|
部份中文邦罗力处方资料（仅供参考）
2 Administration every 3 to 4 week A 15 minute infusion time has not been studied in cancer patients with CLCr <50 mL/min. Elderly population (> 65 years) No dose adjustment is required (see section 5.2). Paediatric population The safety and efficacy of Bondronat in children and adolescents below the age of 18 years have not been established. No data are available (see section 5.1 and section 5.2). Method of administration For intravenous administration. The content of the vial is to be used as follows: • Prevention of Skeletal Events - added to 100 ml isotonic sodium chloride solution or 100 ml 5% dextrose solution and infused over at least 15 minutes. See also dose section above for patients with renal impairment • Treatment of tumour-induced hypercalcaemia - added to 500 ml isotonic sodium chloride solution or 500 ml 5% dextrose solution and infused over 2 hours For single use only. Only clear solution without particles should be used. Bondronat concentrate for solution for infusion should be administered as an intravenous infusion. Care must be taken not to administer Bondronat concentrate for solution for infusion via intra-arterial or paravenous administration, as this could lead to tissue damage.. 4.3 Contraindications - Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 - Hypocalcaemia 4.4 Special warnings and precautions for use Patients with disturbances of bone and mineral metabolism Hypocalcaemia and other disturbances of bone and mineral metabolism should be effectively treated before starting Bondronat therapy for metastatic bone disease. Adequate intake of calcium and vitamin D is important in all patients. Patients should receive supplemental calcium and/or vitamin D if dietary intake is inadequate. Anaphylactic reaction/shock Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with IV ibandronic acid. Appropriate medical support and monitoring measures should be readily available when Bondronat intravenous injection is administered. If anaphylactic or other severe hypersensitivity/allergic reactions occur, immediately discontinue the injection and initiate appropriate treatment. Osteonecrosis of the jaw Osteonecrosis of the jaw (ONJ) has been reported very rarely in the post marketing setting in patients receiving Bondronat for oncology indications (see section 4.8). The start of treatment or of a new course of treatment should be delayed in patients with unhealed open soft tissue lesions in the mouth. A dental examination with preventive dentistry and an individual benefit-risk assessment is recommended prior to treatment with Bondronat in patients with concomitant risk factors. The following risk factors should be considered when evaluating a patient's risk of developing ONJ: - Potency of the medicinal product that inhibit bone resorption (higher risk for highly potent compounds), route of administration (higher risk for parenteral administration) and cumulative dose of bone resorption therapy - Cancer, co-morbid conditions (e.g. anaemia, coagulopathies, infection), smoking - Concomitant therapies: corticosteroids, chemotherapy, angiogenesis inhibitors, radiotherapy to head and neck - Poor oral hygiene, periodontal disease, poorly fitting dentures, history of dental disease, invasive dental procedures e.g. tooth extractions All patients should be encouraged to maintain good oral hygiene, undergo routine dental check-ups, and immediately report any oral symptoms such as dental mobility, pain or swelling, or non-healing of sores or discharge during treatment with Bondronat. While on treatment, invasive dental procedures should be performed only after careful consideration and be avoided in close proximity to Bondronat administration. The management plan of the patients who develop ONJ should be set up in close collaboration between the treating physician and a dentist or oral surgeon with expertise in ONJ. Temporary interruption of Bondronat treatment should be considered until the condition resolves and contributing risk factors are mitigated where possible. Osteonecrosis of the external auditory canal Osteonecrosis of the external auditory canal has been reported with bisphosphonates, mainly in association with long-term therapy. Possible risk factors for osteonecrosis of the external auditory canal include steroid use and chemotherapy and/or local risk factors such as infection or trauma. The possibility of osteonecrosis of the external auditory canal should be considered in patients receiving bisphosphonates who present with ear symptoms including chronic ear infections. Atypical fractures of the femur Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, primarily in patients receiving long-term treatment for osteoporosis. These transverse or short oblique fractures can occur anywhere along the femur from just below the lesser trochanter to just above the supracondylar flare. These fractures occur after minimal or no trauma and some patients experience thigh or groin pain, often associated with imaging features of stress fractures, weeks to months before presenting with a completed femoral fracture. Fractures are often bilateral; therefore the contralateral