部分中文泽娃灵处方资料（仅供参考）
Zevalin(泽娃灵)
Zevalin®是世界上第一个放射性标记的单克隆抗体，2002年在美国上市，被批准用于难治复发B细胞非霍奇金淋巴瘤的治疗。以Zevalin®为代表的放射免疫标志着人类对于非霍奇金淋巴瘤的治疗进入了一个新的时代，Zevalin®结合了单克隆抗体出色的靶向性和放射性同位素强大的放射治疗作用，因此可以最大程度地杀灭肿瘤细胞。

Zevalin®由放射性同位素钇90和CD20单抗组成，与其他放射性同位素相比，钇90放射纯β射线，具有更强的射线能量。同时，由于钇90不产生γ射线，对医护人员及患者家属非常安全，因此FDA批准Zevalin®可用于门诊病人，并无需隔离防护。

与当今流行的单克隆抗体治疗（如利妥昔单抗）相比，Zevalin®显示出明显的优势。随机III期临床对照研究表明，Zevalin®与利妥昔单抗（CD20单抗）相比，总完全缓解率显著提高（80％：56％），对于达到完全缓解的病人，至疾病进展时间延长了近一倍。随着研究的深入，Zevalin®将造福越来越多的淋巴瘤患者。

在北京参加会议的先灵公司专家斯托克日前向记者介绍说，新药同时利用了单克隆抗体和放射线两种手段，比单独使用抗体治疗效果更好。

B细胞淋巴瘤是淋巴细胞性白血病的一种，患者的一类免疫细胞——B细胞发生癌变，出现恶性增生，肿瘤细胞通常成团分布。

单克隆抗体是成分单一的抗体蛋白质，每种单克隆抗体能够识别肿瘤细胞表面一种特定的蛋白质，与这种“靶子”结合，触发一系列反应，导致肿瘤细胞死亡。

这种名为ZEVALIN的新药是一种放射免疫制剂，使用了专门攻击B细胞表面的CD20蛋白质分子的单克隆抗体，同时携带有放射性元素钇－90。

由于淋巴瘤细胞对放射线较为敏感，钇－90所释放的射线可以与单克隆抗体联合，形成“交叉火力”，深入肿瘤内部杀死细胞，比仅仅使用单克隆抗体杀死肿瘤更加有效。单独使用的抗体，药力难以到达肿瘤深部。

新药中的单克隆抗体只能与肿瘤细胞结合，因此能准确地把放射源带到肿瘤细胞团中。由于90％的放射能量释放在放射源周围5毫米范围内，放射线对正常组织的损害比较小。

一项临床研究表明，仅使用抗体治疗时没有疗效或疗效轻微的患者，有75％的人使用ZEVALIN后病情有明显好转，免疫系统开始恢复，血液成分逐渐转向正常。另一项143名患者参加的对照试验中，使用ZEVALIN治疗的一组，有80％的患者病情好转；而仅使用抗体、不使用放射线的一组患者，仅56％对治疗有反应。

不过，目前临床试验还不能证明ZEVALIN对高恶度B细胞淋巴瘤即侵袭性淋巴瘤也有显著疗效。

先灵公司的莫斯迈尔博士说，由于单克隆抗体比较难制取，这种新药的成本昂贵。他希望将来能找到费用低廉的高效生产技术，例如用转基因庄稼和羊奶来获取抗体。

毒副作用信息
2005年11月9日，美国FDA网站CDER网页10月28日发布消息：Biogen Idec公司与FDA共同向卫生保健专业人员通报了泽娃灵（Zevalin）处方信息中的黑框警告、警告和不良反应三项做出修改一事，修改内容中描述了采用泽娃灵治疗方案可能与出现严重的皮肤或皮肤粘膜反应有关，有些反应甚至会产生致命的后果。这些信息来自上市后的使用报告。已产生严重皮肤或皮肤粘膜反应的病人不应该继续使用Zevalin治疗方案，同时应该寻求即时的药品评价。

ZEVALIN - ibritumomab tiuxetan用药说明

频谱制药公司

最初美国批准：2002
 
适应症
Zevalin治疗是1抗CD20-导向，放射治疗抗体的Zevalin治疗治疗复发或难治性，低，高档或滤泡B细胞非霍奇金淋巴瘤，其中包括美罗华难治性滤泡性非霍奇金淋巴瘤患者（1治疗方案的一部分表示）。
 
