本品为PEG化的L-门冬酰胺酶制剂。某些白血病细胞依赖于天门冬酰胺氨基酸存活，而L-门冬酰胺酶能够减少此种氨基酸。美国FDA于1994年2月批准本品用于治疗急性成淋巴细胞性白血病，在需要接受L-门冬酰胺酶治疗而又对天然L-门冬酰胺酶过敏的患者中使用。不但降低了免疫原性，而且用药更易为患者所接受——只需二周1次用药，而非重组的L-门冬酰胺酶需要一周2次用药。 Oncaspar is indicated for patients with acute lymphoblastic leukemia who require L-asparaginase in their treatment regimen, but have developed hypersensitivity to the native forms of L-asparaginase (SEE CLINICAL PHARMACOLOGY). ONCASPAR, like native L-asparaginase, is generally used in combination with other chemotherapeutic agents, such as vincristine, methotrexate, cytarabine, daunorubicin, and doxorubicin. 1,5 Use of ONCASPAR as a single agent should only be undertaken when multi-agent chemotherapy is judged to be inappropriate for the patient. 【英文名】  Pegaspargase（Oncaspar） 【结构式】  本品是L-天门冬酰胺酶的修型（来自大肠杆菌）是由单甲氧基聚乙烯乙二醇（PEG）的共价结合单位产生的酶，分子量约5000。 【作用特点】  某些肿瘤细胞本身不能合成L-天门冬酰胺（它是合成蛋白质必需的氨基酸）。本品可使进入肿瘤L-天门冬酰胺水解，肿瘤细胞得不到L-天门冬酰胺，而影响其蛋白质的合成，最终使肿瘤细胞的增长繁殖受到抑制。正常组织细胞自身有合成L-天门冬酰胺的能力，不受本品的影响。本品的抗原性比天然L-天门冬酰胺酶低。血浆半衰期比天然型显著延长。 【功能主治】  本品适用于急性淋巴细胞白血病（ALL），这种病人治疗中需要L-天门冬酰胺酶，若已对天然L-天门冬酰胺酶产生过敏，可试用本品。一般本品与其它化疗药物并用，如长春新碱、甲氨喋吟，阿糖胞苷，柔红霉素和阿霉素。只有在确认多种化疗药物不适用时才可单用本品。本品的疗效已证实与天然L-天门冬酰胺酶类似。对天然L-天门冬酰胺酶十分严重过敏反应的病人，也能耐受本品。本品也已在非何杰金淋巴瘤和急性骨髓性白血病被评价。然而目前还不是指定的适应症。 【用法用量】  本品可肌内注射或静脉滴注。以肌内注射的过敏性或其它不良反应发生率较低。本品每14日1次，2500IU／m2。儿童体表面积小于0.6m2，剂量按每14日82.5IU／kg。本品的作用持续时间长，比用天然L-天门冬酰胺酶的剂量小，给药次数少。本品肌注，单次给药容量应限于2ml，如果＞2ml，应使用多处部位注射。静脉给药时，本品应以100ml生理盐水或5％葡萄糖液稀释后连续滴注l～2／小时。 【注意事项】  病人用药后必须严密观察1小时并做好过敏反应的急救准备。有胰腺炎病史的患者禁用本品。并应经常检查血清淀粉酶，以早期发现胰腺炎。有明显出血史的病人禁用本品。如果可能，应当避免使用可能增加出血危险的药物如华法令、肝素、潘生丁、阿斯匹林、非甾体抗炎药等。对肝功能不良或同时接受其它有强烈肝毒性药物的患者慎用本品。本品作用迅速，并观察到某些病人出现肿瘤溶解综合征。本品可能是接触性刺激剂，溶液必须小心处理，并带手套，必须避免吸入蒸气和接触皮肤、粘膜，尤其眼睛。如果接触，应用大量水冲洗至少15分钟。本品使用时不可振摇。 【制剂规格】 注射剂：每小瓶5ml：3750IU。 【贮藏】 本品须冷藏，但不可冻结。因为冻结可破坏本品的活性，若已发生冻结应废弃。 【原产地英文商品名】ONCASPAR-750IU/mL,5mL/Vial 【原产地英文药品名】PEGASPARGASE 【原产地英文化合物名称】PEGASPARGASE 【中文参考商品译名】昂卡司帕-750IU/毫升，5毫升/瓶 【中文参考药品译名】培门冬酶 【中文参考化合物名称】聚乙烯苷醇轭合物 【生产厂家中文参考译名】恩仲制药 【生产厂家英文名:Enzon ONCASPAR (pegaspargase) injection, solution [Sigma-Tau Pharmaceuticals, Inc.] HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Oncaspar® safely and effectively. See full prescribing information for Oncaspar®. Oncaspar®(pegaspargase) injection, for intramuscular or intravenous use Initial U.S. Approval: 1994   INDICATIONS AND USAGE Oncaspar® is an asparagine specific enzyme indicated as a component of a multi-agent chemotherapeutic regimen for treatment of patients with: First line acute lymphoblastic leukemia (1.1) Acute lymphoblastic leukemia and hypersensitivity to asparaginase (1.2)   DOSAGE AND ADMINISTRATION 2,500 International Units/m2 intramuscularly or intravenously no more frequently than every 14 days. (2.1) For intramuscular administration, limit the volume at a single injection site to 2 mL; if greater than 2 mL, use multiple injection sites. (2.2) For intravenous administration, give over a period of 1 to 2 hours in 100 mL of sodium chloride or dextrose injection 5%, through an infusion that is already running. (2.2) Do not administer Oncaspar® if drug has been frozen, stored at room temperature for more than 48 hours, or shaken or vigorously agitated. (2.3)   DOSAGE FORMS AND STRENGTHS 3,750 International Units/5 mL solution in a single-use vial. (3)   CONTRAINDICATIONS History of serious allergic reactions to Oncaspar®. (4) History of serious thrombosis with prior L-asparaginase therapy. (4) History of pancreatitis with prior L-asparaginase therapy. (4) History of serious hemorrhagic events with prior