femur should be examined in bisphosphonate-treated patients who have sustained a femoral shaft fracture. Poor healing of these fractures has also been reported. Discontinuation of bisphosphonate therapy in patients suspected to have an atypical femur fracture should be considered pending evaluation of the patient, based on an individual benefit risk assessment. During bisphosphonate treatment patients should be advised to report any thigh, hip or groin pain and any patient presenting with such symptoms should be evaluated for an incomplete femur fracture. Patients with renal impairment Clinical studies have not shown any evidence of deterioration in renal function with long term Bondronat therapy. Nevertheless, according to clinical assessment of the individual patient, it is recommended that renal function, serum calcium, phosphate and magnesium should be monitored in patients treated with Bondronat (see section 4.2). Patients with hepatic impairment As no clinical data are available, dose recommendations cannot be given for patients with severe hepatic insufficiency (see section 4.2). Patients with cardiac impairment Overhydration should be avoided in patients at risk of cardiac failure. Patients with known hypersensitivity to other bisphosphonates Caution is to be taken in patients with known hypersensitivity to other bisphosphonates. Excipients with known effect Bondronat is essentially sodium free. 4.5 Interaction with other medicinal products and other forms of interaction Metabolic interactions are not considered likely, since ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and has been shown not to induce the hepatic cytochrome P450 system in rats (see section 5.2). Ibandronic acid is eliminated by renal excretion only and does not undergo any biotransformation. Caution is advised when bisphosphonates are administered with aminoglycosides, since both substances can lower serum calcium levels for prolonged periods. Attention should also be paid to the possible existence of simultaneous hypomagnesaemia. 4.6 Fertility, pregnancy and lactation Pregnancy There are no adequate data from the use of ibandronic acid in pregnant women. Studies in rats have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Therefore, Bondronat should not be used during pregnancy. Breast-feeding It is not known whether ibandronic acid is excreted in human milk. Studies in lactating rats have demonstrated the presence of low levels of ibandronic acid in the milk following intravenous administration. Bondronat should not be used during breast-feeding. Fertility There are no data on the effects of ibandronic acid in humans. In reproductive studies in rats by the oral route, ibandronic acid decreased fertility. In studies in rats using the intravenous route, ibandronic acid decreased fertility at high daily doses (see section 5.3). 4.7 Effects on ability to drive and use machines On the basis of the pharmacodynamic and pharmacokinetic profile and reported adverse reactions, it is expected that Bondronat has no or negligible influence on the ability to drive and use machines. 4.8 Undesirable effects Summary of the safety profile The most serious reported adverse reactions are anaphylactic reaction/shock, atypical fractures of the femur, osteonecrosis for the jaw and ocular inflammation (see paragraph “description of selected adverse reactions”and section 4.4). Treatment of tumour induced hypercalcaemia is most frequently associated with a rise in body temperature. Less frequently, a decrease in serum calcium below normal range (hypocalcaemia) is reported. In most cases no specific treatment was required and the symptoms subsided after a couple of hours/days. In the prevention of skeletal events in patients with breast cancer and bone metastases, treatment is most frequently associated with asthenia followed by rise in body temperature and headache. Tabulated list of adverse reactions Table 1 lists adverse drug reactions from the pivotal phase III studies (Treatment of tumour induced hypercalcaemia: 311 patients treated with Bondronat 2 mg or 4 mg; Prevention of skeletal events in patients with breast cancer and bone metastases: 152 patients treated with Bondronat 6 mg), and from post-marketing experience. Adverse reactions are listed according to MedDRA system organ class and frequency category. Frequency categories are defined using the following convention: very common (≥1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 1 Adverse Reactions Reported for Intravenous Administration of Bondronat System Organ Class Common Uncommon Rare Very rare Not known Infections and infestations Infection Cystitis, vaginitis, oral candidiasis Neoplasms benign, malignant and unspecified Benign skin neoplasm Blood and lymphatic system disorders Anaemia, blood dyscrasia Immune system disorders Hypersensitivity†, bronchospasm†, angioedema†, anaphylactic reaction/shock†** Asthma exacerbation Endocrine disorders Parathyroid disorder Metabolism and nutrition disorders Hypocalcaemia** Hypophosphataemia Psychiatric disorders Sleep disorder, anxiety, affection lability Nervous system disorders Headache, dizziness, dysgeusia (taste