国产唑来膦酸治疗肿瘤高钙血症多中心Ⅱ期临床观察

目的：评价国产注射用唑来膦酸治疗肿瘤高钙血症的临床疗效和安全性。方法：采用多中心、开放临床研究对15例肿瘤性高钙血症患者给予唑来膦酸4mg静脉滴注15min治疗，在28天内定期观察血钙的变化和不良反应。结果：1例患者因依从性差出组，可评价疗效14例。有效缓解率，即校正血钙降至正常，为100％（14／14），有效缓解中位时间为5．07天，缓解的中位维持时间22．30天。不良反应主要有轻中度发热。结论：国产注射用唑来膦酸能够快速、有效、持久的降低恶性肿瘤高钙血症，使用安全、方便。     

唑来膦酸治疗癌症骨转移疼痛临床观察

目的探讨唑来膦酸治疗恶性肿瘤骨转移疼痛的疗效和安全性.方法选择恶性肿瘤骨转移中、重度疼痛患者52例,随机双盲分成两组:A组(试验组)22例:唑来膦酸4mg溶于生理盐水50ml静滴;B组(对照组)30例:博宁90mg 生理盐水750ml静滴.结果唑来膦酸镇痛效果:显效(CR):4/22,部分缓解(PR):13/22,无效(NR):5/22,总有效率(CR PR):77.27%(17/22),疗效维持时间16.4天,KPS评分平均提高20分,主要不良反应为一过性骨痛加重,发热、恶心、呕吐.对照组总有效率(RR):77.33%,疗效维持时间14.8天.结论唑来膦酸对缓解癌症骨转移疼痛有效,安全性好,病人可耐受.     

唑来膦酸治疗恶性肿瘤骨转移研究进展

骨骼是恶性肿瘤常见的转移部位之一,并可带来一系列的并发症,如骨痛、病理性骨折、脊髓压迫症和高钙血症等.二膦酸盐是治疗骨转移最常见的药物,唑来膦酸作为新一代含氮二磷酸盐类药物,是至今已发现的药物中抗骨吸收能力最强的.本文综述了唑来膦酸治疗恶性肿瘤骨转移的研究进展.     

国产唑来膦酸治疗恶性肿瘤骨转移24例临床观察

目的观察国产唑来膦酸(博来宁)治疗恶性肿瘤骨转移的临床疗效和不良反应。方法国产唑来膦酸4mg加入0.9%氯化钠溶液100ml中静脉滴注15分钟。每4周重复给药1次,3次后评价疗效。结果止痛有效率为79.2%,维持中位时间25天。活动能力改善有效率为66.7%。结论国产唑来膦酸可缓解恶性肿瘤骨转移所致疼痛,改善生活质量,且不良反应轻微,耐受性好。     

唑来膦酸注射液治疗恶性肿瘤骨转移疼痛的临床疗效观察

Objective： To evaluate the efficacy and safety of zoledronic acid for the pain caused by metastatic tumor of bone. Methods： 52 patients with metastatic tumor of bone were randomly divided into two groups. The zoledronic acid group received 4 mg zoledronic acid infusion for 30 minutes and the control group received 90 mg pamidronate infusion for 6 hours. Results： The effective rates in zoledronic acid group and control group were 73.08% and 69.23% respectively. No significant difference was observed between the two groups. The median pain relief onset at days 5 and 7, respectively, and no significant difference was observed. The ECOG scores on the 7th day after medication： the differences in the zoledronic acid group before and after medication and between the two groups were both significant （P 〈 0.001 and P = 0.0448）. The adverse reaction was no significant difference between the two groups. Conclusion： Zoledronic acid is efficient and safe in the treatment of pain caused by metastatic tumor of bone and it has low adverse reaction rate and convenient shorter using time.     

