英文药名: Bexxar(Tositumomab)

中文药名: 百克沙

品牌药生产厂家: Glaxo Smith Kline

药品介绍：
Bexxar; 治疗CD20阳性，的小囊性非霍杰金氏淋巴瘤化疗复发的病人; Corixa生产; 2003年6月批准上市Bexxar治疗非Hodgkin淋巴瘤
有关专家最近呈交于美国血液病学会(ASH)年会的研究报告表明，单克隆抗体药物Bexxar具有缓解非Hodgkin淋巴瘤(NHL)的长期效应。
 
NHL是一种起始于淋巴细胞的癌症，主要表现为非典型或癌变淋巴细胞的过量积聚，进而充塞于整个淋巴系统而抑制其它免疫细胞和血细胞的生成以及行使其正常功能。由于常规化疗和放疗往往会导致某些严重的副作用，研究人员多年来一直在探讨新型疗法，其中之一就是放射免疫治疗，即将某种放射剂与特定的抗体连接起来，后者能够和癌细胞专一性结合，因而使辐射直接作用在癌细胞上而不影响其周边的正常组织。

Bexxar正是这类新型放射免疫制剂，结合有放射性碘131，其抗体部分能够专一性与癌变了的B-淋巴细胞表面特有的蛋白CD20相结合。

近期完成的5项临床研究结果证实，Bexxar的抗NHL反应平均可持续14个月，30%的患者体内完全检测不到癌细胞，而在大约8年的随访期间这些患者中有70%以上没有复发。

BEXXAR（Tositumomab治疗和碘131 Tositumomab治疗）

BEXXAR（Tositumomab治疗）套件
BEXXAR剂量（Tositumomab治疗I-131）注射液
BEXXAR治疗（Tositumomab治疗I-131）注射液

[葛兰素史克公司]

注射，静脉滴注

最初美国批准：2003年

最近的重大变化

禁忌症去除

警告和注意事项，胚胎，胎儿毒性
 
适应症
BEXXAR（Tositumomab治疗和碘我131 Tositumomab治疗）是1抗CD20-定向放射治疗抗体治疗的患者CD20阳性，复发或难治性，低档，滤泡表示，或改变非霍奇金淋巴瘤，其中包括美罗华的难治性患者非霍奇金淋巴瘤。

基于整体回应率的BEXXAR治疗方案的有效性的测定。

不为人所知的BEXXAR生存的治疗方案的影响。

重要的限制使用

BEXXAR治疗方案只有一个单一的疗程，并表示不表示为第一线治疗。
 
剂量和用法
的BEXXAR治疗方案的剂量步骤2部分组成，7至14天后，由两部分组成的治疗步骤。
 
剂型和优势
Tositumomab治疗225毫克溶液（每毫升14毫克），单用小瓶
Tositumomab治疗35毫克溶液（每毫升14毫克），单用小瓶
碘我131 Tositumomab治疗液中含有12-18 mCi的碘-131每瓶（MCI每毫升不超过0.61在校准）和2.0-6.1毫克Tositumomab治疗每瓶（不低于每毫升0.1毫克），单用小瓶
碘我131 Tositumomab治疗解决方案，包含112-168 mCi的碘-131（不小于5.6 MCI在校准每毫升）每瓶22-61毫克Tositumomab治疗每瓶（不低于每毫升1.1毫克），单用小瓶
 
禁忌
没有
 
注意事项：
继发恶性肿瘤：血液学和非血液学中学恶性肿瘤已报告。
甲状腺功能减退症：甲状腺阻断药物管理的BEXXAR治疗方案之前需要。甲状腺功能减退症的临床证据和促甲状腺激素（TSH）水平在治疗前和此后每年的评估。
胚胎 - 胎儿毒性：政府对孕妇可引起胚胎，胎儿造成伤害，包括严重的，可能是不可逆转的，新生儿甲状腺功能减退。女性和男性的生殖潜力，应使用有效的避孕措施，以避免在治疗期间和治疗剂量为12个月后怀孕。
 