perversion) Cerebrovascular disorder, nerve root lesion, amnesia, migraine, neuralgia, hypertonia, hyperaestesia, paraesthesia circumoral, parosmia Eye disorders Cataract Ocular inflammation†** Ear and labyrinth disorders Deafness Cardiac disorders Bundle branch block Myocardial ischaemia, cardiovascular disorder, palpitations Respiratory, thoracic, and mediastinal disorders Pharyngitis Lung oedema, stridor Gastrointestinal disorders Diarrhoea, vomiting, dyspepsia, gastrointestinal pain, tooth disorder Gastroenteritis, gastritis, mouth ulceration, dysphagia, cheilitis Hepatobiliary disorders Cholelithiasis Skin and subcutaneous tissue disorders Skin disorder, ecchymosis Rash, alopecia Stevens-Johnson Syndrome†, Erythema Multiforme†, Dermatitis Bullous† Musculoskeletal and connective tissue disorders Osteoarthritis, myalgia, arthralgia, joint disorder, bone pain Atypical subtrochanteric and diaphyseal femoral fractures† Osteonecrosis of jaw†** Osteonecrosis of the external auditory canal (bisphosphonate class adverse reaction)† Renal and urinary disorders Urinary retention, renal cyst Reproductive system and breast disorders Pelvic pain General disorders and administration site conditions Pyrexia, influenza-like illness**, oedema peripheral, asthenia, thirst Hypothermia Investigations Gamma-GT increased, creatinine increased Blood alkaline phosphatase increase, weight decrease Injury, poisoning and procedural complications Injury, injection site pain ee further information below Identified in post-marketing experience. Description of selected adverse reactions Hypocalcaemia Decreased renal calcium excretion may be accompanied by a fall in serum phosphate levels not requiring therapeutic measures. The serum calcium level may fall to hypocalcaemic values. Influenza-like illness A flu-like syndrome consisting of fever, chills, bone and/or muscle ache-like pain has occurred. In most cases no specific treatment was required and the symptoms subsided after a couple of hours/days. Osteonecrosis of jaw Cases of osteonecrosis of the jaw have been reported, predominantly in cancer patients treated with medicinal products that inhibit bone resorption, such as ibandronic acid (see section 4.4.) Cases of ONJ have been reported in the post marketing setting for ibandronic acid. Ocular inflammation Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with ibandronic acid. In some cases, these events did not resolve until the ibandronic acid was discontinued. Anaphylactic reaction/shock Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with intravenous ibandronic acid. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions (see details below). Ireland HPRA Pharmacovigilance Earlsfort Terrace IRL - Dublin 2 Tel: +353 1 6764971 Fax: +353 1 6762517 Website: www.hpra.ie e-mail:medsafety@hpra.ie Malta ADR Reporting Website: www.medicinesauthority.gov.mt/adrportal United Kingdom Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard 4.9 Overdose Up to now there is no experience of acute poisoning with Bondronat concentrate for solution for infusion. Since both the kidney and the liver were found to be target organs for toxicity in preclinical studies with high doses, kidney and liver function should be monitored. Clinically relevant hypocalcaemia should be corrected by intravenous administration of calcium gluconate. 5. Pharmacological properties 5.1 Pharmacodynamic properties Pharmaco-therapeutic group: Medicinal products for treatment of bone diseases, bisphosphonate, ATC Code: M05BA06. Ibandronic acid belongs to the bisphosphonate group of compounds which act specifically on bone. Their selective action on bone tissue is based on the high affinity of bisphosphonates for bone mineral. Bisphosphonates act by inhibiting osteoclast activity, although the precise mechanism is still not clear. In vivo, ibandronic acid prevents experimentally-induced bone destruction caused by cessation of gonadal function, retinoids, tumours or tumour extracts. The inhibition of endogenous bone resorption has also been documented by 45Ca kinetic studies and by the release of radioactive tetracycline previously incorporated into the skeleton. At doses that were considerably higher than the pharmacologically effective doses, ibandronic acid did not have any effect on bone mineralisation. Bone resorption due to malignant disease is characterised by excessive bone resorption that is not balanced with appropriate bone formation. Ibandronic acid selectively inhibits osteoclast activity, reducing bone resorption and thereby reducing skeletal complications of the malignant disease. Clinical studies in the treatment of tumour-induced hypercalcaemia Clinical studies in hypercalcaemia of malignancy demonstrated that the inhibitory effect of ibandronic acid on tumour-induced osteolysis, and specifically on tumour-induced hypercalcaemia, is characterised by a decrease in serum calcium and urinary calcium excretion. In the dose range recommended for treatment, the following response rates with the respective confidence intervals have been shown in clinical trials for patients with baseline albumin-corrected serum calcium ≥ 3.0 mmol/l after adequate rehydration.
