Pulmonary fibrosis after high cumulative dose nitrosourea chemotherapy in a cat

Small to intermediate cell alimentary lymphoma was diagnosed in a cat after abdominal exploratory surgery with no prior history of pulmonary disease. Initial response to several chemotherapy regimens was poor, but a long‐term remission was achieved with CCNU (lomustine) and corticosteroid therapy. After receiving a total cumulative CCNU dose of 552 mg m^?2 over 12 months, an acute episode of respiratory distress occurred and the cat died. Necropsy identified severe diffuse pulmonary fibrosis and no signs of lymphoma. This is the first report of pulmonary fibrosis following high cumulative dose nitrosourea chemotherapy in a cat.     

Phase I clinical trial evaluating STI571 in tumor bearing cats

Introduction: STI571 (Gleevec, imatinib mesylate) is a receptor tyrosine kinase inhibitor with selectivity for Bcr‐Abl, platelet‐derived growth factor (PDGF), stem cell factor (SCF), and c‐Kit. Side effects with use in humans include vomiting, diarrhea, nausea, myalgia, edema, and cutaneous reactions. Renal and hepatic toxicity have also been reported. In dogs, there is significant hepatic toxicity at sub‐clinical doses. The purpose of this prospective study was to determine the toxicity level and potential treatment protocol in tumor bearing cats. Methods: A phase I clinical trial was performed in client owned cats using an escalating dose of STI571 in tumor bearing cats. Cats included in the study had a histologic diagnosis of fibrosarcoma or other tumors and were staged with CBC, biochemical profile, thoracic radiographs, and abdominal ultrasound. None of the cats received concurrent chemotherapy, but those previously treated with surgery, radiation therapy, or chemotherapy, were not excluded. The initial starting dose was 5 mg/cat PO SID and was gradually increased to 10 and 20 mg/cat PO SID at a 2–6 week interval depending on laboratory work and disease progression. A repeat physical examination, CBC, and biochemical profile, were performed every 2 weeks for 2 rechecks, then every 4 weeks. Results: Six cats were enrolled in the study. Four cats had oral squamous cell carcinoma, and two cats had cutaneous fibrosarcoma. One cat demonstrated leukocytosis, increased liver enzymes, and signs of acute renal failure two weeks after initiating therapy (5 mg PO SID). No dose escalation was made in this cat. Five cats endured dose escalations of 10 mg PO SID in two cats and 20 mg PO SID in three cats and were treated for 2–4 months. None of these cats experienced any signs of toxicity as measured by CBC and biochemical profile. Conclusions: Only one cat experienced toxicity that may have been associated with low dose administration of STI571. As most cats tolerated the drug without an adverse effect, further evaluation of STI571 in a phase II clinical trial is warranted.     

P‐59 Three cases of opportunistic dermatoses associated with internal diseases in cats

Opportunistic dermatoses can occur in case of immunosuppressive diseases. The first case was a 12‐year‐old domestic short‐haired cat suffering from diabetes with a phaeohyphomycosis due to Scytalidium spp.associated with cutaneous hemangiosarcoma. A painless and ulcerated nodule was observed on a digit with fistulous tracts over the metatarsal joint. Histopathological examination of the nodule revealed a hemangiosarcoma in which brownish fungal colonies were found. Itraconazole (5 mg/kg twice daily), then amputation, allowed 12 months of survival (pulmonary metastases). The second case concerned a 13‐year‐old Siamese cat with cheyletiellosisassociated with spontaneous Cushing's disease and diabetes mellitus. This cat exhibited scales and miliary dermatitis on the trunk associated with polyuria, polydipsia and a pot‐belly. Acetate tape impression showed Cheyletiella blakei mites and eggs. Blood analysis revealed diabetes mellitus and spontaneous hyperadrenocorticism. The owner refused treatment. The third case was a 14‐year‐old domestic short‐haired cat with generalized demodicosis associated with iatrogenic Cushing's disease and diabetes mellitus. Long‐acting glucocorticoids had been used for treatment of plasma cell stomatitis for 5 years. This cat exhibited erythema, scales, self‐induced alopecia, thin skin and moderate pruritus associated with polyuria and polydipsia. Cutaneous lesions principally developed on the abdomen and flanks. Skin scrapings and trichogram showed numerous Demodex cati mites. Routine blood work demonstrated diabetes mellitus and iatrogenic Cushing's disease. Treatment was based on insulin therapy, milbemycin oxime (1 mg/kg once daily) and chlorambucil (0.2 mg/kg once daily). The demodicosis was cured after 4 months, but the cat died of cutaneous and ocular herpesvirus infection 10 months later. Funding: Self‐funded.     

