Tolerability of Gemcitabine and Carboplatin Doublet Therapy in Cats with Carcinomas

Background: This study was performed to determine the toxicity of gemcitabine-carboplatin doublet therapy in cats with carcinomas.
Hypothesis: Gemcitabine and carboplatin are safe in tumor-bearing cats.
Animals: Twenty cats with spontaneously occurring carcinomas.
Methods: A cohort of 6 cats received gemcitabine (2 mg/kg IV) on days 1, 8, and 15 and carboplatin (10 mg/kg IV) immediately after gemcitabine on day 1 of a 21-day cycle. A 2nd cohort of 14 cats received carboplatin 4 hours after gemcitabine on day 1 and gemcitabine on day 8 but not day 15. The cycles were repeated every 21 days.
Results: Cats in the 1st cohort received a median of 3.75 cycles per animal (range, 1–6). Two cats (33.3%) developed grade 3 or 4 neutropenia, 1 (16.7%) grade 4 thrombocytopenia, and 1 (16.7%) grade 3 gastrointestinal toxicity. Gemcitabine dose reductions and treatment delays occurred in 1 and 4 cats, respectively. Cats in the 2nd cohort received a median of 2 cycles per animal (range, 0.5–10). Two cats (14.3%) had grade 3 or 4 neutropenia and 1 (7.1%) had grade 3 and 4 gastrointestinal toxicity. One cat required gemcitabine dose reduction and 6 had treatment delays. In the 2nd cohort, of 11 cats with measurable tumors, there was 1 complete response (pancreatic carcinoma) and 1 partial response (squamous cell carcinoma, receiving concurrent nonsteroidal anti-inflammatory drugs).
Conclusions and Clinical Importance: Gemcitabine-carboplatin combination appears moderately well tolerated in tumor-bearing cats. Minimal patient benefit suggests that alternative schedules or combinations of gemcitabine with other agents should be explored.     

Adverse Effects of Concurrent Carboplatin Chemotherapy and Radiation Therapy in Dogs

Background: Concurrent chemo- and radiotherapy improves outcome of certain human neoplasms but with increased signs of toxicity. Reports on adverse effects of concurrent chemo- and radiotherapy in the veterinary literature are scant.
Objective: To report adverse hematologic and gastrointestinal effects of combined carboplatin and radiation therapy in dogs.
Animals: Client-owned dogs with spontaneously occurring neoplasia.
Methods: Retrospective case study. Medical records of 65 dogs were reviewed. Criteria for inclusion were administration of radiation according to 1 of 3 fractionation schemes (19 × 3, 16 × 3, or 12 × 4 Gy) and administration of at least 1 concurrent carboplatin treatment at a dosage of 200–300 mg/m². Dog and treatment-related variables were analyzed for association with signs of intoxication.
Results: Median carboplatin dosage was 200 mg/m² (range, 200–250 mg/m²). Twelve of 58 dogs (21%) developed grade 3 or 4 neutropenia. Eleven of 56 dogs (20%) developed grade 3 or 4 thrombocytopenia. Six of 62 dogs (10%) developed grade 3, 4, or 5 gastrointestinal toxicosis. Analysis of association of dog and treatment-related variables with signs of intoxication was hampered by the small numbers of dogs in individual groups, and no statistically significant associations were found.
Conclusions and Clinical Importance: Combined modality therapy resulted in myelosuppression and gastrointestinal toxicosis. Future studies are needed to determine whether the potential benefit of combined modality therapy outweighs the risk of decreasing chemotherapy and radiation treatment intensity.     

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.     

Dacarbazine as Single-Agent Therapy for Relapsed Lymphoma in Dogs

Background: Multidrug resistance is the most common cause of treatment failure in dogs with multicentric lymphoma. 5-(3,3-Dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) is an atypical alkylator used as standard treatment in human Hodgkin's lymphoma, and has been effective in combination treatment to treat resistant lymphoma in dogs. However, no data are available on the use of DTIC as a single agent in the treatment of relapsed canine lymphoma.
Hypothesis: Single-agent DTIC is effective and safe in treating dogs with lymphoma that relapsed or failed to respond to previous chemotherapy.
Animals: Forty client-owned dogs with relapsed lymphoma.
Methods: Dogs were eligible for the retrospective study if they had a histologically or cytologically confirmed diagnosis of lymphoma and had relapsed. Dogs received DTIC (800–1,000 mg/m² every 2–3 weeks as a 4–5-hour IV infusion) and were evaluated for response rate and duration. Hematologic and gastrointestinal toxicity was assessed.
Results: The overall response rate for dogs being treated with DTIC was 35% (14 dogs) with a median progression-free interval of 43 days. Thirteen dogs had a partial response and 1 dog had a complete response. Stable disease was achieved in 3 dogs. Mild gastrointestinal toxicity was reported in 3 dogs posttreatment. Thrombocytopenia was the principal toxicity observed 7–14 days after the treatment. Treatments were delayed because of thrombocytopenia.
Conclusions: DTIC, when used alone, is effective in the treatment of dogs with relapsed lymphoma.     