剂量和用法
第1天：管理利妥昔单抗250 mg/m2的第四。利妥昔单抗注射后4小时内，管理5 MCI-111 Zevalin治疗四。
7，8，或9日：
管理利妥昔单抗250 mg/m2的静脉输液。

如果血小板≥150,000 / mm3的：利妥昔单抗注射后4小时内，管理0.4 MCI /公斤Y型90 Zevalin治疗四。
如果血小板≥100,000，但≤149,000 / mm3的利妥昔单抗注射后4小时内，管理0.3 MCI /公斤Y型90 Zevalin治疗四。
 
剂型和优势
每2毫升3.2毫克，单次使用小瓶。

禁忌
没有。
 
注意事项：
输液反应：立即停止和永久停止美罗华，在111 Zevalin治疗，Y型90 Zevalin治疗严重的输液反应。
长期和严重的血细胞减少：不要管理Zevalin治疗患者≥25％的淋巴瘤骨髓侵犯或受损的骨髓储备。
严重的皮肤和皮肤粘膜反应：停止美罗华，111 Zevalin治疗，Y型90 Zevalin治疗输液，如果出现严重的皮肤或粘膜反应。
继发性白血病，骨髓增生异常综合征（MDS）
embryofetal毒性：可能引起胎儿危害孕妇管理。
外渗：监视器外渗和终止输液外渗发生。在另一肢体恢复输液。
免疫：不要管理活病毒疫苗，最近收到Zevalin治疗的患者。
实验室监测：获取全血细胞计数（CBC）和血小板计数至少每周。

不良反应
最常见的不良反应（> 40％），中性粒细胞减少，血小板减少，贫血，乏力，胃肠道症状。
药物相互作用
监视器的患者接受药物干扰血小板功能或凝血的血小板减少症和出血更加频繁。
在特殊人群中使用
哺乳的母亲停止哺乳。
日期：06/2009

Zevalin (Ibritumomab Tiuxetan)

Zevalin (Ibritumomab Tiuxetan) is indicated in the treatment for follicular lymphoma, as a side treatment after inducing the remission. It is normally recommended to the patients who haven’t been through a previous treatment for such an unpleasant disease. It was also not established yet whether the drug can be used as a side treatment for chemotherapy.
Administration
Administering Zevalin (Ibritumomab Tiuxetan) is done with a high attention and care, only be a specially trained medically personnel. It is administered through a perfusion. The perfusion must be prepared according to the current safety and radiological measures.
Prior to getting this treatment, the patient must go through a similar, more powerful one – rituximab. The first day consists of an intravenous perfusion with rituximab that shouldn’t last for more than 4 hours. The doctor must administrate 250mg per square meter. The actual Zevalin (Ibritumomab Tiuxetan) treatment starts a week later. The patient will need a second 4 hours perfusion with rituximab, then an intravenous perfusion with Zevalin (Ibritumomab Tiuxetan) for 10 minutes.
According to the results, side reactions and health state of the patient, the specialist doctor may recommend a new cycle or not. There is no such thing as a maximum period for this treatment. It is taken for as long as the organism needs it.
In order to be efficient, the drug must have a radiochemical purity of over 95%.
Contraindications
This treatment is very risky if administered in an inappropriate way. If the patient presents any signs of hypersensitivity to any of the excipients of this drug, the doctor must find an alternative treatment instead.
It is also contraindicated in pregnant women. The tests on animals haven’t been conclusive enough. The same goes for nursing women. The medication can be transmitted to the baby through the milk, therefore the patient should stop nursing during the treatment.
The tests on children and old people have also proven to be unconvincing, therefore they shouldn’t take any risks at all. However, there haven’t been any major differences noticed between the young adults and the patients older than 65.
When it comes to concomitant administration with other drugs, there aren’t any known side effects, but at the same time, the tests are still ongoing.
Side effects
The radiation dose coming from this treatment can be extremely harmful for a lot of patients. Before actually involving with the Zevalin (Ibritumomab Tiuxetan) treatment, you must make sure the risks you take are worth. If they cannot outweigh the potential results, then you should probably change your mind. The side effects are severe and include infections, hemorrhages, nausea or vomiting.
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Indications and Usage
ZEVALIN® is a CD20-directed radiotherapeutic antibody administered as part of the ZEVALIN therapeutic regimen indicated for the treatment of patients with:

