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ABRAXANE注射用紫杉醇(白蛋白结合型)—全球唯一乳腺癌靶向化疗药物
ABRAXANE注射用紫杉醇(白蛋白结合型)—全球唯一应用白蛋白纳米微粒技术生产的靶向化疗药物，适用于治疗联合化疗失败的转移性乳腺癌或辅助化疗后6个月内复发的乳腺癌。ABRAXANE注射用紫杉醇(白蛋白结合型)由美国著名的阿博利斯公司生产，2005年在美国上市，2009年进入中国，目前已在全球超过35个国家上市。
注射用紫杉醇(白蛋白结合型)的靶向治疗机理
ABRAXANE注射用紫杉醇(白蛋白结合型)是由一个个的白蛋白结合紫杉醇纳米微粒构成，这些微粒只有人体红细胞的1/100大小，外层被白蛋白包裹，内核为不溶于水的细胞毒药物。众所周知，肿瘤细胞在人体内大肆生长需要汲取足够的营养，因此肿瘤细胞会分泌一种SPARC蛋白汲取细胞间质中的蛋白质。这时，白蛋白结合紫杉醇纳米微粒通过SPARC蛋白吸附在肿瘤细胞上，并最终进入肿瘤细胞，释放出细胞毒药物，杀死肿瘤细胞，达到靶向治疗的目的。
与“饿死”肿瘤的方法相比，ABRAXANE注射用紫杉醇(白蛋白结合型)把白蛋白结合型紫杉醇优先供应给肿瘤细胞，让紫杉醇更好与之接触，导致肿瘤细胞死亡，起效更为快捷。
注射用紫杉醇(白蛋白结合型)的疗效及安全性
在对中国转移性乳腺癌患者进行的注射用紫杉醇（白蛋白结合型）与溶剂型紫杉醇随机对照II期临床试验表明：ABRAXANE注射用紫杉醇（白蛋白结合型）比溶剂型紫杉醇总有效率明显提高，该结果与对欧美地区患者所进行的全球三期临床试验的结果相一致。与溶剂型紫杉醇相比，
ABRAXANE注射用紫杉醇（白蛋白结合型）使总有效率提高接近一倍，而且中位至肿瘤进展时间也比溶剂型紫杉醇延长，达到7.6个月。与溶剂型紫杉醇相比，ABRAXANE注射用紫杉醇（白蛋白结合型）的无进展生存期也提高了26%。同时，两种治疗的最常见毒性反应相似且都是可接受的，严重不良事件的发生率基本相当，且都具有良好的耐受性。
美国休斯敦米歇尔（Michael）等进行的一项Ⅱ期临床试验显示，注射用紫杉醇（白蛋白结合型）治疗铂敏感的复发性卵巢癌、腹膜癌或输卵管癌有效且患者耐受性良好。该研究共纳入47例组织学或细胞学确诊的卵巢、输卵管或腹膜上皮癌患者，在21天治疗周期中的第1天给予30分钟静脉nab-紫杉醇260mg/m2治疗，共6个周期或直到疾病进展。
结果显示，在44例可评估者中，客观有效率（ORR）为64%，中位至缓解时间为1.3个月，中位PFS期为8.5个月，最常见的3至4级治疗相关毒性反应为中性粒细胞减少（24%）和神经病变（9%）。
注射用紫杉醇(白蛋白结合型)使用更方便
由于传统的紫杉醇类药物在使用中需要聚乙烯蓖麻油作为溶剂才能进行注射，而为了预防溶剂带来的过敏反应，患者需要在化疗前进行预防用药，使用抗阻胺及地塞米松等药物，而最新上市的注射用紫杉醇(白蛋白结合型)无需使用溶剂，因此输注时间更短，与溶剂型紫杉醇的3个小时相比，该药物仅需30分钟输注，并且给药前无需抗过敏预防用药，即可降低与溶剂相关的过敏反应的潜在风险。因此，注射用紫杉醇(白蛋白结合型)极大方便了患者的使用。
ABRAXANE Rx
Generic Name and Formulations:
Paclitaxel [bound to albumin (human)] 100mg/vial; pwd for IV infusion after reconstitution; solvent-free.
Company:
Celgene Corp
Indications for ABRAXANE:
Treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy (prior therapy should have included an anthracycline unless clinically contraindicated).