Drug Residues in Serum of Dogs Receiving Anticancer Chemotherapy

Background: The presence of drug residues in blood samples can represent an occupational hazard. However, studies on cytotoxic drug residues in serum of dogs are lacking in veterinary oncology. Objective: To evaluate possible occupational hazards associated with handling of blood samples from dogs receiving oncolytic drugs 7 days after treatment. Animals: Twenty‐seven client‐owned dogs treated for lymphoma or mast cell tumors with vincristine, vinblastine, cyclophosphamide, or doxorubicin. Methods: Prospective, observational study. Serum samples were either taken 7 days after administration of vincristine, cyclophosphamide, doxorubicin (lymphoma), and vinblastine (mast cell tumor), or 1–2 days after the last concurrent oral administration of cyclophosphamide (mast cell tumor). Additionally, serum was collected within 5 minutes of treatment. Measurement of drug residues in serum was performed by liquid chromatography tandem mass spectrometry (LC/MS/MS). Results: In 33 samples collected within 5 minute of treatment, the median serum concentrations were vincristine: 37 μg/L (range: 11–87 μg/L), vinblastine: 13 μg/L (range: 13–35 μg/L), cyclophosphamide: 2,484 μg/L (range: 1,209–2,778 μg/L), doxorubicin: 404 μg/L (range: 234–528 μg/L). In 81 serum samples collected 7 days after treatment vinblastine (7 μg/L) was detected in 1 sample, and cyclophosphamide (7 and 9 μg/L) in 2 samples collected 1–2 days after oral administration of cyclophosphamide. Medications were not detected in any of the other samples. Conclusions and Clinical Importance: Handling of blood samples from dogs receiving oncolytic chemotherapy 7 days after treatment with vincristine, vinblastine, cyclophosphamide, and doxorubicin should not present a health hazard.     

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.     

Acute Reactions in Dogs Treated with Doxorubicin: Increased Frequency with the Use of a Generic Formulation

During a 4-month period, 34 dogs with tumors received a total of 60 doses of a single generic formulation of doxorubicin; 13 acute drug reactions were observed in these 34 dogs, and no acute reactions were observed after replacing the product with the proprietary brand. These reactions were characterized by one or more of the following signs: pruritus; head-shaking; urticaria; erythema of the pinnal, axillary, or inguinal regions; vocalization; vomiting; hyperemic or pale mucous membranes; high heart rate; and high respiratory rate. We propose that a component unique to generic doxorubicin was responsible for the unusually high number of acute drug reactions observed.     

Salivary Cortisol Concentrations in Healthy Dogs and Dogs with Hypercortisolism

Background: Measurement of salivary cortisol is a useful diagnostic test for hypercortisolism (HC) in humans. Objectives: To determine whether measurement of salivary cortisol concentration is a practical alternative to plasma cortisol to diagnose HC, to validate the use of salivary cortisol, and to examine the effect of time of day and sampling location on salivary cortisol. Animals: Thirty healthy dogs and 6 dogs with HC. Methods: Prospective, observational clinical trial including healthy volunteer dogs and dogs newly diagnosed with HC. Salivary and plasma cortisol concentrations were measured with an immunoassay analyzer. Intra‐ and interassay variability, linearity, and correlation between salivary and plasma cortisol concentrations were determined. Results: The required 300 μL of saliva could not be obtained in 88/326 samples from healthy dogs and in 15/30 samples from dogs with HC. The intra‐assay variability for measurement of salivary cortisol was 5–17.7%, the interassay variability 8.5 and 17.3%, and the observed to expected ratio 89–125%. The correlation (r) between salivary and plasma cortisol was 0.98. The time of day and location of collection did not affect salivary cortisol concentrations. Dogs with HC had significantly higher salivary cortisol values than healthy dogs (10.2 ± 7.3 nmol/L versus 1.54 ± 0.97 nmol/L; P < .001). Conclusions and Clinical Importance: The ROCHE Elecsys immunoassay analyzer correctly measured salivary cortisol in dogs. However, a broad clinical application of the method seems limited, because of the large sample volume required.     

