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1.
Twenty-five dogs with malignant lymphoma refractory to chemotherapy were treated with actinomycin D at a median dose of 0.7 mg/m2 (range, 0.5 to 0.9 mg/m2) every 3 weeks. The dogs treated had received between 2 and 8 chemotherapeutic agents (median 7), for a median of 266 days before being treated with actinomycin D. For 23 of the 25 dogs, previous chemotherapy included doxorubicin. No dog responded to actinomycin D chemotherapy.  相似文献   

2.
Treatment of Tumor-Bearing Dogs With Actinomycin D   总被引：2，自引：1，他引：1  
Fifty dogs with advanced malignancies were treated with actinomycin D at doses ranging from 0.5 to 1.1 mg/m2 every 3 weeks. The greatest number of responses was noted in dogs with lymphoma, including dogs that had received prior chemotherapy. Other responding tumor types included anal sac adenocarcinoma, perianal adenocarcinoma, squamous cell carcinoma, thyroid carcinoma, and transitional cell carcinoma. The median time to maximum response for dogs with lymphoma was 7 days, with a median duration of 42 days. Gastrointestinal toxicity was the most frequently observed side effect. A dose of 0.6 to 0.7 mg/m2 appears to be appropriate for treating various malignancies in dogs.  相似文献   

3.
The purpose of this study was to evaluate the efficacy and toxicity of an intensified dose protocol with no maintenance phase for the treatment of canine lymphoma. Forty-nine dogs all weighing more than 15 kg were entered. Dogs were staged and treated with a modified version of the University of Wisconsin (UW)-Madison protocol for lymphoma. Modifications included increased dosages of cyclophosphamide (250 mg/m2 compared to 200 mg/m2) and doxorubicin (37.5 mg/m2 compared to 30 mg/m2), with no crossover to chlorambucil or methotrexate. After 25 weeks on protocol (17 treatments), therapy was discontinued and dogs were monitored for relapse on a monthly basis. Disease-free interval (DFI) and overall survival were compared to 55 historical controls treated with the UW-Madison protocol. The 2 groups were comparable with respect to age, sex, breed, stage, presence of hypercalcemia, and CD3 status; a trend toward more substage b dogs was present in the high-dose group ( P = .076). When comparing response rate, DFI, death due to disease, and death due to treatment-related toxicity, more dogs were dead due to toxicity ( P < .001; odds ratio = 8.8) in the high-dose group. Overall survival between the high-dose and control groups did not differ significantly ( P = .55) at 270 and 318 days, respectively. The intensified dose protocol is an option for owners who are willing to risk higher toxicity for a shorter protocol with no statistical difference in survival from the UW-Madison protocol.  相似文献   

4.
Fourteen dogs with histologically-confirmed transitional cell carcinoma (TCC) of the urinary bladder were treated with 300 mg/m2 carboplatin every 3 weeks. Response to therapy was assessed with abdominal radiography, double contrast cystography, urinary bladder ultrasonography and thoracic radiography before therapy and at 6–week intervals during therapy. Dogs were monitored for hematologic toxicity with a CBC and platelet count performed immediately before and 10 to 14 days after carboplatin treatment. Tumor responses included progressive disease in 11 dogs and stable disease in 1 dog. Two dogs were euthanized due to carboplatin toxicity before assessment of tumor response. Toxicity included thrombocytopenia with or without neutropenia in 7 dogs and gastrointestinal toxicity in 6 dogs. Carboplatin therapy was not beneficial in the treatment of TCC in the 14 dogs in this study.  相似文献   

5.
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.  相似文献   

6.
Nineteen dogs with histologically confirmed soft tissue sarcomas of the extremities were treated with a combination of marginal surgery and intra-operative chemotherapy in the form of cisplatin in a biodegradable implant delivery system (Atrigel®; Atrix Laboratories, Fort Collins, Co, USA). None of the dogs had evidence of metastasis at time of treatment. The median dose of cisplatin was 52.1 mg/m2 (mean 55.4 mg/m2, range 18.5–108.6 mg/m2). Wound complications were noted in 16 dogs (84.2%). Median follow-up time was 874 days (mean 777 days, range 125–1463 days). Nine dogs (47.3%) were alive at the time of analysis. Local recurrence occurred in three dogs (16.6%). The time to recurrence was 214, 264 and 874 days.  相似文献   