国产唑来膦酸治疗肿瘤高钙血症多中心Ⅱ期临床观察

Objective: To evaluate the effect and safety of clinical use of zoledronic acid in the treatment of malignant hypercalcemia. Methods: A multi-center, open phase Ⅱ clinical trial was conducted in 15 cases with malignant hypercalcemia who received zoledronic acid intravenously for 15 min. The level of blood calcium and side effects were recorded regularly within 28 days after injection. Results: One case was dropped out due to bad compliance. The complete response rate (the corrected serum calcium was reduced to normal level) was 100.00% (14/14). The medium time of complete response rate was 5.07 days. The medium maintain time was 22.30 days. Slight, or moderate fever was observed. Conclusion: Zoledronic acid can effectively reduce the malignant hypercalcemia. The use of zoledronic acid appears to be safety and convenient.     

注射用唑来膦酸治疗恶性肿瘤溶骨性骨转移疼痛的Ⅱ期临床试验

背景与目的:骨转移是引起恶性肿瘤患者疼痛的最常见原因,严重影响患者的生活质量。唑来膦酸是第三代的双膦酸盐类药物,能抑制破骨细胞活性,缓解疼痛。本研究观察注射用唑来膦酸单次静脉滴注治疗恶性肿瘤溶骨性骨转移疼痛的有效性和安全性。方法:采用随机双盲双模拟、阳性药平行对照、多中心的研究方法。试验组:唑来膦酸加甘露醇冻干粉针;对照组:甘露醇冻干粉针加帕米膦酸二钠。结果:2003年10月至2004年10月共随机入组216例,试验组109例,对照组107例。试验组和对照组患者用药前的疼痛强度(PI)分别为6.0±1.1和6.0±1.3(P=0.938);治疗后第7天疼痛强度分别为3.7±2.0和4.1±2.0(P=0.119);第14天分别为3.2±2.0和3.7±2.4(P=0.129)。两组完全缓解(completeresponse,CR)率10.4%和9.5%,部分缓解(partialresponse,PR)率69.8%和69.5%,总缓解率88.7%和85.7%(P>0.05);出现CR时间分别为(7.0±2.2)天和(9.5±2.6)天(P=0.033)、出现PR时间为(4.9±2.6)天和(5.0±2.5)天(P=0.908);CR的持续时间(13.2±1.8)天和(14.0±0.0)天(P=0.155),PR持续时间(13.4±1.9)天和(12.8±2.8)天(P=0.127)。试验组出现CR时间较对照组早,差异有显著性(P<0.05),其余指标两组间差异均无显著性(P>0.05)。不良反应主要是发热、恶心呕吐、乏力等,两组在不良反应发生率及程度等方面无显著性差异(P>0.05)。结论:注射用唑来膦酸治疗恶性肿瘤溶骨性骨转移疼痛的有效性和安全性与帕米膦酸二钠相似,但起效更快。     

唑来磷酸治疗恶性肿瘤引起高钙血症的临床研究

目的评价唑来磷酸（择泰）治疗恶性肿瘤引起高钙血症的有效性和安全性。方法入组患者共有17例,均为校正血钙值〉2．7mmol／L的肿瘤患者,以唑来磷酸4mg,静脉滴注15min,观察28d内的校正血钙值。结果本组17例患者均可评价疗效及安全性,有效率为94．1％（16／17）,仅1例无效。有效患者的校正血钙均值于用药后第4天第1次复查时即降至正常,于第14人达到最低点,各观察日校正血钙值与疗前比较均明显下降,差异有统汁学意义（P均〈0．01）。主要不良反应为发热（29．4％,5／17）、低钙性抽搐（11.8％,2／17）和轻度早搏（5．9％,1／17）。结论唑来磷酸治疗恶性肿瘤性高钙血症疗效确切,不良反应轻,耐受性好。     

