国产唑来膦酸(博来宁)与帕米膦酸二钠(博宁)治疗癌性骨痛随机双盲双模拟多中心Ⅱ期临床研究

目的：评价国产注射用唑来膦酸（博采宁）治疗癌性骨痛的临床疗效和安全性。方法：采用多中心、随机双盲对照试验将237例癌性骨痛患者随机分为试验组和对照组。试验组接受唑来膦酸4mg。静脉滴注15min。对照组接受帕米膦酸二钠（博宁）90mg．静脉滴注4h。用药4周内逐日评价骨痛的变化及不良反应。结果：可评价疗效219例，其中试验组112例，对照组107例；临床观察指标：疗后14天内最佳疗效：试验组完全缓解（CR）10．08％（12／112），部分缓解（PR）53．78％（64／112），临床获益率（CR＋PR＋MR）90．75％；对照组完全缓解5．08％（6／107），部分缓解54．24％（64／107），临床获益率83．90％，两组比较无显著性差异（P〉0．05）。次要观察指标：1）疗后14天内每天的临床疗效：试验组给药后第5、7—12天共7天试验组每日临床疗效优于对照组（P〈0．05）。2）疗后28天内最佳疗效：两组比较无显著性差异（P〉0．05）。3）疗后14天内缓解的维持时间：试验组和对照组完全缓解的维持时间分别为5．51和3.01天（P=0．0302）．有效维持时间分别为9．02和8．02天（P〉0．05）。4）首次达临床有效（CR或PR）时间：试验组6天，对照组8天（P=0．0182），不良反应主要有发热、低钙血症、疲劳等，试验组和对照组不良反应发生率分剐为20．17％和24.58％（P〉0.05）．试验组和对照组均未见有严重肝肾功能、心电图异常等发生。结论：唑来膦酸能够有效缓解癌症骨转移患者的疼痛．其有效率及不良反应发生率与帕米膦酸二钠相当，使用安全、方便。     

帕米膦酸二钠与唑来膦酸治疗肺癌骨转移性疼痛的近期疗效及成本效益分析

目的:比较帕米膦酸二钠与唑来膦酸治疗肺癌骨转移性疼痛的近期疗效、不良反应及其对于患者住院时间及住院费用的影响.方法:将40例确诊肺癌骨转移患者随机分为2组:帕米膦酸二钠组(20例)、唑来膦酸组(20例).帕米膦酸二钠注射液60mg,加入500ml生理盐水内,静脉滴注4h;唑来膦酸注射液4mg,加入100ml生理盐水内,静脉滴注20min.两组均每4周给药1次,共2次给药.比较2组患者的疼痛控制效果、血碱性膦酸酶(AKP)、血钙的变化、平均住院时间及总住院费用.结果:帕米膦酸二钠、唑来膦酸组的获益率分别为90％及85％,不良反应发生率无明显差异,均未发生下颌骨坏死.2组治疗后AKP及血钙均明显下降(P＜0.05).2组病人的住院时间(P＞0.05)及住院费用无明显差异(P＞0.05).结论:帕米膦酸二钠与唑来膦酸应用于本研究中的肺癌病人,在疗效、不良反应及成本效益方面均无明显差异.     

唑来膦酸注射液治疗恶性肿瘤骨转移疼痛的临床观察

目的：评价唑来膦酸注射液治疗肿瘤骨转移疼痛的疗效及安全性.方法：将80例因恶性肿瘤骨转移引起中度以上疼痛患者随机分为两组,研究组（45例）予唑来膦酸注射液4 mg溶于100 ml生理盐水中静脉滴注15 min.对照组（35例）予帕米膦酸二钠注射液60 mg溶于500 ml生理盐水中静脉滴注4 h.研究期为14 d.结果：两组在治疗后第14 d的疼痛评分唑来膦酸优于帕米膦酸二钠（3.63 vs.4.95,P=0.02）.疼痛完全缓解率、部分缓解率及总疗效率两组基本相似.在达到完全缓解时间上唑来膦酸比帕米膦酸二钠要短,在达到PR时间上唑来膦酸注射液与帕米膦酸二钠注射液相似.结论：唑来膦酸相对于帕米膦酸二钠给药时间短、给药剂量小、起效快,并具有良好的耐受性和安全性.     