Relapsed or refractory, low-grade or follicular B-cell non-Hodgkin’s lymphoma (NHL).
Previously untreated follicular NHL who achieve a partial or complete response to first-line chemotherapy.
Important Safety Information
WARNING: SERIOUS INFUSION REACTIONS, PROLONGED AND SEVERE CYTOPENIAS,
and SEVERE CUTANEOUS AND MUCOCUTANEOUS REACTIONS
Serious Infusion Reactions: Deaths have occurred within 24 hours of rituximab infusion, an essential component of the ZEVALIN therapeutic regimen. These fatalities were associated with hypoxia, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Most (80%) fatalities occurred with the first rituximab infusion. Discontinue rituximab and Y-90 ZEVALIN infusions in patients who develop severe infusion reactions.

Prolonged and Severe Cytopenias: Y-90 ZEVALIN administration results in severe and prolonged cytopenias in most patients. Do not administer Y-90 ZEVALIN to patients with ≥25% lymphoma marrow involvement and/or impaired bone marrow reserve.

Severe Cutaneous and Mucocutaneous Reactions: Severe cutaneous and mucocutaneous reactions, some fatal, can occur with the ZEVALIN therapeutic regimen. Discontinue rituximab and Y-90 ZEVALIN infusions in patients experiencing severe cutaneous or mucocutaneous reactions.

Dosing: The dose of Y-90 ZEVALIN should not exceed 32.0 mCi (1184 MBq).

Leukemia and Myelodysplastic Syndrome: Among 204 patients receiving Y-90-ZEVALIN following first-line chemotherapy, two patients (1%) were diagnosed with AML within 3 years of receiving ZEVALIN.

Myelodysplastic syndrome (MDS) and/or acute myelogenous leukemia (AML) were reported in 5.2% (11/211) of patients with relapsed or refractory NHL enrolled in clinical studies and 1.5% (8/535) of patients included in the expanded-access trial, with median follow-up of 6.5 and 4.4 years, respectively. Among the 19 reported cases, the median time to diagnosis of MDS or AML was 1.9 years following treatment with the ZEVALIN therapeutic regimen; however, the cumulative incidence continues to increase.

Embryo-fetal Toxicity: May cause fetal harm if given during pregnancy.

Extravasation: Monitor for extravasation and terminate infusion if it occurs. Resume infusion in another limb.

Immunization: Do not administer live viral vaccines to patients who recently received ZEVALIN.

Laboratory Monitoring: Obtain complete blood counts (CBC) and platelet counts at least weekly.

Radionuclide Precautions: During and after radiolabeling ZEVALIN with Y-90, minimize radiation exposure to patients and to medical personnel, consistent with institutional good radiation safety practices and patient management procedures.

Creutzfeldt-Jakob Disease (CJD): The ZEVALIN therapeutic regimen contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, ZEVALIN carries an extremely remote risk for transmission of viral diseases. A theoretical risk for transmission of CJD also is considered extremely remote. No cases of transmission of viral diseases or CJD have ever been identified for albumin.

Impairment of Fertility: There is a potential risk that the ZEVALIN therapeutic regimen could cause toxic effects on the male and female gonads. Effective contraceptive methods should be used during treatment and for up to 12 months following the ZEVALIN therapeutic regimen.

Nursing Mothers: Patients should be advised to discontinue nursing during and after ZEVALIN treatment.

Adverse Reactions: The most common adverse reactions of ZEVALIN are cytopenias, fatigue, abdominal pain, nausea, nasopharyngitis, asthenia, diarrhea, cough, and pyrexia. Common adverse reactions (≥40%) in clinical trials were: neutropenia, leukopenia, thrombocytopenia, anemia, infection, asthenia, musculoskeletal symptoms, and gastrointestinal symptoms. The most serious adverse reactions of ZEVALIN are prolonged and severe cytopenias (thrombocytopenia, anemia, lymphopenia, neutropenia) and secondary malignancies.