Clinical studies in the prevention of skeletal events in patients with breast cancer and bone metastases Clinical studies in patients with breast cancer and bone metastases have shown that there is a dose dependent inhibitory effect on bone osteolysis, expressed by markers of bone resorption, and a dose dependent effect on skeletal events. Prevention of skeletal events in patients with breast cancer and bone metastases with Bondronat 6 mg administered intravenously was assessed in one randomized placebo controlled phase III trial with a duration of 96 weeks. Female patients with breast cancer and radiologically confirmed bone metastases were randomised to receive placebo (158 patients) or 6 mg Bondronat (154 patients). The results from this trial are summarised below. Primary efficacy endpoints The primary endpoint of the trial was the skeletal morbidity period rate (SMPR). This was a composite endpoint which had the following skeletal related events (SREs) as sub-components: - radiotherapy to bone for treatment of fractures/impending fractures - surgery to bone for treatment of fractures - vertebral fractures - non-vertebral fractures The analysis of the SMPR was time-adjusted and considered that one or more events occurring in a single 12 week period could be potentially related. Multiple events were therefore counted only once for the purposes of the analysis. Data from this study demonstrated a significant advantage for intravenous Bondronat 6 mg over placebo in the reduction in SREs measured by the time-adjusted SMPR (p=0.004). The number of SREs was also significantly reduced with Bondronat 6 mg and there was a 40% reduction in the risk of a SRE over placebo (relative risk 0.6, p = 0.003). Efficacy results are summarised in Table 2. Table 2 Efficacy Results (Breast Cancer Patients with Metastatic Bone Disease)
A statistically significant improvement in bone pain score was shown for intravenous Bondronat 6 mg compared to placebo. The pain reduction was consistently below baseline throughout the entire study and accompanied by a significantly reduced use of analgesics. The deterioration in Quality of Life was significantly less in Bondronat treated patients compared with placebo. A tabular summary of these secondary efficacy results is presented in Table 3. Table 3 Secondary Efficacy Results (Breast cancer Patients with Metastatic Bone Disease)
There was a marked depression of urinary markers of bone resorption (pyridinoline and deoxypyridinoline) in patients treated with Bondronat that was statistically significant compared to placebo. In a study in 130 patients with metastatic breast cancer the safety of Bondronat infused over 1 hour or 15 minutes was compared. No difference was observed in the indicators of renal function. The overall adverse event profile of ibandronic acid following the 15 minute infusion was consistent with the known safety profile over longer infusion times and no new safety concerns were identified relating to the use of a 15 minute infusion time. A 15 minute infusion time has not been studied in cancer patients with a creatinine clearance of <50ml/min. Paediatric population (see section 4.2 and section 5.2) The safety and efficacy of Bondronat in children and adolescents below the age of 18 years have not been established. No data are available. 5.2 Pharmacokinetic properties After a 2 hour infusion of 2, 4 and 6 mg ibandronic acid pharmacokinetic parameters are dose proportional. Distribution After initial systemic exposure, ibandronic acid rapidly binds to bone or is excreted into urine. In humans, the apparent terminal volume of distribution is at least 90 l and the amount of dose reaching the bone is estimated to be 40-50% of the circulating dose. Protein binding in human plasma is approximately 87% at therapeutic concentrations, and thus interaction with other medicinal products, due to displacement is unlikely. Biotransformation There is no evidence that ibandronic acid is metabolized in animals or humans. Elimination The range of observed apparent half-lives is broad and dependent on dose