唑来膦酸与帕米膦酸二钠治疗恶性肿瘤骨转移性疼痛比较分析

目的比较唑来膦酸与帕米膦酸二钠治疗恶性肿瘤骨转移性疼痛的近期疗效及毒副反应。方法将46例恶性肿瘤骨转移患者随机分为2组,唑来膦酸组(24例):唑来膦酸注射液4 mg,加入100 mL生理盐水内,静脉滴注不少于15 min;帕米膦酸二钠组(22例):帕米膦酸二钠注射液60 mg,加入500 mL生理盐水内,静脉滴注4 h。2组均每4周给药1次,共3次。结果唑来膦酸组、帕米膦酸二钠组治疗有效率分别为75.0%、72.7%,比较差异无统计学意义(P>0.05)。毒副反应多为轻中度,主要表现为发热、恶心、呕吐、肌痛等,2组比较差异无统计学意义(P>0.05)。结论唑来膦酸与帕米膦酸二钠治疗恶性肿瘤骨转移性疼痛的疗效及毒副反应相近,但唑来膦酸使用更为方便。     

唑来膦酸治疗癌性骨转移疼痛的有效性和安全性研究

 目的 观察国产注射用唑来膦酸单次静脉注射治疗癌症骨转移疼痛的临床疗效和安全性，并与帕米膦酸二钠进行比较 。方法 治疗组国产唑来膦酸冻干粉剂4 mg，加入生理盐水50 ml中，静脉滴注15 min。对照组帕米膦酸二钠注射液90 mg，加入生理盐水750 ml中，静脉滴注3 h。治疗后14 d内未行化、放疗等抗肿瘤治疗。用药14 d复查，评价疗效。结果 镇痛疗效：治疗组完全缓解（CR）8例，部分缓解（PR）10例，轻微缓解（MR）4例，镇痛有效（CR+PR）率72 %，获益（CBR=CR+PR+MR）率88 %。对照组CR 5例，PR 12例，MR 3例，镇痛有效率68 %，CBR率80 %。生存质量改善情况：治疗组显效9例，有效3例，有效率48 %，对照组显效7例，有效3例，有效率40 %。结论 唑来膦酸4 mg和帕米膦酸二钠90 mg的疗效相当，唑来膦酸具有较好的方便性，患者生活受到的干扰较小，依从性好，毒副反应轻，可耐受，值得临床推广使用。     

唑来膦酸注射液治疗恶性肿瘤骨转移疼痛的临床观察

目的:评价唑来膦酸注射液治疗肿瘤骨转移疼痛的疗效及安全性.方法:将80例因恶性肿瘤骨转移引起中度以上疼痛患者随机分为两组,研究组(45例)予唑来膦酸注射液4 mg溶于100 ml生理盐水中静脉滴注15 min.对照组(35例)予帕米膦酸二钠注射液60 mg溶于500 ml生理盐水中静脉滴注4 h.研究期为14 d.结果:两组在治疗后第14 d的疼痛评分唑来膦酸优于帕米膦酸二钠(3.63 vs.4.95,P=0.02).疼痛完全缓解率、部分缓解率及总疗效率两组基本相似.在达到完全缓解时间上唑来膦酸比帕米膦酸二钠要短,在达到PR时间上唑来膦酸注射液与帕米膦酸二钠注射液相似.结论:唑来膦酸相对于帕米膦酸二钠给药时间短、给药剂量小、起效快,并具有良好的耐受性和安全性.     