When administered following first-line chemotherapy, grade 3/4 adverse reactions of ZEVALIN include prolonged and severe cytopenias (thrombocytopenia [51%], neutropenia [41%], leukopenia [36%], lymphopenia [18%], and anemia [5%]) and secondary malignancies. Cytopenias were more severe and more prolonged among eleven (5%) patients who received ZEVALIN after first-line fludarabine or a fludarabine-containing chemotherapy regimen as compared to patients receiving non–fludarabine-containing regimens. Grade 3/4 infections occurred in 8% of ZEVALIN-treated patients and in 2% of controls and included neutropenic sepsis (1%), bronchitis, catheter sepsis, diverticulitis, herpes zoster, influenza, lower respiratory tract infection, sinusitis, and upper respiratory tract infection.

Grade 3/4 adverse reactions of ZEVALIN in relapsed or refractory NHL patients include prolonged and severe cytopenias (thrombocytopenia [63%], neutropenia [60%], anemia [17%], and ecchymosis [<1%]) and secondary malignancies. Serious infections occurred in 3% of patients (urinary tract infection, febrile neutropenia, sepsis, pneumonia, cellulitis, colitis, diarrhea, osteomyelitis, and upper respiratory tract infection). Life-threatening infections were reported in 2% of patients (sepsis, empyema, pneumonia, febrile neutropenia, fever, and biliary stent-associated cholangitis).
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Zevalin Receives Positive CHMP Opinion in Europe for First-Line Consolidation Treatment -
Bayer Schering Pharma AG has received a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) recommending Zevalin ([90Y]-ibritumomab tiuxetan) as consolidation therapy after remission induction in previously untreated patients with follicular lymphoma in Europe.

Consolidation therapy is a treatment regimen given after a patient responds to initial first-line induction therapy (e.g. chemotherapy). The aim of consolidation therapy is to rapidly improve the quality of a patient’s response, thereby extending the response duration. Zevalin would receive marketing authorisation for all EU member states as a treatment for this indication later this year upon a favorable review by the European Commission.
Non-Hodgkin’s Lymphoma is a type of malignant disease that occurs within the lymphatic system and originates from lymphocytes. With an overall prevalence of approximately 230,000 in the European Union, it is the fifth most common cancer after breast, prostate, lung and colon cancer. Non-Hodgkin’s lymphomas can be divided into two general clinical categories: Indolent lymphomas, mainly typified as follicular lymphomas, which tend to grow relatively slowly; and aggressive lymphomas, mainly typified as diffuse large B-cell lymphomas, which grow more rapidly. Follicular lymphoma is one of the most common types of indolent Non-Hodgkin’s Lymphoma, accounting for 70% of all indolent cases.
Radioimmunotherapy is effective in patients with relapsed/refractory and newly diagnosed follicular non-Hodgkin’s lymphoma. Zevalin, which combines the tumour-targeting ability of an anti-CD20 monoclonal antibody and the tumour-destroying power of localised yttrium-90 radiation, is currently approved for adult patients with rituximab relapsed or refractory CD20-positive follicular B-cell Non-Hodgkin’s Lymphoma. The CHMP’s decision to recommend Zevalin as first line consolidation therapy is based on data from the pivotal First-Line Indolent Trial (FIT).
The objective of the FIT study was the evaluation of benefit and safety of consolidation with Zevalin in follicular lymphoma patients responding to first-line chemotherapy. The data was presented for the first time at the 49th Annual Meeting of the American Society of Hematology meeting in December 2007.
FIT Study
The Zevalin FIT study was a multinational, randomised, Phase III trial to investigate Zevalin as first-line consolidation therapy, given as a single therapeutic dose. Participants were patients with advanced (stage III or IV) follicular lymphoma who achieved a partial remission or a complete remission after receiving standard first-line chemotherapy regimens. A total of 414 patients were randomised to receive either Zevalin (250mg/m2 rituximab on day 7 and on day 0 followed on day 0 by Zevalin 0.4mCi/kg; maximal dose 32mCi) or no further treatment (control). The concept tested was whether a single infusion of Zevalin would prolong progression-free survival in patients with (minimal) residual disease.
Zevalin as first-line consolidation therapy significantly prolonged progression-free survival
Results showed that Zevalin, when used as first-line consolidation therapy, significantly prolonged time without the disease progressing (progression-free survival time) from 13.5 months (control arm) to 37 months (p<0.0001). Toxicity was primarily hematologic. Grade 3/4 infections occurred in 16 (8%) patients after Zevalin compared to 5 (2%) in the control arm.