and assay sensitivity, but the apparent terminal half-life is generally in the range of 10-60 hours. However, early plasma levels fall quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration respectively. No systemic accumulation was observed when ibandronic acid was administered intravenously once every 4 weeks for 48 weeks to patients with metastatic bone disease. Total clearance of ibandronic acid is low with average values in the range 84-160 ml/min. Renal clearance (about 60 ml/min in healthy postmenopausal females) accounts for 50-60% of total clearance and is related to creatinine clearance. The difference between the apparent total and renal clearances is considered to reflect the uptake by bone. The secretory pathway of renal elimination does not appear to include known acidic or basic transport systems involved in the excretion of other active substances In addition, ibandronic acid does not inhibit the major human hepatic P450 isoenzymes and does not induce the hepatic cytochrome P450 system in rats. Pharmacokinetics in special populations Gender Bioavailability and pharmacokinetics of ibandronic acid are similar in both men and women. Race There is no evidence for clinically relevant interethnic differences between Asians and Caucasians in ibandronic acid disposition. There are only very few data available on patients with African origin. Patients with renal impairment Exposure to ibandronic acid in patients with various degrees of renal impairment is related to creatinine clearance (CLcr). In subjects with severe renal impairment (mean estimated CLcr = 21.2 mL/min), dose-adjusted mean AUC0-24h was increased by 110% compared to healthy volunteers. In clinical pharmacology trial WP18551, after a single dose intravenous administration of 6 mg (15 minutes infusion), mean AUC0-24 increased by 14% and 86%, respectively, in subjects with mild (mean estimated CLcr=68.1 mL/min) and moderate (mean estimated CLcr=41.2 mL/min) renal impairment compared to healthy volunteers (mean estimated CLcr=120 mL/min). Mean Cmax was not increased in patients with mild renal impairment and increased by 12% in patients with moderate renal impairment. For patients with mild renal impairment (CLcr ≥50 and <80 mL/min) no dosage adjustment is necessary. For patients with moderate renal impairment (CLcr ≥30 and <50 mL/min) or severe renal impairment (CLcr <30 mL/min) being treated for the prevention of skeletal events in patients with breast cancer and metastatic bone disease an adjustment in the dose is recommended (see section 4.2). Patients with hepatic impairment (see section 4.2) There are no pharmacokinetic data for ibandronic acid in patients who have hepatic impairment. The liver has no significant role in the clearance of ibandronic acid since it is not metabolized but is cleared by renal excretion and by uptake into bone. Therefore dosage adjustment is not necessary in patients with hepatic impairment. Further, as protein binding of ibandronic acid is approximately 87% at therapeutic concentrations, hypoproteinaemia in severe liver disease is unlikely to lead to clinically significant increases in free plasma concentration. Elderly (see section 4.2) In a multivariate analysis, age was not found to be an independent factor of any of the pharmacokinetic parameters studied. As renal function decreases with age, this is the only factor that should be considered (see renal impairment section). Paediatric population (see section 4.2 and section 5.1) There are no data on the use of Bondronat in patients less than 18 years old. 5.3 Preclinical safety data Effects in non-clinical studies were observed only at exposures sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. As with other bisphosphonates, the kidney was identified to be the primary target organ of systemic toxicity. Mutagenicity/Carcinogenicity: No indication of carcinogenic potential was observed. Tests for genotoxicity revealed no evidence of effects on genetic activity for ibandronic acid. Reproductive toxicity: No evidence of direct foetal toxicity or teratogenic