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1.
Amputation and chemotherapy are the mainstay of treatment for canine appendicular osteosarcoma (OSA). In vitro studies have demonstrated anti‐tumour activity of pamidronate against canine OSA. The purpose of this study was to assess the safety of adding pamidronate to standard post‐operative carboplatin chemotherapy in 17 dogs with appendicular OSA treated with limb amputation. Median disease‐free interval (DFI) and median survival time (MST) were evaluated as secondary endpoints. Incidence of side effects and treatment outcomes were compared to 14 contemporary control patients treated with carboplatin alone. There were no identified side effects to the pamidronate treatment. The median DFI for the study group was 185 days compared to 172 days for the control group (P = 0.90). The MST of the study group was 311 days compared to 294 days for the control group (P = 0.89). Addition of pamidronate to carboplatin chemotherapy for the treatment of canine appendicular OSA is safe and does not impair efficacy of standard carboplatin treatment.  相似文献   

2.
Despite numerous published studies describing adjuvant chemotherapy for canine appendicular osteosarcoma, there is no consensus as to the optimal chemotherapy protocol. The purpose of this study was to determine whether either of two protocols would be associated with longer disease‐free interval (DFI) in dogs with appendicular osteosarcoma following amputation. Dogs with histologically confirmed appendicular osteosarcoma that were free of gross metastases and underwent amputation were eligible for enrollment. Dogs were randomized to receive either six doses of carboplatin or three doses each of carboplatin and doxorubicin on an alternating schedule. Fifty dogs were included. Dogs receiving carboplatin alone had a significantly longer DFI (425 versus 135 days) than dogs receiving alternating carboplatin and doxorubicin (P = 0.04). Toxicity was similar between groups. These results suggest that six doses of carboplatin may be associated superior DFI when compared to six total doses of carboplatin and doxorubicin.  相似文献   

3.
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   

4.
Objective To evaluate the safety and efficacy of a novel doxorubicin and carboplatin chemotherapy protocol for the treatment of dogs with appendicular osteosarcoma following limb amputation. Design Retrospective study. Procedure Dogs diagnosed with appendicular osteosarcoma, with no evidence of metastatic disease, treated with amputation and adjuvant chemotherapy consisting of two doses of doxorubicin given 14 days apart, followed by four doses of carboplatin at 3‐weekly intervals between September 2003 and December 2009 were identified from the medical records of Perth Veterinary Oncology. Haematological and gastrointestinal toxicities were assessed based on information in the medical records and recorded complete blood count results. The efficacy of the protocol was assessed by determining the median disease‐free interval (DFI) and overall survival time (OST) using the Kaplan‐Meier product‐limit method. Results In total, 33 dogs met the inclusion criteria. The median DFI was 231.5 days and the median OST was 247 days. With regard to haematological toxicity, 56% of dogs had a grade 1–2 neutropenia recorded as their highest marrow toxicity and 9% of dogs experienced a grade 3–4 neutropenia, all subsequent to doxorubicin administration. The highest gastrointestinal toxicity was grade 1–2 in 15 dogs (47%) and 5 dogs (16%) experienced grade 3–4 gastrointestinal toxicity. Conclusion This chemotherapy protocol did not result in a longer time to disease recurrence or OST in this population of dogs. Dual‐agent protocols have failed to improve survival times and therefore we conclude that a single‐agent protocol using carboplatin may be equally effective with less toxicity.  相似文献   

5.
OBJECTIVE:To evaluate the efficacy and toxicity of an alternating carboplatin and doxorubicin chemotherapy protocol in dogs with putative microscopic metastases after amputation for appendicular osteosarcoma and assess patient-, tumor-, and treatment-related factors for associations with prognosis. DESIGN: Retrospective case series. ANIMALS: 50 client-owned dogs. PROCEDURES: Records of dogs that underwent amputation for appendicular osteosarcoma and received an alternating carboplatin and doxorubicin chemotherapy protocol were reviewed. Dogs had full staging and were free of detectable metastases prior to chemotherapy. Data on disease-free interval (DFI), survival time, and toxicoses were retrieved from medical records and owner or referring veterinarian communications. RESULTS: Median DFI was 202 days. Median survival time was 258 days. Twenty-nine (58%) dogs completed the protocol as planned, and the rest were withdrawn typically because of metastases or toxicoses. Grade 3 or 4 myelosuppression was reported in 9 of 50 (18%) dogs and grade 3 or 4 gastrointestinal toxicosis in 6 of 50 (12%) dogs. There were no chemotherapy-related fatalities. Univariate factors associated with significant improvement in DFI included tumor location (radius), receiving doxorubicin as the first drug, starting chemotherapy more than 14 days after amputation, and no rib lesions on preamputation bone scans. Multivariate factors associated with a significant improvement in survival time were tumor location (radius) and completing chemotherapy. CONCLUSIONS AND CLINICAL RELEVANCE: Alternating administration of carboplatin and doxorubicin resulted in DFI and survival time similar to those reported for single-agent protocols. Clients should be counseled regarding the likelihood of toxicoses. Relevance of sequence and timing of starting chemotherapy should be further evaluated.  相似文献   

6.
Thirty-six dogs underwent pulmonary metastatectomy for osteosarcoma. All patients had been treated for histologically confirmed osteosarcoma of the appendicular skeleton. Treatment for the primary tumor consisted of amputation or a limb sparing procedure in conjunction with adjuvant chemotherapy, local radiation therapy, or both.
Significant factors in determining prognosis included the disease-free interval (DFI) between treatment of the primary tumor and development of pulmonary metastases and the number of metastatic nodules present at surgery. Dogs that developed pulmonary metastases 300 days or more after diagnosis of the primary tumor had a median DFI of 128 days after metastatectomy. Dogs that developed pulmonary metastases fewer than 300 days after diagnosis had a median DFI of 58 days. Dogs with one or two metastatic nodules removed had a median DFI of 95 days, whereas dogs with three or more nodules removed had a median DFI of 53 days. The results of this study indicate that prognostic variables exist for dogs with metastatic pulmonary osteosarcoma and can help predict survival after metastatectomy. These variables are similar to the prognostic variables that have been determined for human patients undergoing pulmonary metastatectomy because of osteosarcoma. Though a controversial procedure, pulmonary metastatectomy seems to be a valid treatment option for selected dogs with metastatic pulmonary osteosarcoma.  相似文献   

7.
Background: Identification of biomarkers that predict outcomes in dogs with osteosarcoma (OSA) would be valuable to veterinarians and owners. Leukocyte numbers in peripheral blood are associated with outcomes in some types of cancer in humans. Hypothesis/Objectives: We hypothesized that increased numbers of monocytes would be associated with reduced disease‐free interval (DFI) in dogs with OSA. Animals: Medical data from 69 dogs with appendicular OSA treated with amputation and chemotherapy were selected for study. Methods: Retrospective study. Statistical associations were assessed by univariate and multivariate analysis. Information about DFI and leukogram values, tumor location, and serum alkaline phosphatase was abstracted from the medical record. Results: Higher numbers of circulating monocytes (>0.4 × 103 cells/μL) and lymphocytes (>1.0 × 103 cells/μL) before treatment were found to be significantly (P < .05) associated with shorter DFI in dogs with OSA. Other parameters associated with poor outcomes were increased alkaline phosphatase, primary tumor location, and age. Conclusion and Clinical Importance: These results indicated that pretreatment evaluation of monocyte and lymphocyte counts provided prognostic information for dogs with appendicular OSA. Notably, most animals in this study had monocyte counts within the normal reference range, indicating that variations within the reference range of leukocyte values might also have prognostic significance.  相似文献   

8.
Objective: To evaluate clinical presentation of pathologic fractures associated with suspected or confirmed osteosarcoma in dogs and to assess treatment and survival times. Study design: Case series. Animals: Dogs (n=25) appendicular pathologic fracture. Methods: Medical records (January 1997–May 2008) of dogs with pathologic fracture associated with a suspected or confirmed osteosarcoma were reviewed. Dogs were included if they had radiographic evidence of a pathologic fracture and a presumptive or definitive diagnosis of osteosarcoma. Radiographic details, histopathology, and/or cytology findings were recorded. Overall median survival time (MST) and MST of treated dogs were calculated. Age, sex, breed, and other concurrent treatment were evaluated. Results: Rottweilers, Irish Wolfhounds, and Greyhounds were the most common breeds represented. Most dogs had minor trauma and 60% had lameness preceding the fracture. Most commonly, fractures were nondisplaced with minimal comminution. None of the dogs had radiographic evidence of pulmonary metastases at admission. Immediate (13 dogs; 52%) and delayed (4; 16%) euthanasia were performed. One dog was not treated and died 90 days after diagnosis. Three dogs (12%) were treated by amputation alone, 1 (4%) with amputation and chemotherapy, and 3 (12%) with internal fixation using an interlocking nail. Overall MST was 1 day (range, 0–623 days) and MST of treated dogs was 406.5 days. Histologic confirmation of osteosarcoma was available in all treated dogs and 6 euthanatized dogs. Conclusions: Treatment of pathologic fracture associated with presumptive osteosarcoma should be considered as an option to amputation or euthanasia if owners desire other options.  相似文献   

9.
Sixteen dogs, given adjuvant cisplatin chemotherapy after amputation for osteogenic sarcoma of the appendicular skeleton, had a median survival time of 413 days. Ten dogs (62%) were alive 1 year after amputation. Dogs were given cisplatin at a dosage of 50 mg/m2 of body surface every 4 weeks for a total of 6 cisplatin treatments, or until metastatic disease was detected. Cisplatin chemotherapy was well-tolerated by most dogs, with only 1 dog developing serious gastrointestinal toxicosis, requiring hospitalization. Results of this study support other investigators' findings that when a cisplatin chemotherapy-based protocol is administered, survival times after amputation can be prolonged for dogs with osteogenic sarcoma.  相似文献   

10.
Objective— To characterize biologic behavior, clinical outcome, and effect of histologic grade on prognosis for dogs with appendicular chondrosarcoma treated by amputation alone. Study Design— Case series. Animals— Dogs (n=25) with appendicular chondrosarcoma. Methods— Medical records were searched to identify dogs with appendicular chondrosarcoma treated by limb amputation alone. Information recorded included signalment, anatomic location, radiographic appearance, and development of metastasis. Histopathologic diagnosis was confirmed and graded (1, 2, or 3). Survival curves were generated by the Kaplan–Meier method and the association between covariates (gender, age, weight, and tumor grade) and survival were evaluated using the univariate proportional hazards model. Results— Histopathology slides were available for 25 dogs. Rates of pulmonary metastasis were as follows: grade 1–0%, grade 2–31%, and grade 3–50%. Overall median survival time (MST) was 979 days. Age, weight, and sex were not significantly associated with survival (P=.16; .33; and .31, respectively). Survival was significantly associated with tumor grade (P=.008), with dogs with tumor grade of 1, 2, and 3 having MSTs of 6, 2.7, and 0.9 years, respectively. Conclusion— Canine appendicular chondrosarcoma can be treated effectively with amputation alone. Low to intermediate grade chondrosarcoma has a good prognosis, whereas high‐grade tumors appear to behave aggressively. Clinical Relevance— The overall prognosis for appendicular chondrosarcoma is better than that of appendicular osteosarcoma treated by amputation alone or in combination with chemotherapy.  相似文献   

11.
Enumeration of circulating tumour cells (CTC) has shown promise for prognostication and guidance of therapeutic decisions in human cancers. The objective of this study was to enumerate CTC over time in dogs with naturally occurring osteosarcoma (OSA), and to determine correlation with patient outcome. Twenty-six dogs with OSA and no evidence of metastatic disease at the time of amputation were enrolled. Dogs were assessed for lung metastases and CTC prior to and following amputation, and at each chemotherapy visit. Twenty-one dogs completed the study. Nineteen dogs were euthanized and two were alive and free of metastases. Overall survival time ranged from 88 to 1058 days (median survival time (MST) 374 days). Increased serum alkaline phosphatase activity, advanced age, and higher body weight were significantly associated with lower MST. Dogs with OSA had a mean of 356 (0 to 4443) CTC/106 leukocytes. In 12 of 15 dogs that developed radiographic evidence of metastasis, a pre-metastatic CTC spike was retrospectively detectable on average 36.5 (1–100 days) days prior to metastasis and was associated with significantly shorter MST (301 ± 64 vs. 626 ± 55 days; p = .0107). In a multivariable analysis, dogs with a CTC spike were 10× more likely to die compared with those without. These results suggest that a spike in CTC frequency precedes detection of metastasis in dogs with OSA and is associated with shorter survival. More frequent enumeration of CTC in a larger cohort of dogs with OSA may be warranted.  相似文献   

12.
Objective: To report outcome in dogs after internal fixation of a sarcoma‐related pathologic fracture of the appendicular skeleton. Study Design: Multi‐institutional case series. Animals: Dogs (n=16). Methods: Medical records of participating VSSO members were reviewed for dogs with pathologic fracture associated with a confirmed bone sarcoma of the appendicular skeleton repaired by external or internal fixation. Dogs were included if they had a histological diagnosis of osteosarcoma or sarcoma and excluded if they had radiation before fracture. Data collected were analyzed for signalment, fracture location, staging performed, method of fracture fixation, histopathology, adjunctive treatment and outcome. Results: Signalment and fracture location of 16 dogs that met the inclusion criteria was similar to dogs with appendicular OSA without fracture. One of 14 dogs had pulmonary metastasis and 3 of 5 dogs had bone metastasis. Bone plate or interlocking nail were used for repair in 12 dogs. Limb use immediately after surgery in 13 dogs was good (4), weight‐bearing but lame (7) and non‐weight bearing (2). Adjunctive therapy was administered in 5 dogs (chemotherapy, 3; radiation, 4; pamidronate, 3). Survival time ranged from 18 to 897 days; median survival was 166 days. Conclusions: Repair of pathologic fracture can result in palliation and prolonged survival.  相似文献   

13.
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.  相似文献   

14.
Appendicular osteosarcoma (OSA) remains a prevalent musculoskeletal cancer in dogs and definitive local control followed by adjuvant cytotoxic chemotherapy is considered the gold standard approach. Several studies support surgical limb salvage as a means of local control with similar outcomes compared with limb amputation. Complications are well described for limb salvage but little is known of dogs that undergo secondary amputation as a result of complications and outcomes specific to this group. A retrospective analysis of dogs in an institutional primary bone tumour registry was performed to identify dogs diagnosed with histologically confirmed OSA treated with surgical limb salvage with a technique that required an implant to reconstruct the osseous defect. A total of 192 dogs were identified with 31 dogs undergoing secondary amputation representing a limb preservation rate of 84%. A total of 111 dogs were analysed: 31 secondary amputation cases and 80 controls were selected for comparison. The most common reasons for secondary amputation were local recurrence (LR) and surgical site infection (SSI), with odds ratios of 3.6 and 1.7, respectively. Dogs that underwent secondary amputation had a significantly (P = .05) longer median disease specific survival time (ST) (604 days) compared with the control group (385 days). Dogs lived for a median of 205 days beyond secondary amputation and 97% had good functional outcome. Significant independent factors that positively influenced ST were secondary amputation, moderate SSI, severe SSI and age.  相似文献   

15.
OBJECTIVE: To compare surgical and oncologic outcome in dogs with osteosarcoma (OSA) of the distal aspect of the radius treated with limb-sparing surgery, using either a cortical allograft or endoprosthesis, and postoperative chemotherapy; and to evaluate predictive factors for outcome. STUDY DESIGN: Prospective cohort study. ANIMALS: Dogs (n = 20) with spontaneous, non-metastatic OSA of the distal aspect of the radius. METHODS: Dogs were prospectively randomized for limb-sparing surgery with either a cortical allograft (n = 10) or endoprosthesis (10) and full-course adjuvant chemotherapy using single or dual agent protocols of cisplatin, carboplatin, and/or doxorubicin. Surgical (intraoperative findings, postoperative infection, construct failure) and oncologic (local tumor recurrence, metastasis, survival) outcomes were compared. The influence of intraoperative and postoperative variables on surgical and oncologic outcome were evaluated. RESULTS: No clinically significant differences in surgical and oncologic outcome were detected between groups. The percentage of radius replaced by the implant was significantly greater in the endoprosthesis group (60.9% compared with 48.6%, P = .008). Median survival time (MST) for dogs with construct failure, regardless of implant type, was 685 days and significantly greater than MST of dogs without construct failure (322 days, P = .042; hazard ratio [HR] 16.82). Median metastasis-free interval and MST (685 days versus 289 days; P = .034, HR 24.58) were significantly greater in dogs with postoperative infection. Disease-free and overall limb-salvage rates were 70% and 85%, respectively. Overall MST was 430 days. CONCLUSIONS: For dogs with OSA of the distal aspect of the radius, a cortical allograft or endoprosthesis can be used for limb-sparing surgery. Construct failure and postoperative infection significantly improve survival time regardless of implant type. CLINICAL RELEVANCE: An endoprosthesis is an attractive alternative to cortical allografts for limb-salvage of the distal aspect of the radius in dogs because surgical and oncologic outcomes are similar, but the endoprosthesis is an immediately available off-the-shelf implant which is not complicated by the bone harvesting and banking requirements associated with cortical allografts. Mechanisms whereby postoperative infection improves survival time requires further investigation and, if elucidated, may provide the opportunity to improve the outcome of dogs and humans with OSA.  相似文献   

16.
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17.
Canine appendicular osteosarcoma (OSA) is a commonly diagnosed cancer that is capable of inducing pathologic bone remodeling. Investigating surrogate indices of bone metabolism may contribute to the diagnostic and therapeutic management of bone malignancies in companion animals. This study evaluated the excretion of N-terminal telopeptide (NTx), a marker of bone resorption that is detected in urine. Sixty-three dogs with appendicular OSA were compared with 29 age-matched healthy dogs. Dogs with appendicular OSA had significantly higher baseline urine NTx excretion than healthy controls (P < .0001). In 17 dogs with OSA treated with either amputation or standardized palliative therapies, significant reductions in urine NTx excretion were observed, suggesting that excessive bone resorption in dogs with OSA may be linked with focal skeletal osteolysis or its consequences. To identify any relationship between indicators of pathologic bone turnover, baseline urine NTx excretion was correlated with serum bone alkaline phosphatase (bALP) or radiographic tumor lengths at diagnosis. No significant correlations were identified between baseline urine NTx excretion and either bALP or tumor length. The findings from this study suggest that high urinary NTx excretion may support the diagnosis of focal skeletal osteolysis in dogs, and reductions in urine NTx excretion after treatment may reflect elimination or minimization of pathologic bone resorption.  相似文献   

18.
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19.
Thirty-two dogs with appendicular osteosarcoma treated by amputation or limb sparing had adjuvant chemotherapy of alternating doses of carboplatin (300 mg/m2 IV) and doxorubicin (30 mg/m2 IV) every 21 days for a total of 3 cycles. Efficacy, toxicity, and previously identified prognostic factors for osteosarcoma were evaluated. The median progression free survival was 227 days (range 180-274), and the median overall survival was 320 days (range 153-487). The 1-year survival rate was 48%, and the 2-year survival rate was 18%. Age, sex, surgical procedure, and alkaline phosphatase activity above the reference ranges were not prognostic for survival. There was minimal toxicity associated with the chemotherapy. This protocol could be useful for the adjuvant treatment of appendicular osteosarcoma of dogs.  相似文献   

20.
Reported post‐surgery 1‐year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan‐4 (hCSPG4)‐encoded plasmid in 23 dogs with resected II/III‐staged CSPG4‐positive oral cMM compared with 19 dogs with resected only II/III‐staged CSPG4‐positive oral cMM. Vaccination resulted in 6‐, 12‐, 18‐ and 24‐month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78–1694, 8 of 23 dogs alive] and 6‐, 12‐, 18‐ and 24‐month disease‐free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50–1694). Non‐vaccinated dogs showed 6‐, 12‐, 18‐ and 24‐month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75–1507, 1 of 19 dogs alive) and 6‐, 12‐, 18‐ and 24‐month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38–1250). Overall survival and DFI of vaccinated dogs was longer in those <20 kg. In vaccinated and non‐vaccinated dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively.  相似文献   

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