Early Tumor Response to Intraarterial or Intravenous Administration of Carboplatin to Treat Naturally Occurring Lower Urinary Tract Carcinoma in Dogs

Background

Survival times and tumor responses associated with malignant neoplasia of the lower urinary tract are poor despite the vast array of current treatments. Therefore, the evaluation of alternative treatments, such as intraarterial administration of chemotherapy (IAC) should be considered.

Objective

To describe a technique for superselective catheterization for IAC and to evaluate initial tumor response by ultrasonography after both IAC and intravenous administration of chemotherapy (IVC).

Animals

Client‐owned dogs with lower urinary tract neoplasia treated with either IVC (n = 15) or IAC (n = 11).

Methods

Retrospective study. An arterial approach via the carotid or femoral artery was utilized to obtain superselective access and administer chemotherapy in the IAC cases. Medical record review was performed, data were recorded, and recorded variables were evaluated statistically.

Results

Intraarterial chemotherapy was successfully administered in all cases. There was a significantly greater decrease in longest unidimensional measurement in the IAC group as compared to the IVC group (P = .013). The IAC group was also significantly more likely to have a tumor response as assessed by modified RECIST guidelines (P = .049). Dogs in the IAC group were significantly less likely to develop anemia (P = .001), lethargy (P = .010) and anorexia (P = .024).

Conclusion and Clinical Importance

This study demonstrated the feasibility and efficacy of performing IAC for lower urinary tract neoplasia. Further investigation is necessary as the follow‐up time was short and the impact on long‐term outcome and survival was not determined.     

Infrared Thermography in Dogs with Mammary Tumors and Healthy Dogs

Background

Infrared thermography is a painless, noninvasive, nonionizing diagnostic imaging exam used in human medicine as an auxiliary tool for breast cancer diagnosis in women.

Hypothesis/Objectives

Define thermographic mean temperatures of healthy mammary glands and compare these temperatures with those of mammary glands with tumors in dogs.

Animals

Fifty client‐owned female dogs were evaluated, including 20 with histopathologically confirmed mammary tumor and 30 clinically healthy (control).

Methods

A randomized study using infrared thermography analyzed each mammary gland of the animals from the control group and mammary glands with tumors from the tumor group, then the thermographic temperatures obtained were compared. Thermographic exam was performed in a temperature‐controlled room with a cooled thermographic camera—Flir E‐40 (Flir Systems^®)

Results

There was significantly a higher temperature in the caudal abdominal and inguinal mammary glands than the other glands in the healthy group (P < .05). Dogs with mammary tumors had significantly higher thermographic temperature compared with unaffected glands regardless of the tumor size and the location (P < .05).

Conclusions and clinical importance

The technique seems to be able to assess for the presence of neoplasia within the mammary tissue in bitches. Further investigation is necessary to determine the impact of this technique when adopted clinically.     

Efficacy of Intravenous Administration of Combined Acid Suppressants in Healthy Dogs

Background

Short‐term intravenous co‐administration of famotidine and pantoprazole is used by some veterinarians to treat gastrointestinal bleeding in critically ill dogs. However, clinical studies have not evaluated the efficacy of combination acid suppressant treatment in dogs.

Hypothesis/Objectives

To compare the effect of intravenous co‐administration of famotidine and pantoprazole to monotherapy with pantoprazole on intragastric pH in dogs. We hypothesized that single agent pantoprazole would be more effective than combination with famotidine.

Animals

Twelve healthy adult colony dogs.

Methods

Randomized, 2‐way crossover design. All dogs received placebo (0.9% saline) for 24 hours followed by 1.0 mg/kg IV q12h pantoprazole or combination treatment with famotidine and pantoprazole for 3 consecutive days. Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 0 of treatment. Mean percentage time (MPT) that intragastric pH was ≥3 and ≥4 were compared between groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.017).

Results

The MPT ± standard deviation intragastric pH was greater than ≥3 and 4 were 79 ± 17% and 68 ± 17% for pantoprazole and 74 ± 19% and 64 ± 23% for combination treatment, respectively. There were no significant differences in MPT intragastric pH was ≥3 and 4 between groups. Pantoprazole administered alone achieved pH goals established for humans with acid‐related disorders.

Conclusions and Clinical Importance

These results suggest that short‐term combination treatment with famotidine and pantoprazole is not superior to pantoprazole alone for increasing intragastric pH in dogs.