was 317 days and 1- and 2-yr survival percentages were 43.2% and 13.9%, respectively. Toxicity was comparable to that seen with other standard dose protocols, with 5.2% of dogs hospitalized for complications that resolved with supportive care and no chemotherapy-related mortality. Serum alkaline phosphatase level (normal or high) (p = 0.004) and whether or not chemotherapy was completed (p = 0.001) were found to significantly impact survival time on multivariate analysis. Outcomes were similar to those reported with most other published chemotherapy protocols for dogs with this disease.

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The devil facial tumor disease (DFTD) is having a devastating impact on Tasmanian devils (Sarcophilus harrisii) (devils) in the wild. Only a single study has been published regarding treatment of DFTD, where vincristine was not found to be an effective chemotherapeutic agent. In the current study, devils were treated with escalating dosages of carboplatin (8-26 mg/kg) (n = 13) and doxorubicin (0.75-1.0 mg/kg) (n = 5). Dosages for carboplatin (20 mg/kg) and doxorubicin (1.0 mg/kg) were identified as maximally tolerated dosages. Limiting toxicities for carboplatin were anorexia and weight loss (gastrointestinal signs) and azotemia. Limiting toxicities for doxorubicin were neutropenia, anorexia and weight loss. None of the treated devils responded to either drug, suggesting that, based on the clonality of this tumour, it is unlikely that either drug individually or in combination would be effective treatments for DFTD. These results, however, provide valuable information for practitioners who may choose to treat other neoplastic diseases in the devil or other marsupials. In addition, these results show that even drugs that are metabolized and excreted in the same manner can be tolerated to different degrees by the same species.

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BACKGROUND: Epidemiologic studies of companion animals offer an important opportunity to identify risk factors for cancers in animals and humans. Canine malignant lymphoma (CML) has been established as a model for non-Hodgkin's lymphoma (NHL). Previous studies have suggested that exposure to environmental chemicals may relate to development of CML. METHODS: We assessed the relation of exposure to flea and tick control products and lawn-care products and risk of CML in a case-control study of dogs presented to a tertiary-care veterinary hospital (2000-2006). Cases were 263 dogs with biopsy-confirmed CML. Controls included 240 dogs with benign tumors and 230 dogs undergoing surgeries unrelated to cancer. Dog owners completed a 10-page questionnaire measuring demographic, environmental, and medical factors. RESULTS: After adjustment for age, weight, and other factors, use of specific lawn care products was associated with greater risk of CML. Specifically, the use of professionally applied pesticides was associated with a significant 70% higher risk of CML (odds ratio(OR)=1.7; 95% confidence interval (CI)=1.1-2.7). Risk was also higher in those reporting use of self-applied insect growth regulators (OR=2.7; 95% CI=1.1-6.8). The use of flea and tick control products was unrelated to risk of CML. CONCLUSIONS: Results suggest that use of some lawn care chemicals may increase the risk of CML. Additional analyses are needed to evaluate whether specific chemicals in these products may be related to risk of CML, and perhaps to human NHL as well.

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ETHICAL ISSUES: Caring for cancer patients presents many ethical issues for veterinarians and other veterinary health workers. The issues that most veterinarians think of relate to management of the patient when the owners' preferences for treatment do not appear to be in the animal's best interest, as well as concerns about toxicities and about costs of veterinary services (advanced imaging, surgery, radiation therapy and chemotherapy). While not limited to the veterinary profession, we are more often faced with dilemmas about the appropriateness of palliative care and decisions about euthanasia than our medical colleagues. Equally important are the ethics of not treating patients, and the integration of unproven and alternative strategies into conventional care. A separate ethical issue arises from investigational therapies and research. Less often considered, but nonetheless relevant, are the ethics of suboptimal evaluation (staging) of patients prior to treatment, or of not informing owners about all the options available. CLIENT COMMUNICATION: Ethical veterinary care is intertwined with good client communication. Without good communication, it is impossible, for example, to gain informed consent; and without informed consent, the ethics of cancer treatment are uncertain. GOAL: This article, which draws in part on published research, where stated, and otherwise on the author's personal experiences/opinions and those of veterinary colleagues, is intended to provoke further thought and discussion on the ethics of caring for our cancer patients.

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Low-grade alimentary lymphoma (LGAL) was diagnosed by histological and immunohistochemical evaluation of full-thickness biopsies from multiple regions of the gastrointestinal tract collected during exploratory laparotomy in 17 cats. The most common clinical signs were weight loss (n=17) and vomiting and/or diarrhoea (n=15). Clinical signs were chronic in 11 cases. Abdominal palpation was abnormal in 12 cats, including diffuse intestinal thickening (n=8), an abdominal mass due to mesenteric lymph node enlargement (n=5) and a focal mural intestinal mass (n=1). The most common ultrasonographic finding was normal or increased intestinal wall thickness with preservation of layering. Ultrasound-guided fine-needle aspirates of mesenteric lymph nodes (n=9) were incorrectly identified as benign lymphoid hyperplasia in eight cats, in which the histological diagnosis from biopsies was lymphoma. There was neoplastic infiltration of more than one anatomic region of the gastrointestinal tract in 16/17 cats. The jejunum (15/15 cats) and ileum (13/14 cats), followed by the duodenum (10/12 cats), were the most frequently affected sites. Twelve cats were treated with oral prednisolone and high-dose pulse chlorambucil, two with a modified Madison-Wisconsin multiagent protocol and three with a combination of both protocols. Thirteen of the 17 cats (76%) had complete clinical remission with a median remission time of 18.9 months. Cats that achieved complete remission had significantly longer median survival times (19.3 months) than cats that did not achieve complete remission (n=4) (4.1 months; P=0.019). The prognosis for cats with LGAL treated with oral prednisolone in combination with high-dose pulse chlorambucil is good to excellent.

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BACKGROUND: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy. HYPOTHESIS: Survival will be prolonged in dogs receiving BAY 12-9566. ANIMALS: The study included 303 dogs with appendicular osteosarcoma. METHODS: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy. RESULTS: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased. CONCLUSIONS AND CLINICAL IMPORTANCE: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.

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OBJECTIVE: To evaluate survival times and palliative effects associated with the use of samarium Sm 153 lexidronam in dogs with primary bone tumors. DESIGN: Retrospective case series. ANIMALS: 35 dogs with primary appendicular (n = 32) or axial (3) bone tumors. PROCEDURES: 1 to 4 doses of samarium Sm 153 lexidronam were administered at a rate of 37 MBq/kg (16.8 MBq/lb), IV. Response to treatment, measured by lameness improvement, and survival time were determined. RESULTS: Of the 32 dogs with appendicular tumors, 20 (63%) had an improvement in the severity of lameness 2 weeks after administration of the first dose of radioactive samarium, 8 (25%) had no change in the severity of lameness, and 4 (12%) had a worsening. Overall median survival time was 100 days, with 3 dogs (8.6%) alive after 1 year. Median survival time for the 32 dogs with appendicular tumors was 93 days, with 3 (9.4%) alive after 1 year. This was not significantly different from the median survival time of 134 days for a historical cohort of 162 dogs with appendicular osteosarcoma that underwent amputation as the only treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that samarium Sm 153 lexidronam may be useful in the palliation of pain in dogs with primary bone tumors that are not candidates for curative-intent treatment.

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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.

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