不良反应
最常见的不良反应（≥25％），中性粒细胞减少，血小板减少，贫血，感染，输液反应，乏力，发热，恶心。

在特殊人群中使用
哺乳母亲停止哺乳。

更新日期：02/2012

The BEXXAR Therapeutic Regimen,a Radioimmunotherapy for non-Hodgkin's lymphomaThe BEXXAR therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) is indicated for the treatment of patients with CD20 antigen-expressing relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin’s lymphoma, including patients with Rituximab-refractory non-Hodgkin’s lymphoma.
Determination of the effectiveness of the BEXXAR therapeutic regimen is based on overall response rates in patients whose disease is refractory to chemotherapy alone or to chemotherapy and Rituximab. The effects of the BEXXAR therapeutic regimen on survival are not known.
The BEXXAR therapeutic regimen is not indicated for the initial treatment of patients with CD20-positive non-Hodgkin’s lymphoma. The BEXXAR therapeutic regimen is intended as a single course of treatment. The safety of multiple courses of the BEXXAR therapeutic regimen, or combination of this regimen with other forms of irradiation or chemotherapy, has not been evaluated.
Hypersensitivity Reactions, Including Anaphylaxis: Serious hypersensitivity reactions, including some with fatal outcome, have been reported with the BEXXAR therapeutic regimen. Medications for the treatment of severe hypersensitivity reactions should be available for immediate use. Patients who develop severe hypersensitivity reactions should have infusions of the BEXXAR therapeutic regimen discontinued and receive medical attention (see WARNINGS in Prescribing Information).
Prolonged and Severe Cytopenias: The majority of patients who received the BEXXAR therapeutic regimen experienced severe thrombocytopenia and neutropenia. The BEXXAR therapeutic regimen should not be administered to patients with >25% lymphoma marrow involvement and/or impaired bone marrow reserve (see WARNINGS and ADVERSE REACTIONS in Prescribing Information).
Pregnancy Category X: The BEXXAR therapeutic regimen can cause fetal harm when administered to a pregnant woman.
Special Requirements: The BEXXAR therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) contains a radioactive component and should be administered only by physicians and other healthcare professionals qualified by training in the safe use and handling of therapeutic radionuclides. The BEXXAR therapeutic regimen should be administered only by physicians who are in the process of being or have been certified by GlaxoSmithKline in dose calculation and administration of the BEXXAR therapeutic regimen.
IMPORTANT SAFETY INFORMATION1
Contraindications: The BEXXAR therapeutic regimen (Tositumomab and Iodine I 131 Tositumomab) is contraindicated in patients with known hypersensitivity to murine proteins or any other component of BEXXAR.
BEXXAR is contraindicated for use in women who are pregnant.
Data regarding adverse events were primarily obtained in 230 patients with non-Hodgkin’s lymphoma enrolled in 5 clinical trials. Data from 765 patients enrolled in an expanded access program were used to supplement the characterization of delayed adverse events.
Prolonged and Severe Cytopenias: The majority of patients, 71% of 230, who received the BEXXAR therapeutic regimen, experienced severe or life-threatening (Grade 3/4) cytopenias. The most common were thrombocytopenia (53%) and neutropenia (63%). Time to nadir was 4-7 weeks, lasting approximately 30 days. Due to the variable nature of the onset of the cytopenias, complete blood counts should be obtained weekly for 10-12 weeks. More frequent monitoring is indicated in patients with evidence of moderate or more severe cytopenias. Blood counts should be monitored weekly until severe cytopenias have resolved. Sequelae included infections (45%), hemorrhage (12%), and requirement for hematological supportive care (27%).
Hypersensitivity Reactions Including Anaphylaxis: Hypersensitivity reactions, including some with fatal outcome, were reported during and following administration of the BEXXAR therapeutic regimen in 6% (14) of 230 patients. In the postmarketing setting, severe hypersensitivity reactions, including fatal anaphylaxis, have been reported. Patients who have received murine proteins should be screened for human anti-mouse antibodies (HAMA) as they may be at increased risk for serious allergic reactions.
