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唑来膦酸是第三代双膦酸盐药物,主要用于治疗恶性高钙血症及骨转移癌。目前的研究发现,除抑制骨吸收外唑来膦酸还具有直接和间接的抗肿瘤活性。其中抑制肿瘤血管形成是其间接抗肿瘤作用机制之一。其抗肿瘤血管生成作用可能机制如下:(1)抑制肿瘤细胞及肿瘤间质细胞分泌VEGF,调节VEGF-VEGFR自分泌环抑制血管生成;(2)抑制血管内皮细胞迁移、黏附作用;(3)诱导循环内皮细胞祖细胞凋亡,抑制肿瘤细胞及肿瘤浸润巨噬细胞分泌MMPs;(4)抑制肿瘤细胞血管生成拟态。但唑来膦酸抗肿瘤活性的用药剂量不同于目前治疗骨转移的剂量,其抗肿瘤血管生成拟态的作用机制尚未明确,需要进一步研究。 相似文献
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目的:探讨乳腺癌骨转移患者的临床、病理、治疗及预后因素。方法:收集2005年1 月至2013年4 月天津医科大学肿瘤医院收治的183 例至少接受6 个月双膦酸盐治疗的乳腺癌骨转移患者的临床资料,根据双膦酸盐类型分为帕米膦酸二钠组、唑来膦酸组及帕米膦酸二钠序贯唑来膦酸组,探讨骨转移的特点、骨相关事件(skeletal-related events,SREs)、治疗及预后特征。结果:胸椎和肋骨为骨转移的常见转移部位,骨转移至发生首次SREs的中位时间为4.2 个月,51.9%(95/ 183)患者发生SREs,累计SREs事件数达167 次,其中110 次(65.9%)发生在骨转移后1 年内,SREs类型以骨放疗为主。患者在不同双膦酸盐药物组的SREs发生率差异无统计学意义(P > 0.05)。 183 例患者骨转移后的中位生存期为43.1 个月,激素受体状态、无病生存期、是否合并内脏转移及脊柱转移与否是乳腺癌骨转移患者的独立预后因素(P < 0.05)。 结论:胸椎和肋骨是乳腺癌骨转移的常见转移部位,SREs主要发生在骨转移后1 年内并以骨放疗为主。激素受体阴性、无病生存期短、合并内脏及脊柱转移是影响乳腺癌患者骨转移不良预后的独立因素。 相似文献
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唑来膦酸治疗恶性肿瘤骨转移60例的疗效观察 总被引:1,自引:0,他引:1
双膦酸盐类是目前治疗骨转移公认的有效药物.这类化合物通过抑制骨吸收来减少骨并发症的发生.唑来膦酸是一种高效、含氮基的第三代双膦酸盐类药物,能明显缓解骨转移患者疼痛,改善患者的生活质量,防止或减少骨骼相关事件发生,不良反应少. 相似文献
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[目的]观察唑来膦酸治疗非小细胞肺癌骨转移的疗效及安全性。[方法]临床确诊的41例非小细胞肺癌骨转移患者,唑来膦酸4mg,溶于100ml生理盐水,静脉滴注15min,每3~5周重复。[结果]用药第7d骨转移疼痛缓解有效率为78.0%。骨不良事件发生率中,骨放疗为12.2%,椎体压缩、变形为7.3%,脊髓压迫为4.9%,无1例病理性骨折、骨手术及高钙血症的发生。不良反应有流感样症状、发热、肾功能降低及眼结膜炎。[结论]唑来膦酸可以有效控制非小细胞肺癌骨转移性癌痛,预防、减少和延缓骨不良事件的发生,临床应用安全性好,无严重不良反应。 相似文献
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目的探讨化疗联合唑来膦酸治疗肺癌骨转移的临床效果。方法将收治的64例肺癌骨转移患者,随机分为对照组和观察组,对照组患者采用诺维本联合顺铂(NP)方案治疗,观察组患者在对照组的基础上加用唑来膦酸治疗。比较两组患者的疼痛缓解情况,活动能力改善情况,骨病灶改善情况,生存质量改善情况及不良反应发生情况。结果观察组患者疼痛总缓解率、活动能力恢复总有效率、骨病灶疗效总有效率和生存质量改善率(84.4%、84.4%、68.8%和81.3%)显著高于对照组(53.1%、56.3%、50.0%和46.9%),差异有统计学意义(P〈0.05)。两组患者不良反应发生情况差异无统计学意义(P〉0.05)。结论化疗联合唑来膦酸用于治疗肺癌骨转移,可显著减轻骨痛等相关事件,显著改善患者的生活质量及活动能力,不良反应少,使用方便,值得临床推广应用。 相似文献
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目的 比较唑来膦酸联合化疗及伊班膦酸联合化疗预防和治疗多发性骨髓瘤(MM)骨并发症的效果及其安全性。方法 选择2005年3月至2008年3月中山大学附属第一医院治疗的MM患者77例,按照用药情况分为唑来膦酸联合化疗组24例,伊班膦酸联合化疗组26例,单纯化疗组27例。结果 唑来膦酸联合化疗组、伊班膦酸联合化疗组和单纯化疗组患者发生1次骨相关事件(SRE)的比例分别为25.0 %、26.9 %、48.1 %(P=0.145)。唑来膦酸联合化疗组、伊班膦酸联合化疗组发生脊柱压缩性骨折(VCF)的比例分别为4.2 %和7.7 %,少于单纯化疗组的14.8 %(P=0.115)。三组的中位首次发生SRE时间(T-SRE)分别为7.5、6.5和4.5个月(P<0.001)。唑来膦酸联合化疗组止痛有效率为66.7 %,伊班膦酸联合化疗组有效率为69.2 %,单纯化疗组为29.6 %,差异有统计学意义(P=0.028)。唑来膦酸联合化疗组治疗后的血钙水平低于伊班膦酸联合化疗组(P=0.016),降至正常水平所需时间也较伊班膦酸联合化疗组短(P=0.04)。唑来膦酸联合化疗组和伊班膦酸联合化疗组的不良反应发生率低,两组不良反应发生率差异无统计学意义(P>0.05)。结论 应用双膦酸盐可减少MM患者SRE的发生率和VCF。唑来膦酸在减少VCF发生率、减轻骨痛上与伊班膦酸类似,优于单纯化疗组;唑来膦酸在降低血钙水平方面优于伊班膦酸。唑来膦酸临床应用不良反应少,患者均可耐受。 相似文献
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K Nakamura Y Yamada CJ Rosser M Arakawa K Zennmai Y Kato M Watanabe R Katsuda M Tobiume K Naruse S Aoki T Taki H Saito T Hasegawa N Honda 《Oncology letters》2010,1(1):13-16
Zoledronic acid (ZOL) is a new generation bisphosphonate with improved efficacy benefits over pamidronate in preclinical testing. In addition, ZOL is superior to pamidronate in the treatment of hypercalcemia of malignancy. ZOL is also the first bisphosphonate to demonstrate efficacy in patients with bone metastases from solid tumors other than breast cancer, such as prostate cancer. In this study, we investigated ZOL treatment in 17 Japanese men with advanced prostate cancer, treated at the Aichi Medical University Hospital between August 2006 and November 2007. The 17 patients had biopsy-confirmed prostate cancer and were found to harbor bone metastasis upon bone scintigraphy. ZOL was administered intravenously at a dose of 4 mg over 15 min every 4 weeks. ZOL was well tolerated with mild renal dysfunction in 2 patients (11.8%), while 1 patient (5.8%) developed skin rash. No significant side effects were observed. Subjective improvement in bone pain was reported in 14 patients (32.4%). ZOL, therefore, is a safe and effective drug that remains an important component of the urologist's armamentarium against advanced prostate cancer. 相似文献