7.
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.  相似文献   

8.
Systemic Toxicity Associated With Doxorubicin Administration in Cats   总被引：2，自引：0，他引：2  
The systemic toxicity of doxorubicin, 30 mg/m2 body surface area (BSA) every 21 days to a cumulative dose of 300 mg/m2, was evaluated in six cats. Appetite, body weight, and the presence of vomiting and/or diarrhea were monitored throughout the study. Renal function was monitored by measuring serum blood urea nitrogen (BUN) and creatinine concentrations, urine specific gravity, and creatinine clearance before each treatment. Electrocardiograms and echocardiograms were also done before each treatment. The cats were killed 3 weeks after the last treatment, and complete necropsies were performed. Partial or complete anorexia occurred in all cats with significant weight loss occurring after a cumulative doxorubicin dose of 150 mg/m2 BSA. Mild vomiting and diarrhea that required no treatment also occurred sporadically in all cats. Echocardiographic changes consistent with doxorubicin-induced cardiomyopa-thy occurred in four cats after cumulative doses of 170 to 240 mg/m2 BSA. Clinical heart disease and electrocardiographic changes were not observed. Subsequent histological examination revealed myocyte vacuolization and myocytolysis in all six hearts. Renal dysfunction, characterized by increasing azotemia with progressively more dilute urine, was detected in two cats. Mean creatinine clearance values also decreased significantly throughout the study. At necropsy, all cats had histological evidence of renal disease. (Journal of Veterinary Internal Medicine 1993; 7:309–317. Copyright © 1993 by the American College of Veterinary Internal Medicine.)  相似文献   

9.
Many chemotherapeutic regimens will induce remission in dogs with lymphoma, but almost all dogs suffer relapse. Mitoxantrone was selected for evaluation as single-agent chemotherapy for relapsing canine lymphoma based on its use in humans undergoing salvage chemotherapy for non-Hodgkin's lymphoma and its tumoricidal effect against canine lymphoma. Dogs entered into study had multicentric lymphoma, and all had been treated solely with a standard combination chemotherapy protocol. At 1st relapse, all dogs were again staged and underwent lymph node biopsy. Mitoxantrone was administered IV at 6 mg/m2 every 21 days. Dogs were evaluated for lymphadenopathy before each dose of mitoxantrone. Fifteen dogs were entered into study. The average age (±SEM) of the dogs studied was 7.7 ± 0.91 years, and most dogs were large (mean ± SEM weight, 24.44 ± 2.15 kg). Twelve dogs (80%) had B-cell lymphoma, and 3 had T-cell lymphoma. Dogs were staged IV (n = 12) or V (n = 3). The median duration of chemotherapy before entry into the study was 98 days. Overall median duration of response after mitoxantrone chemotherapy was 21 days. Complete responses were attained in 7 of 15 dogs (47%) with a median response duration of 84 days. Nine of 15 (60%) dogs attained a complete remission with additional chemotherapy after failing mitoxantrone chemotherapy. Mild toxicities were observed after mitoxantrone administration. No adverse reactions were observed during mitoxantrone infusions. The results of this study demonstrate that mitoxantrone, as a single agent, has limited value for dogs with lymphoma at 1st relapse after conventional multidrug chemotherapy.  相似文献   

10.
Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights (40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m2. Neutropenia was the dose-limiting toxicity in this study. J Vet Intern Med 1996;10:76–81. Copyright © 1996 by the American College of Veterinary Internal Medicine .  相似文献   