effects were observed for ibandronic acid in intravenously treated rats and rabbits. In reproductive studies in rats by the oral route, effects on fertility consisted of increased preimplantation losses at dose levels of 1 mg/kg/day and higher. In reproductive studies in rats by the intravenous route, ibandronic acid decreased sperm counts at doses of 0.3 and 1 mg/kg/day and decreased fertility in males at 1 mg/kg/day and in females at 1.2 mg/kg/day. Adverse effects of ibandronic acid in reproductive toxicity studies in the rat were those expected for this class of medicinal products (bisphosphonates). They include a decreased number of implantation sites, interference with natural delivery (dystocia), an increase in visceral variations (renal pelvis ureter syndrome) and teeth abnormalities in F1 offspring in rats. 6. Pharmaceutical particulars 6.1 List of excipients Sodium chloride Acetic acid (99%) Sodium acetate Water for injections 6.2 Incompatibilities To avoid potential incompatibilities Bondronat concentrate for solution for infusion should only be diluted with isotonic sodium chloride solution or 5% glucose solution. Bondronat should not be mixed with calcium containing solutions. 6.3 Shelf life 5 years After econstitution: 24 hours. 6.4 Special precautions for storage This medicinal product does not require any special storage conditions prior to reconstitution. After reconstitution: Store at 2 °C – 8 °C (in a refrigerator). From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and validated aseptic conditions. 6.5 Nature and contents of container Bondronat is supplied as packs containing 1, 5 and 10 vials (6 ml type I glass vial with a bromobutyl rubber stopper). Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Any unused medicinal product or waste material should be disposed of in accordance with local requirements. The release of pharmaceuticals in the environment should be minimized. 7. Marketing authorisation holder Roche Registration Limited 6 Falcon Way Shire Park Welwyn Garden City AL7 1TW United Kingdom 8. Marketing authorisation number(s) EU/1/96/012/011 EU/1/96/012/012 EU/1/96/012/013 9. Date of first authorisation/renewal of the authorisation Date of first authorisation: 25 June 1996 Date of latest renewal: 25 June 2006 10. Date of revision of the text 25 April 2016 Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu. 附：Bondronat 2mg Concentrate for solution for infusion（http://www.medicines.org.uk/emc/medicine/8600） 第三代双膦酸盐伊班膦酸(邦罗力)研究新进展 骨是恶性肿瘤常见的转移部位,据统计,最常发生骨转移的原发肿瘤为乳腺癌和前列腺癌,发生率高达65%~75%,其次为甲状腺癌60%、肺癌30%~40%和肾癌20%~25%。肿瘤骨转移可引起骨痛、病理性骨折、高钙血症、神经根压迫、脊髓压迫等一系列并发症,严重影响患者的生活质量。双膦酸盐是目前肿瘤骨转移引起的相关性骨病的标准治疗方法。 今年3月22-24日在瑞士达沃斯举行的双膦酸盐全球论坛上,有关第三代双膦酸盐-伊班膦酸(邦罗力)的最新研究进展颇引人注目,其中双膦酸盐的肾脏安全性研究是最受关注的话题之一 。美国学者Lucia Antr?觓s等人进行的邦罗力、唑来膦酸治疗多发性骨髓瘤(MM)患者肾脏安全性的回顾性研究在这方面做了有益的尝试。 肾脏损害是MM常见的临床表现之一,在应用双膦酸盐治疗MM患者的转移性骨病时应尤其注意预防肾脏毒性,尽管目前临床常用的双膦酸盐都能预防骨骼事件的发生,但在药物肾脏安全性方面存在差异,因此选择安全性较好的药物是治疗关键。这项邦罗力、唑来膦酸肾脏安全性的比较研究始于2001年5月,至2005年12月结束,历时4年多,共入组84例MM患者,入选标准为: ● ≥18岁 ● 临床积极治疗中 ● 确诊为MM ● 静脉用唑来膦酸(4 mg)或邦罗力(6 mg)≥1次 ● 双膦酸盐治疗前后检测血清肌酐(Scr)≥1次 84例患者分别接受唑来膦酸单药(n=47)、邦罗力单药(n=15)、或先后接受唑来膦酸和邦罗力治疗(两药应用间隔至少28天,n=22),疗程1年。研究将患者分为邦罗力组(n=37)和唑来膦酸组(n=69)。 研究比较了患者接受双膦酸盐治疗前后肾小球率过滤(GFR)和血清肌酐(Scr)水平,肾脏损害定义为: ● Scr水平升高≥0.5 mg/dl(治疗前Scr<1.4 mg/dl)或升高≥1.0 mg/dl(治疗前Scr≥1.4 mg/dl) ● GFR较治疗前降低≥25% 研究数据单变量分析显示,MM患者接受邦罗力治疗后发生肾脏损害的百分比远远低于唑来膦酸治疗的MM患者(图1),唑来膦酸组患者肾脏损害风险几乎是邦罗力组患者的3倍(Scr RR 3.5, P=0.0036; GFR RR 2.6, P=0.0002)。唑来膦酸组肾脏损害的发生率(单个病人每年的肾脏不良反应事件)显著高于邦罗力组(图2)。 在接受邦罗力治疗的37例患者中进行亚组分析,结果证实既往接受过唑来膦酸治疗的患者更容易发生肾脏不良事件(Scr RR 6.1,P=0.023;GFR RR 2.4,P=0.029)。先接受唑来膦酸治疗的患者在接受邦罗力治疗期间Scr有下降的趋势,而同样的患者在接受唑来磷酸治疗时Scr水平呈现相反的上升趋势(图3)。 这项研究的结果证实,唑来膦酸与邦罗力相比显著增加MM患者肾脏损害的风险和发生率,尽管这一结果仍需要前瞻性随机对照研究进一步证实,但对临床医师选择双膦酸盐药物,了解其安全性差异仍有借鉴作用。 这届会议还介绍了有关邦罗力负荷剂量缓解骨转移性疼痛的研究进展。瑞士Roger von Moos等专家介绍了6例晚期转移性骨病患者应用负荷剂量邦罗力的疗效,证实邦罗力负荷量(6mg qd×3天)可迅速缓解骨痛,值得注意的是负荷剂量不会引起肾功能损害或其他不良反应。希腊Vassilios Vassiliou教授总结了45例转移性骨病患者的治疗情况,证实邦罗力联合放疗能有效治疗各种成骨性或破骨性骨转移,负荷剂量邦罗力(6 mg qd×3天)强化治疗后标准剂量(6 mg q3w-q4w)维持可显著缓解转移性骨痛。如果进一步的随机对照试验能证实上述临床观察结果,邦罗力负荷剂量将有可能成为转移性骨痛的标准用法。 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