Phase II clinical evaluation of lomustine chemotherapy for feline vaccine‐associated sarcoma

Treatment of feline vaccine‐associated sarcoma (VAS) is challenging, in part due to the high likelihood of tumour recurrence despite aggressive local therapy. Lomustine is potentially an attractive agent to add to the current treatment armamentarium. In this de‐escalating phase I/II prospective trial, 28 cats with measurable VAS were treated at target dosages of 38–60 mg m^?2 every 3 weeks until disease progression. The overall response rate was 25%, with a median progression‐free survival and median duration of response of 60.5 and 82.5 days, respectively. Haematologic toxicity, specifically cumulative neutropenia, was significant, and dose reductions and treatment delays were common. Although these data support further investigation of lomustine for the treatment of VAS, safe, multidosing protocols must first be determined.     

Phase I Dose Escalation of Single‐Agent Vinblastine in Dogs

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

Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m^?2 (range, 150–300 mg m^?2) and 4 (range, 2–11), respectively. The overall median progression‐free survival for all dogs was 259 days [95% confidence interval (CI₉₅), 119–399 days]. The first progression‐free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI₉₅, 247–633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia.     

The use of nuclear imaging for a mixed C cell microfollicular carcinoma of the thyroid gland in a mature horse

A 15‐year‐old Boerperd stallion presented for thyroid enlargement associated with inappetance. Ultrasonographic examination of the thyroid gland revealed an enlarged left lobe, which, on cytological examination, contained numerous anaplastic cells. A mixed C cell microfollicular thyroid carcinoma was diagnosed following histopathological examination of the excisional biopsy specimen. In order to determine metastasis, pulmonary radiographs revealed a poorly‐marginated soft tissue opacity caudo‐dorsal to the cardiac silhouette. Thyroid and pulmonary scintigraphy was performed comparing ^99mTc‐sestamibi with ^99mTc‐pertechnetate and no metastasis was detectable. Following hemithyroidectomy, the stallion made a full recovery without the need for neoadjuvant chemotherapy. Six months later, repeated thyroid and pulmonary scintigraphy using ^99mTc‐sestamibi was normal.     

Vincristine sulfate as single-agent chemotherapy in a dog and a cat with malignant neoplasms

A 12-year-old 4-kg spayed domestic shorthair cat with a poorly differentiated fibrosarcoma of the rostral aspect of the mandible and an 11-year-old 13-kg castrated dog of mixed breeding with pulmonary metastatic hemangiosarcoma were treated with 0.5 mg of vincristine sulfate/m2 of body surface, IV, weekly. Three months after beginning treatment, both animals had complete clinical remission. The role of this vinca alkaloid as a single agent for malignant neoplasms has seldom been discussed in the veterinary scientific literature. The results of these two cases indicate that single-agent vincristine sulfate chemotherapy is effective in the treatment of feline fibrosarcoma and canine hemangiosarcoma.     

Hemorrhagic diathesis and bone marrow aplasia secondary to lomustine overdose in a dog

A 9‐year‐old mixed breed 13 kg spayed female dog was presented for evaluation of two masses in the right abdominal mammary gland region. Surgery was conducted to excise the masses. A grade I complex mammary gland carcinoma and high grade (grade III) mast cell tumor with an inguinal lymph node metastasis were diagnosed. Forty‐seven days after the surgical procedure, the mast cell tumor relapsed, and neoadjuvant treatment with lomustine (81 mg/m²) was prescribed. Thirteen days from initiation of lomustine therapy, the dog was re‐presented to the hospital with bloody diarrhea, hematemesis, epistaxis, an elevated rectal temperature, depression, severe dehydration, and marked dyspnea. The CBC showed severe thrombocytopenia and leukopenia. According to the owner, lomustine (45mg per os [PO]) was mistakenly administered daily for 10 consecutive days (total dose, 810 mg/m²). The dog died and a necropsy was performed. The main gross lesions consisted of severe multifocal hemorrhages in multiple organs, especially in the digestive system. Histopathologic evaluation revealed disseminated hemorrhages, as well as marked bone marrow aplasia. This report describes the clinical, hematologic, gross, and histologic findings in a fatal case of lomustine overdose in a dog.     