L-asparaginase therapy. (4) WARNINGS AND PRECAUTIONS If the following occur - discontinue Oncaspar®: Anaphylaxis or serious allergic reactions (5.1) Thrombosis (5.2) Pancreatitis (5.3) Glucose intolerance, in some cases irreversible, can occur. (5.4) Coagulopathy can occur. Perform appropriate monitoring. (5.5)   ADVERSE REACTIONS Most common adverse reactions (≥2%) are allergic reactions (including anaphylaxis), central nervous system (CNS) thrombosis, coagulopathy, elevated transaminases, hyperbilirubinemia, hyperglycemia, and pancreatitis. (6) See 17 for PATIENT COUNSELING INFORMATION  Revised: 05/2011 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 First Line Acute Lymphoblastic Leukemia (ALL) Oncaspar® is indicated as a component of a multi-agent chemotherapeutic regimen for the first line treatment of patients with ALL. 1.2 Acute Lymphoblastic Leukemia and Hypersensitivity to Asparaginase Oncaspar® is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with ALL and hypersensitivity to native forms of L-asparaginase. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dose The recommended dose of Oncaspar® is 2,500 International Units/m2 intramuscularly or intravenously. Oncaspar® should be administered no more frequently than every 14 days. 2.2 Instructions for Administration When Oncaspar® is administered intramuscularly, the volume at a single injection site should be limited to 2 mL. If the volume to be administered is greater than 2 mL, multiple injection sites should be used. Oncaspar® does not contain a preservative. Use only one dose per vial; discard unused product. When administered intravenously, Oncaspar® should be given over a period of 1 to 2 hours in 100 mL of sodium chloride or dextrose injection 5%, through an infusion that is already running. After the solution is diluted for intravenous use, the solution should be used immediately. If immediate use is not possible, the diluted solution should be stored refrigerated at 2°C to 8°C (36°F to 46°F). Storage after dilution should not exceed 48 hours from the time of preparation to completion of administration. Protect infusion bags from direct sunlight. 2.3 Preparation and Handling Precautions Do not administer Oncaspar® if drug has been: frozen stored at room temperature 15°-25°C (59°-77°F) for more than 48 hours shaken or vigorously agitated [see How Supplied/Storage and Handling (16)] Parenteral drug products should be inspected visually for particulate matter, cloudiness, or discoloration prior to administration, whenever solution and container permit. If any of these are present, discard the vial. 3 DOSAGE FORMS AND STRENGTHS 3,750 International Units/5 mL solution in a single-use vial. 4 CONTRAINDICATIONS History of serious allergic reactions to Oncaspar®. History of serious thrombosis with prior L-asparaginase therapy. History of pancreatitis with prior L-asparaginase therapy. History of serious hemorrhagic events with prior L-asparaginase therapy. 5 WARNINGS AND PRECAUTIONS 5.1 Anaphylaxis and Serious Allergic Reactions Serious allergic reactions can occur in patients receiving Oncaspar®. The risk of serious allergic reactions is higher in patients with known hypersensitivity to other forms of L-asparaginase. Observe patients for 1 hour after administration of Oncaspar® in a setting with resuscitation equipment and other agents necessary to treat anaphylaxis (for example, epinephrine, oxygen, intravenous steroids, antihistamines). Discontinue Oncaspar® in patients with serious allergic reactions. 