唑来膦酸治疗恶性肿瘤骨转移44例临床观察

目的观察唑来膦酸注射液治疗转移性骨肿瘤的疗效及安全性。方法44例恶性肿瘤骨转移患者采用唑来膦酸(天晴依泰)注射液4mg加入0.9%氯化钠注射液100ml静脉滴注15分钟以上;同时以35例恶性肿瘤骨转移患者使用帕米膦酸二钠(博宁)注射液60mg加入0.9%氯化钠注射液500ml静脉滴注4小时以上作为对照。两组均一次性给药后观察14天。结果治疗骨痛有效率唑来膦酸组为81.08%,帕米膦酸二钠组为69.70%,两组疗效差异有显著性(P<0.05)。活动能力有效率唑来膦酸组为40.91%,帕米膦酸二钠组为45.71%,两组疗效差异无显著性(P>0.05)。不良反应发生率唑来膦酸组为45.45%,帕米膦酸二钠组为42.86%,差异无显著性(P>0.05),均主要表现为发热、低钙血症、肌肉酸痛,予对症处理后症状消失。结论唑来膦酸是一种有效的第三代双膦酸盐制剂,可方便安全地用于恶性肿瘤骨转移的治疗。     

唑来膦酸与帕米膦酸二钠治疗肺癌骨转移疼痛的对比研究

为了评价唑来膦酸注射液治疗肺癌骨转移所致骨痛的疗效及安全性,将临床确诊的肺癌骨转移患者50例随机分为唑来膦酸组25例和帕米膦酸二钠组25例.结果:唑来膦酸组和帕米膦酸二钠组治疗骨痛总有效率为76%(19/25)和72%(18/25),差异无统计学意义,P=0.798.止痛起效时间:唑来膦酸组1～11d(中位时间5d),帕米膦酸二钠组2～13d(中位时间5d),差异无统计学意义,P=0.702.止痛疗效维持时间:唑来膦酸组2～32d(中位时间24d),帕米膦酸二钠组1～29d(中位时间23d),差异无统计学意义,P=0.509.初步研究结果提示,唑来膦酸注射液治疗肺癌骨转移疼痛疗效确切,与帕米膦酸二钠相比疗效和不良反应相似.     

唑来膦酸治疗骨转移疼痛的临床研究

[目的]观察唑来膦酸治疗恶性肿瘤骨转移疼痛的临床疗效.[方法]21例恶性肿瘤骨转移患者,分为实验组(11例)和对照组(10例),分别给予唑来膦酸和帕米膦酸二钠进行治疗.[结果]实验组和对照组有效率分别是54.55%和30.00%.临床获益率分别是63.64%和30.00%,两者差异无显著性(P＞0.05).唑来膦酸组在疗效维持时间上明显长于帕米膦酸二钠组(P＜0.05).[结论]唑来膦酸可缓解肿瘤骨转移的疼痛,疗效维持时间长,副作用小,耐受性好.     

帕米膦酸二钠治疗28例恶性骨痛的临床观察

目的：对帕米膦酸二钠治疗28例恶性肿瘤骨痛进行临床观察。方法：28例恶性骨转移癌及多发性骨髓瘤患者,疼痛Ⅰ～Ⅲ,静滴帕米膦酸二钠60mg,2周后重复,共用2～4次。结果：止痛有效率60．7％（17／28）,活动能力改善有效率53．6％（15／28）。结论帕米膦酸二钠治疗恶性肿瘤溶骨性转移性疼痛疗效确实,不良反应轻微。     

Treatment of tumor-induced hypercalcemia: a solved problem?

Less than 25 years ago, tumor-induced hypercalcemia was often a lethal complication of cancer. Nowadays, it can be successfully and easily treated in at least 90% of the cases by rehydration and potent antiosteoclastic bisphosphonates. The standard therapy consists of the administration of 90 mg of pamidronate (Aredia Dry Powder) or more recently, 4 mg of zoledronic acid (Zometa)], which is even more efficient, at least in patients without bone metastases. Recurrent hypercalcemia is nevertheless difficult to control and antibodies against parathyroid-hormone-related protein may prove to be a useful treatment.     