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。     

唑来膦酸治疗骨转移癌疼痛的临床观察

目的观察唑来膦酸治疗恶性肿瘤骨转移导致疼痛的疗效及安全性。方法恶性肿瘤骨转移伴中重度疼痛患者38例,随机双盲分为A组(治疗组)20例唑来膦酸4mg溶于生理盐水50ml,静脉滴注(15min);安慰剂 生理盐水500ml,静脉滴注(4h);B组(对照组)18例安慰剂 生理盐水50ml,静脉滴注(15min);帕米膦酸二钠60mg 生理盐水500ml,静脉滴注(4h)。结果A组显效率85.0%,B组为83.4%,差异无显著性(P>0.05)。起效时间分别为5.2d与5.5d。结论唑来膦酸缓解恶性肿瘤骨转移所致疼痛有效,副作用小,患者可耐受,其有效性和安全性与帕米膦酸二钠相似。     

A multicenter and open label clinical trial of zoledronic acid 4 mg in patients with hypercalcemia of malignancy

BACKGROUND: Hypercalcemia of malignancy is a serious complication of cancer. The objective of this study was to investigate the efficacy and safety of zoledronic acid, a new-generation bisphosphonate and the most potent inhibitor of bone resorption identified to date, for hypercalcemia of malignancy in Japanese patients. METHODS: Patients with hypercalcemia of malignancy, defined as an albumin-corrected serum calcium level > or =12.0 mg/dl, were treated with a single dose of zoledronic acid, 4 mg, by 15 min infusion. Clinical end-points included the proportion of patients with complete response, which was defined as a decrease of corrected serum calcium < or =10.8 mg/dl by day 10, and time to relapse, which is defined as the duration in days between the date of infusion and last available corrected serum calcium <11.6 mg/dl. RESULTS: Twenty-seven patients were enrolled in this study and 25 patients were evaluable for the efficacy of zoledronic acid. The mean corrected serum calcium level decreased from 14.5 to 9.6 mg/dl by day 10. The complete response rate was 84%. The median time to relapse was 23 days, ranging from 0 to 56 days. The most frequently observed adverse event was fever (< or =38 degrees C). Electrolyte abnormalities suspected to be drug related including grade 3 or 4 hypocalcemia, hypophosphatemia and hypokalemia were observed in 11 patients; however, all patients were asymptomatic. No serious adverse events associated with renal toxicity were reported. CONCLUSIONS: Zoledronic acid is well tolerated and is effective for hypercalcemia of malignancy in Japanese patients.     

A phase II study of carboplatin and chronic high-dose tamoxifen in patients with recurrent malignant glioma

SummaryPurpose To determine the response rate, time to disease progression, survival, and toxicity of intravenous carboplatin and chronic oral high-dose tamoxifen in patients with recurrent malignant gliomas.Patients and methods Patients with histological confirmation of recurrent malignant gliomas were eligible for this multicenter phase II trial. Treatment consisted of 400 mg/m² carboplatin intravenously every 4 weeks and oral high dose chronic tamoxifen (80 mg bid in women and 100 mg bid in men).Results Twenty seven patients met the eligibility criteria and were evaluable for response. The histological subtypes were: 16 (59%) glioblastoma multiforme (GBM), malignant astrocytoma (5 patients), malignant mixed glioma (5 patients), and glioblastoma/gliosarcoma (1 patient). Twenty-two patients (82%) had an ECOG performance status of 0 or 1. No complete responses were observed, 4 patients (15%) achieved a partial response, and 14 patients (52%) had stable disease. Median time to progression was 3.65 months (95%CI 2.56, 4.83). Median overall survival was 14.09 months (95%CI 7.06, 19.91). One patient with a recurrent GBM had a sustained partial response and is progression free 81 months since starting treatment. Another patient with mixed malignant oligoastrocytoma also had a prolonged partial response (lasting 63 months) and is alive 84 months after treatment for recurrence. The most frequently reported grade 3 or 4 toxicities were fatigue (19%), nausea (11%) and anorexia (11%).Conclusions Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. Long-lasting periods of disease free survival in some patients (particularly those with malignant mixed oligo astrocytomas) were found.     