5.2 Thrombosis Serious thrombotic events, including sagittal sinus thrombosis can occur in patients receiving Oncaspar®. Discontinue Oncaspar® in patients with serious thrombotic events. 5.3 Pancreatitis Pancreatitis can occur in patients receiving Oncaspar®. Evaluate patients with abdominal pain for evidence of pancreatitis. Discontinue Oncaspar® in patients with pancreatitis. 5.4 Glucose Intolerance Glucose intolerance can occur in patients receiving Oncaspar®. In some cases, glucose intolerance is irreversible. 5.5 Coagulopathy Increased prothrombin time, increased partial thromboplastin time, and hypofibrinogenemia can occur in patients receiving Oncaspar®. Monitor coagulation parameters at baseline and periodically during and after treatment. Initiate treatment with fresh-frozen plasma to replace coagulation factors in patients with severe or symptomatic coagulopathy. 6 ADVERSE REACTIONS The following serious adverse reactions occur with Oncaspar® treatment [see Warnings and Precautions (5)]: Anaphylaxis and serious allergic reactions Serious thrombosis Pancreatitis Glucose intolerance Coagulopathy The most common adverse reactions with Oncaspar® are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in clinical practice. First-Line ALL The data presented below are derived from 2 studies in patients with standard-risk ALL who received Oncaspar® as a component of first-line multi-agent chemotherapy. Study 1 was a randomized (1:1), active-controlled study that enrolled 118 patients, with a median age of 4.7 years (1.1-9.9 years), of whom 54% were males and 65% White, 14% Hispanic, 8% Black, 8% Asian, and 6% other. Of the 59 patients in Study 1 who were randomized to Oncaspar®, 48 patients (81%) received all 3 planned doses of Oncaspar®, 6 (10%) received 2 doses, 4 (7%) received 1 dose, and 1 patient (2%) did not receive the assigned treatment. Study 2 is an ongoing, multi-factorial design study in which all patients received Oncaspar® as a component of various multi-agent chemotherapy regimens; interim safety data are available for 2,770 patients. Study participants had a median age of 4 years (1-10 years), and were 55% male, 68% White, 18% Hispanic, 4% Black, 3% Asian, and 7% other. Per protocol, the schedule of Oncaspar® varied by treatment arm, with intermittent doses of Oncaspar® for up to 10 months. In Study 1, detailed safety information was collected for pre-specified adverse reactions identified as asparaginase-induced adverse reactions and for grade 3 and 4 non-hematologic adverse reactions according to the Children’s Cancer Group (CCG) Toxicity and Complication Criteria. The per-patient incidence, by treatment arm, for these selected adverse reactions occurring at a severity of grade 3 or 4 are presented in Table 1 below: TABLE 1 STUDY 1: PER-PATIENT INCIDENCE OF SELECTED GRADE 3 AND 4 ADVERSE REACTIONS Aspartate aminotransferase, alanine aminotransferase. Prolonged prothrombin time or partial thromboplastin time; or hypofibrinogenemia. Oncaspar® (n=58) Native E. coli L-Asparaginase (n=59) Abnormal Liver Tests 3 (5%) 5 (8%)     Elevated Transaminases* 2 (3%) 4 (7%)     Hyperbilirubinemia 1 (2%) 1 (2%) Hyperglycemia 3 (5%) 2 (3%) Central Nervous System Thrombosis 2 (3%) 2 (3%) Coagulopathy† 1 (2%) 3 (5%) Pancreatitis 1 (2%) 1 (2%) Clinical Allergic Reactions to Asparaginase 1 (2%) 0 Safety data were collected in Study 2 only for National Cancer Institute Common Toxicity