Retrospective comparison of three doses of metronomic chlorambucil for tolerability and efficacy in dogs with spontaneous cancer

The study hypothesis is that higher doses of metronomic (low‐dose) chlorambucil will improve outcome without significantly worsening adverse events (AE). Retrospectively, 88 dogs were screened to assess for tolerability and response to chlorambucil utilizing retrospective and prospective data sets, comparing metronomic oral daily doses 4, 6 and 8 mg m². There were 78 and 70 dogs in the tolerability and efficacy portions, respectively. The severity of gastrointestinal (GI) AE was significantly worse, and time to development of GI events was significantly shorter at 6 mg m² than at 4 mg m² (both P < 0.001). Chlorambucil was discontinued earlier in the dogs treated at the 6 mg m² doses than in the dogs treated at 4 mg m² (P = 0.015). Thrombocytopenia occurred significantly earlier at 8 mg m² than at 4 mg m² (P = 0.017). Higher doses of metronomic (low‐dose) chlorambucil did not provide improved responses and were associated with more AE.     

Reversible pulmonary hypertension in a cat

A 13-year-old, neutered female domestic shorthair cat was presented for sudden respiratory distress following palliative radiotherapy and the combined administration of a single dose of carboplatin for the treatment of recurrent fibrosarcoma. Clinical and radiographic findings were suggestive of pleural effusion. Echocardiography revealed marked right-sided cardiac enlargement associated with tricuspid regurgitation and Doppler evidence of pulmonary hypertension. After 25 days of treatment for congestive heart failure and suspected pulmonary thromboembolism, clinical signs and echocardiographic and Doppler evidence of right-sided cardiac enlargement and pulmonary hypertension had completely resolved. To the best of the authors' knowledge, this is the first report of reversible pulmonary hypertension, likely secondary to pulmonary thromboembolism, in a cat.     

A phase I clinical trial evaluating imatinib mesylate (Gleevec) in tumor-bearing cats

A phase I clinical trial evaluating the toxicity of orally-administered imatinib mesylate was performed in 9 tumor-bearing cats. Imatinib is a small molecule, tyrosine kinase inhibitor, which selectively blocks the function of overexpressed proteins associated with various malignancies. Cats included in the study had diagnoses of fibrosarcoma, squamous cell carcinoma, and mast cell tumor, and each cat was staged using CBC and serum biochemistry; urinalysis, thoracic radiographs, and abdominal ultrasonography were performed in some cats. Most cats were treated previously by surgery, radiation therapy, chemotherapy, or some combination of these treatments. None of the cats received any concurrent chemotherapy. Six cats were treated with imatinib mesylate at 1-2 mg/kg PO q24h. Dose escalations were made to 2, 4, and 10 mg/kg PO q24h in 5 cats. Two cats started therapy at 10 mg/kg PO q24h, and 1 cat started therapy at 15 mg/kg PO q24h; all 3 cats remained at these dosages. No signs of toxicity, as evaluated by CBC and serum biochemistry, were noted in 8 of the 9 cats, and minimal gastrointestinal toxicity was observed. Due to the low frequency of adverse effects, further evaluation of imatinib is ongoing at a dosage of 10 mg/kg PO q24h.     