11.
RADIATION AND CISPLATIN FOR TREATMENT OF CANINE URINARY BLADDER CARCINOMA   总被引：1，自引：0，他引：1  
Two cases of canine urinary bladder carcinoma were treated with combined radiation and cisplatin. Total radiation dose was 4400 cGy for one dog and 4800 cCy for the other. Cobalt 60 radiation was fractioned using 400 cGy per fraction. Cisplatin was administered intraarterially at a dose of 50 mg/m2 divided equally six to seven hours before the first three radiation fractions. Cisplatin was administered before the last three radiation fractions at the same dose and time, but was infused intravenously. Objective evaluation using double contrast cystograms revealed reduction in tumor size in both dogs. The therapy was well-tolerated with minimal side effects.  相似文献   

12.
The effects of buprenorphine in combination with acepromazine, midazolam or medetomidine were compared in dogs. Induction and recovery times, heart rate, respiratory rate and body temperature were measured. Posture, reaction to noise, analgesia and muscle relaxation were assessed and a global score of "sedation-analgesia" was calculated. There were 3 groups of 4 animals: group 1 received 0.1 mg.kg-1 acepromazine IM and 20 minutes later, 10 g.kg-1 buprenorphine IV; group 2 received 1 mg.kg-1 midazolam IV simultaneously with 10 ig.kg-1 buprenorphine IV and group 3 received 1 mg/m2 body surface area medetomidine IM and 20 minutes later, 10 Hg.kg-1 buprenorphine IV. Only one dog given acepromazine and buprenorphine reached a "sedation-analgesia" stage, denned as the inability to stand together with the absence of reaction to stimulation, including pain. Animals in this group showed a decrease in respiratory rate and in body temperature. None of the dogs given midazolam and buprenorphine became sedated or showed signs of analgesia. Following this combination, the dogs were excited and showed dysphoric reactions which disappeared within 20 minutes.
All of the dogs given medetomidine and buprenorphine showed good sedation and analgesia lasting more than 20 minutes. This drug combination produced a decrease in heart and respiratory rates and body temperature.  相似文献   

13.
The effects of metaraminol bitartrate on intraocular pressure (IOP) were studied in dogs anesthetized with halothane. Forty-five healthy, adult, mixed-breed dogs, of both sexes, were divided into three groups of 15 dogs each (GI, GII and GIII) and maintained under general anesthesia with halothane after tranquilization with levomepromazine and induction with thiopental. Saline (0.9%) was administered intravenously (IV) to GI through continuous infusion, at a velocity of 0.125 mL kg−1 min−1. GII and GIII received metaraminol 0.004% IV, at a dose of 5 μg kg−1 min−1, at 0.125 mL kg−1 min−1 and at a dose of 2 μg kg−1 min−1, at 0.06 mL kg−1 min−1, respectively. IOP was measured by applanation tonometry (Tono-Pen) before and during anesthesia. Results showed that IOP decreased in GI, increased in GII, and remained at basal levels in GIII. Continuous infusion of metaraminol at 2 μg kg min−1 maintained IOP at pretest levels, while infusion at 5 μg kg−1 min−1 produced an elevation of IOP.  相似文献   

14.
Purpose  To determine the effects of a standardized intravenous dose of an α-2 agonist (Domitor®, Orion Pharma, distributed by Pfizer Animal Health, Exton, PA) on the electroretinogram (ERG) response in normal dogs.
Methods  Twenty-five normal dogs were used to collect ERG responses including a- and b-wave implicit times (IT) and amplitudes (AMP) before and after administration of medetomidine. Dogs were dark adapted for 20 min and ERGs were obtained using the HMsERG (RetVetCorp Inc., Columbia, MO). The QuickRetCheck protocol (Narfström) was employed to provide the following flash intensities: 10 mcd s/m2, 3 cd s/m2, and 10 cd s/m2. ERGs were repeated after 375 µg/m2 of medetomidine intravenously. Statistical analysis of the difference between the responses before and after medetomidine at all flash intensities was performed using a mixed effects model for anova .
Results  The P value for the effect of medetomidine on each of the ERG responses was < 0.01. The estimates of the effect of medetomidine were (+)1.35 ms, (–)23 µV, (+)3.16 ms, and (–)47 µV for the a-wave IT, a-wave AMP, b-wave IT, and the b-wave AMP, respectively.
Conclusions  Medetomidine significantly prolongs the implicit time and lowers the amplitude response of both the a- and b-waves in normal dogs at all flash intensities examined. Clinically, however, medetomidine only minimally affects the retinal responses and is a viable choice for use in dog ERGs.  相似文献   