Optimising treatment of bone metastases by Aredia™ and Zometa™

Metastatic bone disease develops as a result of the many interactions between tumour cells and bone cells. This leads to disruption of normal bone metabolism, with the increased osteoclast activity seen in most, if not all, tumor types providing a rational target for treatment. The clinical course of metastatic bone disease in multiple myeloma, breast and prostate cancers is relatively long, with patients experiencing sequential skeletal complications over a period of several years. These include bone pain, fractures, hypercalcaemia, and spinal cord compression, all of which may profoundly impair a patient's quality of life. External beam radiotherapy and systemic endocrine and cytotoxic treatments are the mainstay of treatment in advanced cancers. However, it is now clear that the bisphosphonates provide an additional treatment strategy, which reduces both the symptoms and complications of bone involvement. Pamidronate (Aredia(TM)) is the most widely evaluated bisphosphonate and is recommended for most patients with multiple myeloma or breast cancer with bone metastases. Current research aims include the evaluation of new potent bisphosphonates such as zoledronic acid (Zometa(TM)). It is hoped that this compound is not only more convenient and easier to administer but also more effective in inhibiting skeletal morbidity. Zometa may also have some direct anticancer activity. Preclinical studies with Zometa have demonstrated its potential in malignant bone disease. Clinical studies in treatment of hypercalcemia of malignancy have been completed, as have Phase I and II trials in patients with cancer and pre-existing bone metastases. Three randomized, double-blind, controlled Phase III trials are now ongoing to establish the efficacy and safety of Zometa in treatment of bone metastases in patients with osteolytic and osteoblastic lesions. Additionally, new specific molecules such as osteoprotogerin have been developed that are based on our improved understanding of the cellular signalling mechanisms involved in cancer induced bone disease. These potent molecules are now entering clinical trials. Ongoing research is aimed at trying to define the optimum route, dose, schedule and type of bisphosphonate in metastatic bone disease and their use in the prevention and treatment of osteoporosis in cancer patients. In vitro suggestions of direct anti-cancer activity and some promising clinical data in early breast cancer have resulted in considerable interest in the possible adjuvant use of bisphosphonates to inhibit the development of bone metastases.     

Safety of intravenous and oral bisphosphonates and compliance with dosing regimens

Patients with advanced cancers--particularly breast and prostate cancers--are at high risk for bone metastasis, leading to accelerated bone resorption and clinically significant skeletal morbidity. Bisphosphonates are effective inhibitors of bone resorption and reduce the risk of skeletal complications in patients with bone metastases. The standard routes of administration for bisphosphonates used in clinical practice are either oral or i.v. infusion. Oral administration of bisphosphonates is complicated by poor bioavailability (generally <5%) and poor gastrointestinal tolerability. First-generation bisphosphonates, such as clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), must be administered at high oral doses (1,600-3,200 mg/day) to achieve therapeutic effects, which leads to poor tolerability and compliance with oral dosing regimens. Infusion of bisphosphonates is associated with dose- and infusion-rate-dependent effects on renal function. In particular, high bisphosphonate doses (e.g., 1,500 mg clodronate) can cause severe renal toxicity unless infused slowly over many hours. In contrast, the newer, more potent bisphosphonates effectively inhibit bone resorption at micromolar concentrations, and the small doses required can be administered via relatively short i.v. infusions without adversely affecting renal function. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ) is a new generation bisphosphonate, and the recommended dose of 4 mg can be safely infused over 15 minutes. The 90-mg dose of pamidronate (Aredia; Novartis Pharmaceuticals Corp.) and the 6-mg dose of ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) require 1- to 4-hour infusions. Intravenous bisphosphonates require less frequent dosing (once a month) and are generally well tolerated with long-term use in patients with bone metastases. Zoledronic acid has demonstrated the broadest clinical activity in patients with bone metastases.     