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Bone is the most common site for metastasis from solid tumors, and the majority of patients will develop bone metastases during the natural course of their disease. Bisphosphonates are an effective treatment for preventing skeletal-related events in patients with bone metastases and may preserve functional independence and quality of life. Although several bisphosphonates have been investigated in patients with solid tumors, only zoledronic acid (ZOL) is approved by the US Food and Drug Administration and the European Medicines Agency for preventing skeletal-related events in patients across a broad range of solid tumors. In addition, bisphosphonates, notably ZOL, prevent cancer treatment-induced bone loss in breast and prostate cancer patients who are receiving endocrine therapy. It also has been demonstrated that ZOL directly and indirectly inhibits cancer cell growth in vitro and growth and tumorigenesis in animal model systems. These properties may produce clinically meaningful benefits. In recent clinical studies in patients with cancer, ZOL improved overall and prolonged disease-free survival. Ongoing clinical trials in patients with solid tumors will provide further insight into the potential of ZOL to prevent distant metastases and improve survival. 相似文献
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Agatha Labrinidis Shelley Hay Vasilios Liapis David M. Findlay Andreas Evdokiou 《International journal of cancer. Journal international du cancer》2010,127(2):345-354
Osteosarcoma (OS) is the most common primary malignant tumor of bone in children and adolescents. In spite of successful control of the primary tumor, death from lung metastasis occurs in more than a third of patients. To investigate the efficacy of zoledronic acid (ZOL) on the development, progression and metastatic spread of OS, we used a rat model of OS, with features of the disease similar to human patients, including spontaneous metastasis to lungs. Rat OS cells were inoculated into the tibial marrow cavity of syngeneic rats. OS development was associated with osteolysis mixed with new bone formation, adjacent to the periosteum and extended into the surrounding soft tissue. Metastatic foci in the lungs formed 3–4 weeks postcancer cell transplantation. Treatment with a clinically relevant dose of ZOL was initiated 1 week after tumors were established and continued once weekly or as a single dose. ZOL preserved the integrity of both trabecular and cortical bone and reduced tumor‐induced bone formation. However, the overall tumor burden at the primary site was not reduced because of the persistent growth of cancer cells in the extramedullary space, which was not affected by ZOL treatment. ZOL treatment failed to prevent the metastatic spread of OS to the lungs. These findings suggest that ZOL as a single agent protects against OS‐induced bone destruction but lacks efficacy against pulmonary metastases in this rat model. ZOL may have potential value as an adjuvant therapy in patients with established OS. 相似文献
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Makoto Toneri Shinji Miwa Yong Zhang Cameron Hu Shuya Yano Yasunori Matsumoto Michael Bouvet Hayao Nakanishi Robert M. Hoffman Ming Zhao 《Oncotarget》2015,6(31):31335-31343
Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting. 相似文献
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Lu S Zhang J Zhou Z Liao ML He WZ Zhou XY Li ZM Xiang JQ Wang JJ Chen HQ 《Oncology reports》2008,20(3):581-587