15.
Background: Dogs that harbor the naturally occurring ABCB1-1Δ polymorphism experience increased susceptibility to avermectin-induced neurological toxicosis as a result of deficient P-glycoprotein function. Whether or not the ABCB1-1Δ polymorphism affects susceptibility to toxicity of other P-glycoprotein substrate drugs has not been studied.
Hypothesis: Dogs that possess the ABCB1-1Δ mutation are more likely to develop hematologic toxicity associated with vincristine than ABCB1 wild-type dogs.
Animals: Thirty-four dogs diagnosed with lymphoma were included in this study.
Methods: Cheek swab samples were obtained from dogs diagnosed with lymphoma that were to be treated with vincristine. DNA was extracted from cheek swabs and the ABCB1 genotype was determined. Hematologic adverse drug reactions were recorded for each dog and graded according to the Veterinary Comparative Oncology Group's criteria for adverse event reporting (Consensus Document). In order to avoid possible bias, ABCB1 genotype results for a particular patient were not disclosed to oncologists until an initial adverse event report had been submitted.
Results: Dogs heterozygous or homozygous for the ABCB1-1Δ mutation were significantly more likely to develop hematologic toxicity, specifically neutropenia ( P = .0005) and thrombocytopenia ( P = .0001), after treatment with vincristine than ABCB1 wild-type dogs.
Conclusions and Clinical Implications: At currently recommended dosages (0.5–0.7 mg/M2), vincristine is likely to cause hematologic toxicity in dogs with the ABCB1-1Δ mutation, resulting in treatment delays and unacceptable morbidity and mortality. Assessing the ABCB1-1Δ genotype before vincristine administration and decreasing the dosage may prevent toxicity and treatment delays resulting from neutropenia or thrombocytopenia.  相似文献   

16.
Objective  To investigate the effects of a low-dose constant rate infusion (LCRI; 50 μg kg−1 minute−1) and high-dose CRI (HCRI; 200 μg kg−1 minute−1) lidocaine on arterial blood pressure and on the minimum alveolar concentration (MAC) of sevoflurane (Sevo), in dogs.
Study design  Prospective, randomized experimental design.
Animals  Eight healthy adult spayed female dogs, weighing 16.0 ± 2.1 kg.
Methods  Each dog was anesthetized with sevoflurane in oxygen and mechanically ventilated, on three separate occasions 7 days apart. Following a 40-minute equilibration period, a 0.1-mL kg−1 saline loading dose or lidocaine (2 mg kg−1 intravenously) was administered over 3 minutes, followed by saline CRI or lidocaine LCRI or HCRI. The sevoflurane MAC was determined using a tail clamp. Heart rate (HR), blood pressure and plasma concentration of lidocaine were measured. All values are expressed as mean ± SD.
Results  The MAC of Sevo was 2.30 ± 0.19%. The LCRI reduced MAC by 15% to 1.95 ± 0.23% and HCRI by 37% to 1.45 ± 0.21%. Diastolic and mean pressure increased with HCRI. Lidocaine plasma concentration was 0.84 ± 0.18 for LCRI and 1.89 ± 0.37 μg mL−1 for HCRI. Seventy-five percent of HCRI dogs vomited during recovery.
Conclusion and clinical relevance  Lidocaine infusions dose dependently decreased the MAC of Sevo, did not induce clinically significant changes in HR or arterial blood pressure, but vomiting was common during recovery in HCRI.  相似文献   