Aromatase inhibitors and bone loss

The aromatase inhibitors (AIs) anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are significantly more effective than the selective estrogen-receptor modulator (SERM) tamoxifen in preventing recurrence in estrogen receptor-positive early breast cancer. Aromatase inhibitors are likely to replace SERMs as first-line adjuvant therapy for many patients. However, AIs are associated with significantly more osteoporotic fractures and greater bone mineral loss. As antiresorptive agents, oral and intravenous bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), pamidronate (Aredia), and zoledronic acid (Zometa) have efficacy in preventing postmenopausal osteoporosis, cancer treatment-related bone loss, or skeletal complications of metastatic disease. Clinical practice guidelines recommend baseline and annual follow-up bone density monitoring for all patients initiating AI therapy. Bisphosphonate therapy should be prescribed for patients with osteoporosis (T score < -2.5) and considered on an individual basis for those with osteopenia (T score < -1). Modifiable lifestyle behaviors including adequate calcium and vitamin D intake, weight-bearing exercise, and smoking cessation should be addressed. Adverse events associated with bisphosphonates include gastrointestinal toxicity, renal toxicity, and osteonecrosis of the jaw. These safety concerns should be balanced with the potential of bisphosphonates to minimize or prevent the debilitating effects of AI-associated bone loss in patients with early, hormone receptor-positive breast cancer.     

Management of Metastatic Bone Disease and Hypercalcemia of Malignancy

Thirty years of research have established bisphosphonates as the most effective agents for the inhibition of osteoclast-mediated bone resorption, and they play an important role in the management of malignant bone disease. Bisphosphonates have been systematically improved through chemical engineering, and the newest nitrogen-containing compounds, including zoledronic acid and ibandronate, are 1000-fold more potent than first-generation compounds. Consequently, they can be administered at low molar doses via short intravenous infusions without compromising renal safety. Bisphosphonates have a variety of metabolic effects on osteoclasts. Nitrogen-containing bisphosphonates inhibit protein prenylation via the mevalonate pathway, thereby inhibiting osteoclast activation and inducing apoptosis. Preclinical studies suggest that bisphosphonates also have direct and indirect antitumor activity. In animal models, bisphosphonates reduced skeletal tumor burden and bone metastases. Currently, intravenous bisphosphonates are the standard therapy for hypercalcemia of malignancy, and they have become an integral part of the treatment of bone metastases in conjunction with standard antineoplastic agents. Intravenous bisphosphonates quickly normalize serum calcium, reduce skeletal complications, and palliate bone pain in patients with bone metastases. Intravenous pamidronate (90mg via 2-hour infusion every 3–4 weeks) has, until recently, been the international standard for the treatment of osteolytic bone lesions from breast cancer or multiple myeloma. However, 4mg zoledronic acid (via 15-minute infusion) is quickly becoming the new standard based on evidence that it is as safe and effective as 90mg pamidronate in patients with breast cancer and multiple myeloma and significantly more effective for hypercalcemia of malignancy. Consequently, the American Society of Clinical Oncology guidelines for breast cancer and multiple myeloma recommend pamidronate or zoledronic acid for patients with radiographic evidence of osteolytic bone destruction. Moreover, 4mg zoledronic acid is the only bisphosphonate that has demonstrated significant clinical benefit in patients with other solid tumors, including lung cancer, and prostate cancer patients with primarily osteoblastic bone metastases. Bisphosphonates also may have activity in the adjuvant setting to prevent or delay the development of bone metastases. Studies with oral clodronate in early breast cancer have provided clinical evidence that bone metastases can be inhibited, and the studies are ongoing with more potent bisphosphonates. Bisphosphonates have also been shown to prevent cancer treatment-induced bone loss. These and other studies continue to redefine the role of bisphosphonates in the treatment of malignant bone disease and the management of bone health in cancer patients.     

Bisphosphonates: clinical experience

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in patients with bone metastases from breast cancer, and zoledronic acid has demonstrated the broadest clinical activity in patients with a wide variety of tumor types.     