Zoledronic acid (Zometa, ZOL) and cytotoxic chemotherapy agents have been reported to have synergistic antitumor activities. However, there is limited data on the effects of combination therapies on the development of bone metastasis in animal models of lung cancer. The purpose of this study was to establish a human lung adenocarcinoma cell line with high bone metastatic potential in an immunodeficient mouse model and to evaluate the synergistic inhibitory activity of zoledronate and paclitaxel (P) on bone metastasis in nude mice. A human lung adenocarcinoma cell line with high bone metastatic potential (SPC-A1-BM) was established by 10 rounds of in vivo selection. Cells were inoculated into the cardiac ventricle of NIH-BNX mice, which were treated 8 days later with: ZOL (0.2 mg/kg s.c. twice weekly) alone, P (6.0 mg/kg every week, i.p.) alone, P + ZOL, or vehicle (10 mice per group). Tumor growth was evaluated with bone scans, X-rays and in situ immunohistochemistry. Serum n-telopeptide of type I collagen (NTX) was measured by ELISA. Survival was assessed using the Kaplan-Meier method. Bone scan, radiographic and histological assessments revealed fewer bone metastases in all treatment groups vs. vehicle, with P + ZOL significantly reducing the incidence of bone metastases detected by bone scans (P=0.020) and X-rays (P=0.036). A histological analysis revealed marginal differences in the number of bone metastases between P + ZOL and vehicle (P=0.058). There was a trend towards differences in survival between the groups (P=0.1511) and survival was significantly longer for the P + ZOL group vs. vehicle (P=0.022). Compared with vehicle and ZOL alone, cancerous cells in the bone of mice treated with P + ZOL expressed higher levels of Bax and lower levels of Bcl-2 and Bcl-xl. ZOL produced a trend towards reduced NTX levels vs. vehicle and P + ZOL produced a profound reduction in NTX vs. vehicle (P=0.022). The results of this study indicated that zoledronate enhanced the efficacy of paclitaxel synergistically, by reducing the incidence of bone metastasis from lung cancer and prolonging survival in a mouse model of non-small cell lung cancer with a high potential for metastasis to bone. 相似文献
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Zoledronic acid inhibits visceral metastases in the 4T1/luc mouse breast cancer model. 总被引:6,自引:0,他引:6
Toru Hiraga Paul J Williams Akimi Ueda Daisuke Tamura Toshiyuki Yoneda 《Clinical cancer research》2004,10(13):4559-4567
PURPOSE: It is established that bisphosphonates (BPs), specific inhibitors of osteoclasts, have beneficial effects on bone metastases of breast cancer. In addition, recent studies have reported that BPs have anticancer effects and suppress visceral metastases, too. However, the results of clinical studies are still conflicting. In the present study, we examined the effects of the BP zoledronic acid (ZOL), one of the most potent BPs currently available, on visceral metastases of breast cancer using an animal model in which mouse breast cancer cells 4T1/luc implanted at the orthotopic mammary fat pad spontaneously metastasize to multiple organs including bone, lung, and liver in female BALB/c mice. Experimental Design and RESULTS: The 4T1/luc-bearing mice received single or four i.v. injections of ZOL (0.5 or 5 microg/mouse) during the whole experimental period. Bone metastases were reduced by the ZOL treatment. More importantly, ZOL significantly suppressed lung and liver metastases. Furthermore, ZOL prolonged overall survival of the tumor-bearing mice. Of interest, apoptosis in 4T1/luc cells colonized in bone was increased by ZOL; however, those in lung were not changed. In vitro studies demonstrated that ZOL inhibited cell migration and invasion and promoted apoptosis of 4T1/luc cells. CONCLUSIONS: These results are consistent with the notion that ZOL affects breast cancer metastasis to visceral organs as well as bone. These effects of ZOL may be attributable to inhibition of migration and invasion of breast cancer cells. Clinical relevance of our experimental results needs to be determined in breast cancer patients with visceral metastases. 相似文献