Adult Dose for ABRAXANE:
Do not treat if neutrophil count <1,500 cells/mm3 or platelets <100,000 cells/mm3. 260mg/m2 by IV infusion over 30 minutes every 3 weeks. If severe neutropenia (neutrophil <500 cells/mm3 for ≥1week) or severe sensory neuropathy occurs: reduce subsequent doses to 220mg/m2; reduce to 180mg/m2 if severe neutropenia or sensory neuropathy recurs. If grade 3 sensory neuropathy occurs, suspend use until resolution to grade 1 or 2; reduce subsequent doses. Hepatic impairment: see full labeling. Avoid extravasation.
Children's Dose for ABRAXANE:
Not evaluated.
Pharmacological Class:
Taxane antimicrotubule.
Contraindications:
Baseline neutrophil count <1,500 cells/mm3. Prior severe hypersensitivity reaction (do not rechallenge).
Warnings/Precautions:
Do not substitute for, or with, other paclitaxel products (due to formulation differences). Do frequent complete blood cell counts. Monitor for sensory neuropathy, sepsis, or pneumonitis. Hepatic or renal dysfunction. Contains human albumin; remote risk of viral transmission. Use appropriate contraception (men and women). Pregnancy (Cat.D), nursing mothers: not recommended.
Interactions:
May potentiate or be potentiated by CYP2C8 and/or CYP3A4 inducers (eg, rifampin, carbamazepine, phenytoin, efavirenz, nevirapine) and/or inhibitors (eg, ketoconazole, other imidazole antifungals, erythromycin, fluoxetine, gemfibrozil, cimetidine, ritonavir, saquinavir, indinavir, nelfinavir).
Adverse Reactions:
Bone marrow suppression (eg, neutropenia, anemia), infections, alopecia, sensory neuropathy (may require dose reduction or interruption), peripheral neuropathy, GI upset, mucositis, fatigue/asthenia, myalgia/arthralgia, abnormal ECG; alkaline phosphatase or AST elevation; dyspnea, edema, hypotension, rash (may be serious); rare: thrombotic events.
Metabolism:
Hepatic (CYP2C8, 3A4).
Elimination:
Renal, fecal.
Generic Availability:
NO
How Supplied:
Single-use vial—1
其它不良反应参见药品说明书。
【贮藏】含药物的药瓶放在原装盒中，室温（20～25℃）条件下避光保存。
【包装】玻璃瓶装，每盒一瓶。
ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine.
Important Safety Information
WARNING – NEUTROPENIA
Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug's functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS
Neutrophil Counts
ABRAXANE should not be used in patients who have baseline neutrophil counts of <1500 cells/mm3
Hypersensitivity
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
Hematologic Effects
Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 38% of patients with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to dosing on Days 1, 8, and 15 for pancreatic cancer
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm3 or platelets are less than 50,000 cells/mm3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm3 or platelet count is less than 100,000 cells/mm3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended
Nervous System
Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 followed by a dose reduction for all subsequent courses of ABRAXANE
Sepsis
Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥1500 cells/mm3, then resume treatment at reduced dose levels
Pneumonitis
Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis
Hypersensitivity
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions, have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Hepatic Impairment
Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with caution
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate or severe hepatic impairment
Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D
ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men
Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS
Among the most common (≥ 20%) adverse reactions in the phase III study, those with a ≥ 5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a ≥ 2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a ≥ 1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%), and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a ≥ 5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a ≥ 2% higher incidence for Grade 3-4 toxicity in the Abraxane/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations
Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS
Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric
The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric
Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of the pancreas
Renal Impairment
The use of ABRAXANE has not been studied in patients with renal impairment
DOSAGE AND ADMINISTRATION
Withhold ABRAXANE if bilirubin ≥1.26 x ULN or if AST >10 x ULN
Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicity
Monitor patients closely
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产地国家: 美国
原产地英文商品名:
ABRAXANE VIAL LYOPH POWDER SDV 2mg/ml 100mg/50ml/vial.
原产地英文药品名:
PACLITAXEL PROTEIN-BOUND
中文参考商品译名:
ABRAXANE 2毫克/毫升 100毫克/50毫升/瓶
中文参考药品译名:
紫杉醇白蛋白结合
生产厂家英文名:
Celgene
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