A multicenter phase II trial of intrathecal topotecan in patients with meningeal malignancies

To determine the therapeutic efficacy (13-week and 26-week CNS progression-free survival [PFS], response rate, and overall survival) and safety of intraventricular (IVent) topotecan in patients with neoplastic meningitis (NM), we conducted a phase II, open-label, nonrandomized, single-arm trial of IVent topotecan in patients with NM using 400 mug of topotecan IVent twice weekly for 6 weeks, followed by evaluation with imaging, cerebrospinal fluid (CSF), and physical examinations. In the absence of disease progression, patients were then treated with IVent topotecan weekly for 6 weeks, twice monthly for 4 months, and monthly thereafter. Sixty-two patients (23 males and 39 females) were enrolled from April 2001 through March 2006. Median age and KPS at enrollment were 56 (range 5-83) and 80 (range 60-100), respectively. Primary cancers included breast (19), lung (13), CNS (14), and others (16). Forty patients (65%) completed the 6-week induction period, among whom 13 (21%) had CSF clearance of malignant cells. Kaplan-Meier estimates of PFS at 13 and 26 weeks were 30% (95% confidence interval [CI], 20%-45%) and 19% (95% CI, 11%-34%). Overall median survival (50 deaths) was 15 weeks (95% CI, 13-24 weeks). The most common side effect was chemical meningitis in 32% of patients (5% grade 3); 32% experienced no drug side effects. IVent topotecan is well tolerated, but provides no added benefit over other IVent therapies. Because of its modest side effect profile, combining IVent topotecan with other IVent or systemic interventions should be considered.     

A multicenter, randomized clinical trial comparing zoledronic acid versus observation in patients with asymptomatic myeloma

BACKGROUND.

Bisphosphonates (BPs) are effective in the prevention and treatment of skeletal‐related events (SREs) in patients with symptomatic myeloma who are receiving chemotherapy. Recent data also suggest a possible antineoplastic activity of BPs. Few studies published to date have explored the role of BPs in patients with untreated, asymptomatic myeloma (AM). No data are available on the efficacy of zoledronic acid in these patients.

METHODS.

The authors conducted a prospective, multicenter, open‐label, phase 3, randomized trial comparing the administration of zoledronic acid versus simple observation in patients with AM. One‐hundred sixty‐three patients were enrolled and randomized (1:1) to receive zoledronic acid (n = 81 patients) or not to receive zoledronic acid (n = 82 patients) for 1 year at a dose of 4 mg monthly as a single, 15‐minute, intravenous infusion.

RESULTS.

After a median follow‐up of 64.7 person‐months, 44.4% of patients in the zoledronic acid group and 45.1% of the control group progressed to ‘symptomatic’ myeloma requiring chemotherapy (P = .9307). The median time to progression was 67 months and 59 months for the treatment and control groups, respectively (P = .8312). At progression, SREs were significantly lower in the zoledronic acid‐treated group (55.5%) than in the control group (78.3%; P = .041), whereas anemia, renal failure, and extramedullary disease were not statistically different. More frequent adverse events observed in the zoledronic acid‐treated group were asymptomatic hypocalcemia and fever. One patient developed reversible osteonecrosis of the jaw. No renal failure caused by zoledronic acid was reported.

CONCLUSIONS.

The monthly use of zoledronic acid for 1 year in patients with AM reduced the development of SREs at progression but did not influence the natural history of the disease. Cancer 2008. © 2008 American Cancer Society.     