Immunogenicity: Administration of BEXXAR may result in the development of HAMA. Of the 230 patients in the clinical studies, 220 patients were seronegative for HAMA prior to treatment, and 219 had at least 1 posttreatment HAMA value obtained. With a median observation period of 6 months, a total of 23 patients (11%) became seropositive for HAMA posttreatment. The median time of HAMA development was 6 months. The cumulative incidences of HAMA seropositivity at 6 months, 12 months, and 18 months were 6%, 17%, and 21%, respectively. The presence of HAMA may affect the toxicity and/or efficacy of in vivo diagnostic or therapeutic agents that rely on murine antibodies and may affect the accuracy of in vitro and in vivo diagnostic tests.
Secondary Leukemia, Myelodysplastic Syndrome (MDS),andSecondaryMalignancies: At a median follow-up of 29 months, 44 cases of myelodysplastic syndrome and/or secondary leukemia were reported in 995 patients enrolled in clinical studies and an expanded access program. Additional malignancies (65 cases) were also reported in 54 of the patients. Approximately half of these were nonmelanomatous skin cancers (26). The remainder, which occurred in 2 or more patients, included colorectal cancer, head and neck cancer, breast cancer, lung cancer, bladder cancer, melanoma, and gastric cancer, in order of decreasing incidence. The relative risk of developing secondary malignancies in patients receiving BEXXAR over the background rate in this population cannot be determined due to the absence of controlled studies.
Hypothyroidism: Administration of BEXXAR may result in hypothyroidism. Of the 230 patients in the clinical studies, 203 patients did not have elevated thyroid-stimulating hormones (TSH) upon study entry. Of these, 137 patients had at least 1 posttreatment TSH value available and were not taking thyroid hormonal treatment upon study entry. With a median follow-up period of 46 months, the incidence of hypothyroidism based on elevated TSH or initiation of thyroid replacement therapy in these patients was 18%, with a median time to development of hypothyroidism of 16 months. The cumulative incidences of hypothyroidism at 2 and 5 years in these 137 patients were 11% and 19%, respectively. New events have been observed up to 90 months posttreatment. Of the 765 patients in the expanded access programs, 670 patients did not have elevated TSH upon study entry. Of these, 455 patients had at least 1 posttreatment TSH value available and were not taking thyroid hormonal treatment upon study entry. With a median follow-up period of 33 months, the incidence of hypothyroidism based on elevated TSH or initiation of thyroid replacement therapy in these 455 patients was 13%, with a median time to development of hypothyroidism of 15 months. The cumulative incidences of hypothyroidism at 2 and 5 years in these patients were 9% and 17%, respectively. Thyroid-blocking medication should be prescribed as described in the prescribing information; if patients do not tolerate the medication they should not be given BEXXAR. Patients should be evaluated for signs and symptoms of hypothyroidism and screened for biochemical evidence of hypothyroidism annually.
Infusional Toxicities: Infusional toxicities including fever, rigors, chills, sweating, nausea, hypotension, dyspnea, and bronchospasm have been reported during and/or following the infusion of BEXXAR. Fever, rigors, chills, or sweating were reported in 67 patients (29%) within 14 days following the dosimetric dose. Infusional toxicities were managed by slowing and/or temporarily interrupting the infusion. Adjustments occurred in 7% of the patients and included reduction in the rate of infusion by 50%, temporary interruption of the infusion, and in 2 patients, infusion was permanently discontinued.
Assessment of Biodistribution: The biodistribution of Iodine I 131 Tositumomab should be assessed. If biodistribution is altered, the therapeutic dose should not be administered.