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Francini F Pascucci A Bargagli G Francini E Conca R Miano ST Martellucci I Migali C Gotti G Fiaschi AI Cozzolino A Petrioli R 《International journal of clinical oncology / Japan Society of Clinical Oncology》2011,16(3):264-269
Background
The aim of this study was to assess the early effects of zoledronic acid (ZOL) and oral ibandronate (IBA) on the bone resorption marker s-CTX (serum C-telopeptide of collagen type I) and the bone formation marker B-ALP (bone-alkaline phosphatase) in patients with bone metastases from non-small cell lung cancer (NSCLC).Methods
Fifty-five patients with at least one site of bone metastasis secondary to NSCLC were randomly assigned to receive intravenous ZOL 4?mg every 4?weeks, or oral IBA 50?mg/day.Results
At 1?month of treatment, s-CTX was reduced by 54.8% (95% CI 40.4?C59.8%) in the ZOL group (26 evaluable patients) compared with 38.2% (95% CI 29.8?C48.7%) in the oral IBA group (27 evaluable patients) (p?=?0.03). At 3?months, s-CTX was reduced by 72.6% (95% CI 58.6?C71.3%) in the ZOL group, compared with 66.4% (95% CI 54.3?C79.5%) in the oral IBA group (p?=?0.22). Both bisphosphonates similarly decreased the bone marker B-ALP at 1?month (ZOL 24.7%, 95% CI 3.6?C39.5%, and IBA 24.2%, 95% CI 2.8?C43.4%) and 3?months (ZOL 28.6%, 95% CI +2.8?C43.3%, and IBA 24.2%, 95% CI 3.2?C47.4%). Both bisphosphonates were well tolerated.Conclusion
Considering the changes in bone markers, ZOL and oral IBA show comparable efficacy in patients with NSCLC and bone metastases. 相似文献19.
Kostantinos Zarogoulidis Eufimia Boutsikou Pavlos Zarogoulidis Ellada Eleftheriadou Theodore Kontakiotis Hellie Lithoxopoulou George Tzanakakis Ioannis Kanakis Nikos K. Karamanos 《International journal of cancer. Journal international du cancer》2009,125(7):1705-1709
Bone metastases occur in 20–40% of patients with lung cancer. Recent studies demonstrate a direct antiproliferative effect of 3rd generation bisphosphonates (BPs) on lung tumors, which may influence the survival. Therefore, we examined the clinical impact of zoledronic acid (ZOL; Zometa®), a 3rd generation BP, with a focus on the survival, time to progression and pain effect in lung cancer patients with bone metastases. Lung cancer patients (n = 144, Stage IV) with evidence of metastasis bone scan were included. Eighty‐seven of 144 experienced bone pain and received ZOL, 4 mg i.v. every 21 days (Group A), whereas the other 57 patients received no ZOL (Group B). All patients were treated with a combination chemotherapy consisted of docetaxel 100 mg/m2 and carboplatin AUC = 6. It was found that Group A had a statistically significant longer survival (p < 0.01) when compared to Group B. A statistically significant positive correlation was found between the number of cycles of therapy with ZOL and total patient survival (p < 0.01, Pearson correlation) and time to progression (p < 0.01). Pain effect of ZOL had no significant difference between the 2 groups of patients (p > 0.05). Urine N‐telopeptide of type I collagen (NTx) levels decreased in patients with NTx ≤ 29 nM BCE/mM creatinine at baseline after treatment with ZOL. The results of our study suggest that the addition of ZOL increases overall survival in lung cancer patients with bone metastases. The longer period of receiving ZOL, the better effect on survival and time to progression. © 2009 UICC 相似文献