The effect of moderate hypovolemia on cardiopulmonary function in dogs

Objective: To collate canine cardiopulmonary measurements from previously published and unpublished studies in instrumented, unsedated, normovolemic and moderately hypovolemic dogs. Design: Collation of data obtained from original investigations in our research laboratory. Setting: Research laboratory, School of Veterinary Medicine. Subjects: Sixty‐eight dogs. Interventions: Subjects were percutaneously instrumented with an arterial catheter and a thermodilution cardiac output catheter. A femoral artery catheter was percutaneously placed for blood removal. Measurements and main results: Body weight, arterial and mixed‐venous pH and blood gases, arterial, pulmonary arterial, pulmonary artery occlusion, and central venous blood pressure, cardiac output, and core body temperature were measured. Body surface area, bicarbonate concentration, standard base excess, cardiac index (CI), stroke volume, systemic and pulmonary vascular resistance, left and right ventricular work and stroke work indices, left and right rate‐pressure product, alveolar PO₂, alveolar–arterial PO₂ gradient, arterial and mixed‐venous and pulmonary capillary oxygen content, oxygen delivery, oxygen consumption, oxygen extraction, venous admixture, arterial and venous blood carbon dioxide content, arterial–venous carbon dioxide gradient, carbon dioxide production were calculated. In 68 dogs, hypovolemia sufficient to decrease mean arterial blood pressure (ABPm) to an average of 62 mmHg, was associated with the following changes: arterial partial pressure of carbon dioxide (PaCO₂) decreased from 40.0 to 32.9 mmHg; arterial base deficit (BDa) increased from ?2.2 to ?6.3 mEq/L; lactate increased from 0.85 to 10.7 mm /L, and arterial pH (pHa) did not change. Arterial partial pressure of oxygen (PaO₂) increased from 100.5 to 108.3 mmHg while mixed‐venous PO₂ (PmvO₂) decreased from 49.1 to 34.1 mmHg. Arterial and mixed‐venous oxygen content (CaO₂ and CmvO₂) decreased from 17.5 to 16.5 and 13.8 to 9.6 mL/dL, respectively. The alveolar–arterial PO₂ gradient (A‐a PO₂) increased from 5.5 to 8.9 mmHg while venous admixture decreased from 2.9% to 1.4%. The ABPm decreased from 100 to 62 mmHg; pulmonary arterial pressure (PAPm) decreased from 13.6 to 6.4 mmHg; and pulmonary arterial occlusion pressure (PAOP) decreased from 4.9 to 0.1 mmHg. CI decreased from 4.31 to 2.02 L/min/m². Systemic and pulmonary vascular resistance (SVRI and PVRI) increased from 1962 to 2753 and 189 to 269 dyn s/cm⁵, respectively. Oxygen delivery (DO₂) decreased from 787 to 340 mL/min/m² while oxygen consumption (VO₂) decreased from 172 to 141 mL/min/m². Oxygen extraction increased from 20.9% to 42.3%. Conclusions: Moderate hypovolemia caused CI and oxygen delivery to decrease to 47% and 42% of baseline. Oxygen extraction, however, doubled and, therefore, oxygen consumption decreased only to 82% of baseline.     

Safety evaluation of combination carboplatin and toceranib phosphate (Palladia) in tumour‐bearing dogs: A phase I dose finding study

Combining conventional cytotoxic maximum tolerated dose (MTD) chemotherapy with low‐dose metronomic and/or anti‐angiogenic agents is a exciting area of oncologic research. The objective of this study was to establish the MTD, safety and adverse event (AE) profile of 1 such drug combination. This prospective phase I dose‐finding clinical trial assumed an open‐label 3 + 3 cohort design. Client‐owned dogs with 1 or more cytologically and/or histologically confirmed and macroscopically measurable, naive or recurrent, malignant tumours, were enrolled. No preference for tumour histology, grade or stage was expressed. Toceranib was administered at a dose of 2.75 mg kg^?1 by mouth (PO) every other day (EOD), and carboplatin administered intravenously (IV) every 21 days at a starting dose of 200 mg m^?2. A total of 25% dose escalation was proposed for carboplatin, to a maximum of 300 mg m^?2. AEs were graded according to the Veterinary Cooperative Oncology Group's common terminology criteria for AEs (VCOG‐CTCAE). Grade 3 haematologic or gastrointestinal AEs were nominated dose‐limiting. Response to therapy was evaluated according to the VCOG's revised RECIST criteria. Eleven dogs were enrolled. Tumour histologies included sinonasal carcinoma, osteosarcoma, thyroid carcinoma, melanoma and apocrine gland anal sac adenocarcinoma. MTDs of carboplatin and toceranib were identified as 200 mg m^?2 IV every 21 days and approximately 2.75 mg kg^?1 PO EOD, respectively. The dose‐limiting toxicity was neutropenia. Two dogs experienced a partial response, and 6 maintained stable disease. Combination carboplatin and toceranib chemotherapy was well‐tolerated. Clinical benefit was observed in most cases. This protocol warrants further investigation in phase II/III trials.     