17.
The neurons in bilateral superior cervical ganglia (SCG) innervating the chick pineal gland were labelled by using the technique of retrograde axonal labelling with cholera toxin B subunit linked to horseradish peroxidase (CTB-HRP). To our results, perikarya of these sympathetic neurons distributed from rostral to caudal in the SCG, and mainly localized in the opposite side of the paravertebral trunk. The fibres of these neurons were collected by the cephalic carotid nerve. According to the sizes of somal area and dendritic field, these sympathetic neurons projecting to the pineal gland were classified into four major groups: group I cells (52.4%) with a small somal area (303.5 μm2 on average) and narrow dendritic field (3767.8 μm2 on average), group II cells (39.0%) with a middle-sized somal area (473.3 μm2) and middle-sized dendritic field (7522.2 μm2), group III cells (6.4%) with a middle-sized somal area (473.4 μm2) and wide dendritic field (13 104.4 μm2), and group IV cells (2.2%) with a large somal area (940.7 μm2) and wide dendritic field (14 553.2 μm2). Of these pineal projecting neurons, most took on a lesser dendritic field. The neurons with small or middle-sized dendritic field from group I and II were about 91.4% of the total neurons labelled with CTB-HRP, and the neurons with wide dendritic field from group III and IV were less with 8.6%.  相似文献   

18.
Vincristine Therapy for Mast Cell Tumors in Dogs   总被引：1，自引：0，他引：1  
Twenty-seven dogs with naturally occurring mast cell tumors were treated with weekly IV injections of vincristine (0.75 mg/m2) for 4 treatments. Two dogs (7%) had a partial response. Nine dogs (32%) had treatment stopped prematurely because of toxicity or a perceived deterioration in their quality of life. We conclude that vincristine is ineffective as a sole treatment for measurable mast cell tumors in dogs and produces an undesirable number of adverse reactions.  相似文献   

19.
A 9-year-old female spayed Boxer dog presented with variably sized, firm, black, raised, exudative subcutaneous masses on her head, neck and trunk, that tended to fluctuate in size and frequently ulcerate. Skin biopsy showed that the dermis was expanded by a densely cellular mass of proliferative capillaries distended with large pleomorphic neoplastic round cells mixed with fibrin and erythrocytes. Intravascular lymphoma was diagnosed and immunostains were compatible with a CD8+ T lymphocyte histogenesis (CD3+/CD79a−/TCRαβ+/CD8α+). Post-mortem examination, four months after diagnosis, revealed neoplastic T-cells within meningeal arteries. We are unaware of other reports of a cutaneous presentation and ante-mortem diagnosis of intravascular lymphoma in the dog. Additionally, this vasoproliferative form of intravascular lymphoma has not been previously described in dogs.  相似文献   

20.
Rabacfosadine (RAB), a novel double prodrug of the acyclic nucleotide phosphonate PMEG, preferentially targets neoplastic lymphocytes with reduced off target toxicity. Historical studies have suggested that every 21‐day dosing is effective with acceptable toxicity. The purpose of this study was to evaluate RAB’s safety and efficacy at 2 different doses every 21 days in dogs with relapsed B‐cell lymphoma. Dogs that had failed 1 doxorubicin‐based chemotherapy protocol were eligible for inclusion in this prospective trial. Once enrolled, dogs were randomized to receive RAB at either 0.82 mg/kg or 1.0 mg/kg as a 30‐minute IV infusion every 21 days for up to 5 treatments. Response assessment and adverse event (AE) evaluation were performed every 21 days via VCOG criteria. Fifty dogs were enrolled, with 16 treated at 0.82 mg/kg and 34 treated at 1.0 mg/kg. The overall response rate was 74%, with 45% of dogs experiencing a complete response (CR). The median progression free intervals (PFIs) were 108 days, 172 days and 203 days for all dogs, all responders, and all CRs, respectively. Response rates and PFIs were similar in both treatment groups. The incidence of AEs, dose delays, dose reductions and withdrawals were not statistically different between the 2 groups. The AEs observed were similar to those previously reported and included hematologic, gastrointestinal, dermatologic and pulmonary AEs. One dog had grade 5 pulmonary fibrosis; otherwise, AEs resolved with supportive treatment. Rabacfosadine is a generally well tolerated, effective chemotherapy option for dogs with relapsed B‐cell lymphoma.  相似文献   

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