Toward new horizons: the future of bisphosphonate therapy

Bisphosphonate therapy has become a standard of care for patients with malignant bone disease. In addition, preclinical and preliminary clinical data suggest that bisphosphonates may prevent cancer-treatment-induced bone loss (CTIBL) and the development of malignant bone disease in patients with early-stage cancer. Patients who receive adjuvant hormonal therapy for breast cancer or androgen-deprivation therapy for prostate cancer are at an especially high risk for CTIBL because of reduced estrogenic signaling. Oral clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), oral risedronate (Actonel; Proctor and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and i.v. zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ) have all demonstrated promise in preventing CTIBL in patients receiving hormonal therapy for breast cancer. Zoledronic acid has demonstrated efficacy with the longest between-treatment interval (3-6 months) and is currently being investigated in the Zometa/Femara Adjuvant Synergy Trials (Z-FAST and ZO-FAST in the United States and Europe, respectively). In patients receiving androgen-deprivation therapy for prostate cancer, i.v. pamidronate (Aredia; Novartis Pharmaceuticals Corp.) and i.v. zoledronic acid both have demonstrated significant benefits over placebo, but only zoledronic acid produced significant increases in bone mineral density compared with baseline values. Additionally, bisphosphonates have demonstrated antitumor activities in preclinical models, and clinical trials with oral clodronate suggest that bisphosphonates might prevent or delay bone metastasis in patients with early-stage breast cancer. Clinical trials are investigating the effect of zoledronic acid on disease progression in patients with breast cancer, prostate cancer, and non-small cell lung cancer. The results of these clinical trials should further define the clinical benefit of bisphosphonates in the oncology setting.     

Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group.

PURPOSE: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. PATIENTS AND METHODS: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. Patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the time on trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated. RESULTS: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027). The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049). There was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated. CONCLUSION: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases.     

Bone metastases in breast cancer

Opinion statement Patients with advanced breast cancer who develop bone metastases suffer from longterm skeletal morbidity. Complications of bone metastases include pain, pathologic fractures, and spinal cord compression, which have a significant impact on the quality of life of patients. Treatment options for patients with bone metastases include surgery, radiation, and analgesics to reduce bone pain and to prevent or repair fractures. Intravenous bisphosphonates can delay the onset of bone metastasis and reduce the percentage of patients who experience skeletal complications of bone metastasis, thus reducing skeletal morbidity. For the past 6 years, pamidronate disodium (90 mg administered by 2-hour intravenous infusion) has been the treatment of choice for the prevention of skeletal complications of bone metastases in patients with breast cancer. However, a more potent bisphosphonate, zoledronic acid (4 mg administered by 15-minute intravenous infusion), was approved for use and has improved efficacy in patients with bone metastases. Because of the increased efficacy and more convenient infusion time, zoledronic acid may become the new standard of care for the treatment and prevention of skeletal complications secondary to bone metastases in patients with breast cancer. Phase III clinical trials have shown that patients with an existing skeletal complication are more likely to develop subsequent complications compared with patients who have not experienced a complication. Therefore, zoledronic acid therapy should be initiated when the patient is diagnosed with bone metastasis.     

Effect of zoledronic acid on serum angiogenic factors in patients with bone metastases

In this study we have investigated changes in circulating angiogenic factors after a single zoledronic acid intravenous infusion. Thirty consecutive patients who had histologically confirmed breast (n = 20) and lung cancer (n = 10) associated with confirmation of bone metastases were included in the study. Serum was also available from 10 healthy volunteers. Four mg of Zoledronic acid (Zometa, Novartis) was administered as a 15-min infusion in 100-ml normal saline on an outpatient basis. Venous blood for assessment of serum parameters was drawn just before the beginning of drug infusion and again at 7 and 28 days after the zoledronic acid infusion. Serum levels of VEGF and bFGF were assayed with ELISA kits. Serum VEGF and bFGF levels were not significantly different from healthy control groups (P > 0.05). However, we found that serum VEGF levels in lung cancer patients were significantly higher than in patients with breast cancer and controls (P = 0.009, and P = 0.022, respectively). We found no significant correlation between serum VEGF and bFGF levels. No statistically significant changes were seen following infusion of zoledronic acid in patients with bone metastases for both serum VEGF and bFGF levels (P > 0.05). Unlike previous studies, zoledronic acid did not appear to exert an angiogenic activity as there was no reduction of VEGF and bFGF circulating levels after zoledronic acid infusion.