The pharmacokinetics of cytarabine administered at three distinct subcutaneous dosing protocols in dogs with meningoencephalomyelitis of unknown origin

The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara‐C) protocol (50 mg/m² subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m² subcutaneous dose and two 100 mg/m² subcutaneous doses every 12 hr). Four client‐owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara‐C protocols with a 21‐day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara‐C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m², respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m², respectively.     

Furosemide administration onehour before bone scintigraphy examination in horses does not improve the image quality or reduce the radiation dose rate

This prospective, cross‐sectional, pilot study aimed to investigate the effects of furosemide as a diuretic on the image quality of bone scintigraphy performed using ^99mTc‐HDP and to investigate the impact of furosemide on the radiation dose rate. Thirty‐one horses undergoing bone scintigraphy were included. The horses were divided into the control (n = 14) and furosemide group (n = 17), which received 1 mg/kg furosemide intravenously 1 h post ^99mTc‐HDP administration. The image quality was assessed subjectively and semi‐quantitatively. The bone‐to‐soft tissue (B:S) ratio was calculated from the counts per pixel of regions of interest (ROI) positioned over the left radial diaphysis (bone ROI) and its caudal soft tissue area (soft tissue ROI). The radiation rate dose (μSv/h) of both groups was measured at 0, 3, 6, 12, 18, and 24 h post ^99mTc‐HDP administration at a distance of 0, 30, and 100 cm from the head, kidney, and pelvis. The results showed no significant differences in the B:S ratio or the radiation dose rate observed between the groups. However, the radiation dose rate decreased by 56% at 3 h post ^99mTc‐HDP administration and keeping a distance of 30 cm reduced the radiation dose rate by 65%. Administering furosemide does not improve the image quality or reduce the radiation dose rate. The authors recommend commencing with bone scintigraphy 3 h post ^99mTc‐HDP administration and keeping at least a distance of 30 cm from the horse to reduce the staff radiation dose.     

Low-dose cyclophosphamide selectively decreases regulatory T cells and inhibits angiogenesis in dogs with soft tissue sarcoma

Background: Low‐dose, continuous (metronomic) chemotherapy improves tumor control by inhibiting tumor angiogenesis and suppressing regulatory T cells (Treg) in mice and humans. The effects of metronomic chemotherapy on Treg and tumor angiogenesis in dogs has not been investigated previously. Objective: To determine whether metronomic cyclophosphamide (CYC) therapy decreases Treg or exhibits antiangiogenic activity or both in dogs with soft tissue sarcoma (STS). We hypothesized that Treg numbers would be increased in dogs with STS and that continuous dosing of CYC would decrease Treg in a dose‐dependent manner, as well as exhibit antiangiogenic activity. Animals: Eleven client‐owned dogs with grade I or II STS. Twenty‐one healthy dogs were used as controls. Methods: Prospective, open, clinical trial. Dogs with STS were enrolled in 2 dose cohorts and administered CYC at 12.5 or 15 mg/m² PO once daily for 28 days. Whole blood and tumor biopsy specimens were obtained on days 0, 14, and 28 to assess changes in T lymphocyte subsets by flow cytometry and tumor microvessel density (MVD), respectively. Results: Administration of CYC at 12.5 mg/m²/d significantly decreased the number of Treg from days 0 to 28, but there was no change in the percentage of Treg or tumor MVD. In dogs that received CYC at 15.0 mg/m²/d, both the number and percent of Treg as well as tumor MVD were significantly decreased over 28 days. Conclusions: CYC administered at 15 mg/m²/d should be used in further studies examining the antitumor properties of low‐dose CYC in dogs.     

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.     

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

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

Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma

Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi‐institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post‐radiation temozolomide in dogs with chemotherapy‐naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m^?2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post‐radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT.