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1.
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   

2.
Canine Osteosarcoma   总被引:4,自引:0,他引:4  
Osteosarcoma was diagnosed in 38 dogs. Thirty-six tumors originated from the appendicular skeleton and two from the axial skeleton. Nineteen of the dogs were treated with amputation alone, and 19 were treated with amputation and adjuvant chemotherapy consisting of doxorubicin and cisplatin. The 36 dogs with appendicular osteosarcoma had complete amputation of the affected limb, whereas the two dogs with osteosarcoma of the axial skeleton had an en bloc resection. The mean survival of the 19 dogs treated with amputation alone was 218 days (median, 175 days). Ten dogs were alive at 6 months and four survived 1 year. None of the dogs survived longer than 16 months. Radiographic lesions consistent with metastatic osteosarcoma were seen after surgery in the nine dogs in which radiographs were taken. The mean survival of the 19 dogs treated with amputation and chemotherapy was 415 days (median, 300 days). Drug toxicity was not observed. Fifteen dogs were alive at 6 months, seven dogs were alive at 1 year, 5 dogs were alive at 2 years, and two dogs were alive at 3 years or longer. One dog is alive and well at 25 months. Radiographic lesions suggestive of metastatic osteosarcoma developed in the other 18 dogs. The 19 dogs treated with amputation and chemotherapy had significantly longer survival times than the dogs treated with amputation alone.  相似文献   

3.
OBJECTIVE: To determine the incidence of regional lymph node metastasis in dogs with appendicular osteosarcoma and determine whether regional lymph node metastasis was associated with shortened disease-free interval or survival time. DESIGN: Retrospective study. ANIMALS: 228 dogs with appendicular osteosarcoma in which regional lymph nodes were examined histologically at the time of limb amputation. PROCEDURE: Information collected from the medical records included signalment; affected site; initial serum alkaline phosphatase activity; whether treatment involved adjuvant chemotherapy and, if so, chemotherapeutic agents administered and number of treatments; disease-free interval; and survival time. RESULTS: 10 (4.4%) dogs had histologic evidence of regional lymph node metastasis at the time of amputation. Median disease-free interval for dogs without regional lymph node metastasis (238 days; range, 0 to 1,067 days) was significantly longer than median disease-free interval for dogs with regional lymph node metastasis (48 days; range, 2 to 269 days). Median survival time for dogs without lymph node metastasis (318 days; range, 20 to 1,711 days) was significantly longer than median survival time for dogs with lymph node metastasis (59 days; range, 19 to 365 days). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that regional lymph node metastasis is rare in dogs with appendicular osteosarcoma but that dogs with lymph node metastasis have a poorer prognosis than do dogs without.  相似文献   

4.
5.
Twelve dogs were diagnosed with osteosarcoma of the proximal radius or distal humerus from 1990 to 2002, representing 1.0% of all dogs diagnosed with appendicular osteosarcoma. The median body weight (29.8 kg) was significantly less than that of dogs with appendicular osteosarcoma at other sites. Ten dogs were treated with amputation and chemotherapy. These dogs had a metastatic rate of 60%, a median metastasis-free interval of 356 days, and a median survival time of 824 days. There were no significant differences in metastasis-free interval or survival time between dogs with osteosarcoma of the proximal radius or distal humerus and dogs with appendicular osteosarcoma at other sites.  相似文献   

6.
Amputation and Cisplatin for Treatment of Canine Osteosarcoma   总被引:2,自引:0,他引:2  
Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two postoperative [corrected] doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1, 282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma.  相似文献   

7.
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   

8.
Sixteen dogs with histologically confirmed appendicular osteosarcoma were treated by amputation followed by cisplatin and doxorubicin chemotherapy. All dogs began chemotherapy within 24 hours of surgery. Cisplatin was administered at 50 mg/m2 intravenously (IV) concurrent with saline-induced diuresis. Doxorubicin was administered 24 hours later at 15 mg/m2 as a slow IV bolus. This protocol was given on a 21-day cycle for 4 cycles. No dose delays were required, but dose reduction of doxorubicin was required in 2 dogs because of neutropenia. Thoracic radiography was performed every 2 months after completion of therapy to monitor for metastatic disease. Two dogs were still alive and free from disease at the time of last contact (24 and 75 months, respectively). Postmortem examinations were performed on 13 of the 14 dogs that died. Eight of these dogs were euthanized because of metastatic osteosarcoma. Of the remaining 5 dogs, euthanasia was performed because of complications of idiopathic megaesophagus (n = 1), arthritis (n = 2), and hemangiosarcoma (n = 2). The median disease-free interval and survival times were 15.7 and 18 months, respectively. When compared to a historical group of 36 dogs with appendicular osteosarcoma treated with surgery and 4 doses of cisplatin. both disease-free interval and overall survival were significantly longer in the study population (P < .015 and P < .007, respectively).  相似文献   

9.
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   

10.
The results achieved in 18 dogs following the use of frozen bone cortical allografts for limb-sparing resection of non-metastatic canine appendicular osteosarcoma are presented. Three to five cisplatin doses (70 mg/m2) were administered, starting the day after surgery. The mean and median survival times were 478 and 266 days (range 80 to 2,611 days), respectively. The survival rate was 94 per cent at three months, 78 per cent at six months, 35 per cent at 12 months, 23 per cent at 18 months and 19 per cent at 24 months; the disease-free interval was 80 to 1,246 days (mean 365 days, median 266 days). Lung metastasis developed in 55 per cent of the dogs within one year. Complications were observed in 14/18 dogs (78 per cent), comprising local recurrence (28 per cent), allograft infection (39 per cent) and implant failure (11 per cent). Despite complications, limb sparing is a useful alternative to amputation in selected cases of appendicular osteosarcoma.  相似文献   

11.
Background: Appendicular osteosarcoma (OSA), the most common bone tumor in dogs, is typically treated by amputation and adjuvant chemotherapy. Despite numerous efforts, the median survival time (MST) for dogs receiving a platinum compound, doxorubicin, or a combination of these remains at 8–12 months. Evidence from studies in mice suggests that gemcitabine has activity against OSA in vivo. Our preliminary work demonstrated that the addition of low‐dosage (10 mM) gemcitabine to carboplatin resulted in synergistic inhibition of OSA cell viability in vitro. Objective: The purpose of the following study was to determine whether the addition of low‐dosage (2 mg/kg) gemcitabine to carboplatin chemotherapy in dogs with OSA after amputation would improve MST over carboplatin monotherapy. Animals: Fifty dogs with histologically confirmed appendicular OSA. Methods: Dogs were treated prospectively with amputation and up to 4 dosages of carboplatin and gemcitabine in combination every 3 weeks. Results: The chemotherapeutic regimen was well tolerated with only 5 episodes of grade 3 or 4 hematologic toxicity. The median disease‐free interval (DFI) was 203 days and the MST was 279 for all dogs in this study. The 1‐ and 2‐year survival rates were 29.5 and 11.3%, respectively. Dogs with proximal humeral OSA had a shorter median DFI (P= .04) compared with dogs with OSA in other locations. Conclusions and Clinical Importance: These results are comparable to those reported for carboplatin monotherapy indicating that the addition of gemcitabine to carboplatin in dogs with appendicular OSA does not appear to improve outcome.  相似文献   

12.
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   

13.
Twenty-four client-owned dogs with histologically diagnosed appendicular osteosarcoma (OSA) and no evidence of gross metastatic disease were treated with amputation or limb salvage followed by combination chemotherapy consisting of carboplatin (175mg/ m2 IV, day 1) and doxorubicin (15 mg/m2 IV, day 2) given on a 21-day cycle for a maximum of 4 cycles. Hematologic and gastrointestinal adverse effects were graded according to National Cancer Institute guidelines. Thoracic radiographs were obtained before the 3rd chemotherapy cycle and then every 2 months. Median disease-free interval was 195 days (95% confidence interval 111-228 days) and median survival was 235 days (95% confidence interval 150-283 days). Two patients required dose reductions: 1 for grade 3 thrombocytopenia and 1 for grade 3 adverse gastrointestinal effects. Patients with a longer duration of clinical signs before definitive diagnosis and surgery (greater than 30 days) were more likely to develop progressive disease and to die or be euthanized because of progressive disease on any day; hazard ratios were 3.0 (P = .02) and 3.7 (P .02), respectively. In conclusion, although this combination chemotherapy protocol was well tolerated, it did not provide any improvement over historical single-agent protocols.  相似文献   

14.
Use of cisplatin for treatment of appendicular osteosarcoma in dogs   总被引:4,自引:0,他引:4  
Nineteen dogs were treated for osteosarcoma of the appendicular skeleton. Eleven dogs treated by amputation and adjunctive cisplatin chemotherapy had a significantly longer (P less than 0.003) median survival time of 43 weeks (range, 20 to 108 weeks) than did 8 dogs whose median survival time was 14.5 weeks (range, 8 to 46 weeks) after amputation alone. All 11 dogs given cisplatin were evaluated for signs of drug toxicosis. Transient episodes of vomiting were recorded in 9 of 11 dogs. Additional toxic effects included gradual decreases in endogenous creatinine clearance in 3 dogs and thrombocytopenia in 1 dog. On the basis of prolonged survival times and minimal adverse effects, we concluded that cisplatin has promise as an effective and relatively nontoxic agent, when combined with amputation, for treatment of dogs with osteosarcoma of the appendicular skeleton.  相似文献   

15.
Stereotactic radiosurgery (SRS) involves precise delivery of a single large dose of radiation to a designated tumor target. This report describes use of SRS in combination with a frameless stereotactic localization system to treat 11 dogs with appendicular osteosarcomas. Five dogs were treated with SRS alone; 6 were treated with a combination of SRS and chemotherapy. Overall median survival time was 363 days (range, 145 to 763 days), with 6 dogs still alive 90, 142, 234, 367, 633, and 763 days after SRS. Limb function was good or excellent in all 6 dogs that were still alive. Results in these dogs suggest that SRS may be a viable option for dogs with appendicular osteosarcoma, with the potential to provide long-term local tumor control and improvement in limb function, especially when combined with chemotherapy. Because of the destructive nature of osteosarcoma and limitations of SRS, dogs with tumors that are small and have caused minimal bone destruction would likely be the best candidates for this procedure.  相似文献   

16.
Toxicosis associated with doxorubicin and cisplatin administration starting either 2 or 10 days after limb amputation for osteosarcoma was examined retrospectively in dogs. The purpose was to determine whether dosage and timing of chemotherapy affected rates of toxicosis after administration of the 1st treatment. Records of 100 dogs with appendicular osteosarcoma without evidence of metastases or concurrent disease were examined. Dogs received chemotherapy with doxorubicin and cisplatin every 3 weeks for 3 treatments starting 2 days (n = 51) or 10 days (n = 49) after amputation. The dosage of cisplatin was 60 mg/m2 and was given with 6-hour saline diuresis and butorphanol. Doxorubicin was given at 12.5-25 mg/ml during fluid administration. Hematologic data were collected before and weekly after treatment. Client interviews were conducted to assess gastrointestinal toxicosis during the interval between treatments. The reported toxicoses were graded on a scale of 0 to 4. Dogs receiving 25 mg/m2 of doxorubicin experienced greater rates of grade 4 toxicity (67%; n = 6) than dogs in groups receiving 12.5-20 mg/m2 of doxorubicin (< or = 25%; n = 94, P = .03). Dogs in the Day 2 group experienced greater rates (35%) of grade 4 toxicity than dogs in the Day 10 group (12%, P = .007). We concluded that chemotherapy administered 2 days after surgery produced an unacceptable level of toxicoses. except at greatly reduced dosages, and that even with a delay of treatment, 25 mg/m2 of doxorubicin, when given in combination with cisplatin at 60 mg/m2, was too toxic for routine use.  相似文献   

17.
18.
Thirty-five dogs with appendicular osteosarcoma underwent amputation and chemotherapy with cisplatin and doxorubicin every 21 days for up to four cycles. Sixteen dogs completed all four cycles. Two dogs had therapy discontinued because of metastases. The remaining 17 dogs experienced toxicities necessitating protocol alteration or discontinuation. The median survival time of 300 days was not improved over previously reported single-agent protocols, but the 10 dogs that survived to a year lived a median of 510 days.  相似文献   

19.
OBJECTIVE: To evaluate survival times and palliative effects associated with the use of samarium Sm 153 lexidronam in dogs with primary bone tumors. DESIGN: Retrospective case series. ANIMALS: 35 dogs with primary appendicular (n = 32) or axial (3) bone tumors. PROCEDURES: 1 to 4 doses of samarium Sm 153 lexidronam were administered at a rate of 37 MBq/kg (16.8 MBq/lb), IV. Response to treatment, measured by lameness improvement, and survival time were determined. RESULTS: Of the 32 dogs with appendicular tumors, 20 (63%) had an improvement in the severity of lameness 2 weeks after administration of the first dose of radioactive samarium, 8 (25%) had no change in the severity of lameness, and 4 (12%) had a worsening. Overall median survival time was 100 days, with 3 dogs (8.6%) alive after 1 year. Median survival time for the 32 dogs with appendicular tumors was 93 days, with 3 (9.4%) alive after 1 year. This was not significantly different from the median survival time of 134 days for a historical cohort of 162 dogs with appendicular osteosarcoma that underwent amputation as the only treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that samarium Sm 153 lexidronam may be useful in the palliation of pain in dogs with primary bone tumors that are not candidates for curative-intent treatment.  相似文献   

20.
Partial mandibulectomy was performed for the treatment of benign or malignant oral tumors in 142 dogs. Forty-two dogs with a benign tumor (ameloblastoma) had a 22.5 month (range, 6 to 74 months) median disease-free interval, with a 97% 1-year survival rate; there was local recurrence in one dog. Twenty-four dogs with squamous cell carcinoma had a disease-free interval of 26 months (range, 6 to 84 months), with a 91% 1-year survival rate; recurrence and metastasis developed in two dogs and metastatic disease in one dog. Based on survival curves, 37 dogs with a melanoma had a median survival time of 9.9 months (range, 1 to 36 months), with a 21% 1-year survival rate; 20 dogs died or were euthanatized for recurrent or metastatic disease. Twenty dogs with osteosarcoma had a median survival time of 13.6 months (range, 3 to 28 months), with a 35% 1-year survival rate; nine dogs died or were euthanatized for recurrent or metastatic disease. Nineteen dogs with fibrosarcoma had median survival time of 10.6 months (range, 3 to 32 months), with a 50% 1-year survival rate; 12 dogs died or were euthanatized for recurrent or metastatic disease. Results of this and previous studies demonstrated that partial mandibulectomy was effective in prolonging survival and decreasing recurrence for squamous cell carcinoma and ameloblastoma. Progressive disease and corresponding low survival times were common in dogs with melanoma, osteosarcoma, and fibrosarcoma. There were no differences in survival times or the progression of disease among five partial hemimandibulectomy procedures. The high rates of recurrence and metastasis in dogs with these tumors suggest a need for evaluation of ancillary chemotherapy and local radiation therapy to decrease the prevalence of progressive disease.  相似文献   

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