Phase II trial of liposomal daunorubicin in malignant pleural mesothelioma

Background:To assess the response rate, toxicity and survival in patients with malignant pleural mesothelioma treated with liposomal daunorubicin. The study design allowed for dose escalation pending toxicity. Patients and methods:Liposomal daunorubicin (DaunoXome, Nexstar, USA) 120 mg/m² was administered every 21 days to a maximum of 6 cycles. Patients had to have histologically-proven malignant pleural mesothelioma. Patients were all chemotherapy-naïve with ECOG performance status 0–2. Results:Fourteen patients were enrolled. There were no objective or symptomatic responses though nine patients (64%) had stable disease on therapy. Myelosuppression was the major toxicity with 9 of 11 patients evaluable for toxicity experiencing grade 3 or 4 neutropenia. Other toxicities seen in at least 30% of patients included grade 3 infection and grade 2 nausea and vomiting. The median overall survival by intention-to-treat analysis was 6.1 months from the time of first treatment. The median duration of stable disease from time of first treatment for patients not progressing on therapy was 5.1 months. Conclusions:Liposomal daunorubicin 120 mg/m² has no useful clinical activity in patients with malignant pleural mesothelioma. Toxicity was substantial with most patients experiencing at least one episode of grade 3 or 4 neutropenia. Liposomal daunorubicin cannot be recommended for patients with malignant pleural mesothelioma.     

唑来膦酸钠联合89SrCl2治疗骨转移瘤的临床疗效

目的:评估89SrCl2联合唑来膦酸钠在恶性肿瘤骨转移治疗中的临床疗效。方法:95例恶性肿瘤骨转移患者随机分为三组,实验组32例应用89SrCl2联合唑来膦酸钠治疗,另外两组设为对照组,分别单纯给以89SrCl2或唑来膦酸钠治疗。随访观察6个月,根据治疗后疼痛缓解和全身骨扫描结果判断疗效。结果:实验组疼痛缓解总有效率为87.50%(28/32),对照组分别为77.42%(24/31)、75.00%(24/32)。实验组和对照组疼痛缓解改善比较差异有统计学意义(P<0.05)。实验组骨转移病灶好转或消退总有效率为34.38%（11/32）,对照组分别为32.26%（10/31）、31.25%（10/32）,实验组和对照组病灶改善比较差异无统计学差异(P>0.05)。实验组观察唑来膦酸钠的给药时间,一周内和一月后给药骨痛缓解总有效率分别为64.71%（11/17）,66.67%（10/15）,疼痛改善比较无统计学差异(P>0.05)。结论:89SrCl2联合唑来膦酸钠治疗恶性骨转移癌缓解骨痛优于单独给药。89SrCl2和唑来膦酸钠联合给药不存在拮抗和竞争,可以同时联合使用。     

The trifunctional antibody catumaxomab for the treatment of malignant ascites due to epithelial cancer: Results of a prospective randomized phase II/III trial

Malignant ascites is a common manifestation of advanced cancers, and treatment options are limited. The trifunctional antibody catumaxomab (anti‐epithelial cell‐adhesion molecule x anti‐CD3) represents a targeted immunotherapy for the intraperitoneal (i.p.) treatment of malignant ascites secondary to epithelial cancers. In this phase II/III trial (EudraCT 2004‐000723‐15; NCT00836654), cancer patients (n = 258) with recurrent symptomatic malignant ascites resistant to conventional chemotherapy were randomized to paracentesis plus catumaxomab (catumaxomab) or paracentesis alone (control) and stratified by cancer type (129 ovarian and 129 nonovarian). Catumaxomab was administered as an i.p. infusion on Days 0, 3, 7 and 10 at doses of 10, 20, 50 and 150 μg, respectively. The primary efficacy endpoint was puncture‐free survival. Secondary efficacy parameters included time to next paracentesis, ascites signs and symptoms and overall survival (OS). Puncture‐free survival was significantly longer in the catumaxomab group (median 46 days) than the control group (median 11 days) (hazard ratio = 0.254: p < 0.0001) as was median time to next paracentesis (77 versus 13 days; p < 0.0001). In addition, catumaxomab patients had fewer signs and symptoms of ascites than control patients. OS showed a positive trend for the catumaxomab group and, in a prospectively planned analysis, was significantly prolonged in patients with gastric cancer (n = 66; 71 versus 44 days; p = 0.0313). Although adverse events associated with catumaxomab were frequent, they were manageable, generally reversible and mainly related to its immunologic mode of action. Catumaxomab showed a clear clinical benefit in patients with malignant ascites secondary to epithelial cancers, especially gastric cancer, with an acceptable safety profile.