Criteria (NCI CTC) version 2.0, grade 3 and 4 non-hematologic toxicities. In this study, the per-patient incidence for the following adverse reactions occurring during treatment courses in which patients received Oncaspar® were: elevated transaminases, 11%; coagulopathy, 7%; hyperglycemia, 5%; CNS thrombosis/hemorrhage, 2%; pancreatitis, 2%; clinical allergic reaction, 1%; and hyperbilirubinemia, 1%. There were 3 deaths due to pancreatitis. Previously Treated ALL Adverse reaction information was obtained from 5 clinical trials that enrolled a total of 174 patients with relapsed ALL who received Oncaspar® as a single agent or in combination with multi-agent chemotherapy. The toxicity profile of Oncaspar® in patients with previously treated relapsed ALL is similar to that reported above with the exception of clinical allergic reactions (see Table 2). The most common adverse reactions of Oncaspar® were clinical allergic reactions, elevated transaminases, hyperbilirubinemia, and coagulopathies. The most common serious adverse events due to Oncaspar® treatment were thrombosis (4%), hyperglycemia requiring insulin therapy (3%), and pancreatitis (1%). 6.2 Clinical Allergic Reactions Clinical allergic reactions include the following: bronchospasm, hypotension, laryngeal edema, local erythema or swelling, systemic rash, and urticaria. First-Line ALL Among 58 Oncaspar®-treated patients enrolled in Study 1, clinical allergic reactions were reported in 2 patients (3%). One patient experienced a grade 1 allergic reaction and the other grade 3 hives; both occurred during the first delayed intensification phase of the study (see Table 2). Previously Treated ALL Among 62 patients with relapsed ALL and prior hypersensitivity reactions to asparaginase, 35 patients (56%) had a history of clinical allergic reactions to native Escherichia (E.) coli L-asparaginase, and 27 patients (44%) had a history of clinical allergic reactions to both native E. coli and native Erwinia L-asparaginase. Twenty (32%) of these 62 patients experienced clinical allergic reactions to Oncaspar® (see Table 2). Among 112 patients with relapsed ALL with no prior hypersensitivity reactions to asparaginase, 11 patients (10%) experienced clinical allergic reactions to Oncaspar® (see Table 2). TABLE 2 INCIDENCE OF CLINICAL ALLERGIC REACTIONS, OVERALL AND BY SEVERITY GRADE Toxicity Grade, n (%) Patient Status 1 2 3 4 Total Previously Hypersensitive Patients (n=62) 7 (11) 8 (13) 4 (6) 1 (2) 20 (32) Non- Hypersensitive Patients (n=112) 5 (4) 4 (4) 1 (1) 1 (1) 11 (10) First Line (n=58) 1 (2) 0 1 (2) 0 2 (3) 6.3 Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity, defined as development of binding and/or neutralizing antibodies to the product. In Study 1, Oncaspar®-treated patients were assessed for evidence of binding antibodies using an enzyme-linked immunosorbent assay (ELISA) method. The incidence of protocol-specified “high-titer” antibody formation was 2% in Induction (n=48), 10% in Delayed Intensification 1 (n=50), and 11% in Delayed Intensification 2 (n=44). There is insufficient information to determine whether the development of antibodies is associated with an increased risk of clinical allergic reactions, altered pharmacokinetics, or loss of anti-leukemic efficacy. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody positivity in an assay may be influenced by several factors including sample handling, concomitant medications, and underlying disease. Therefore, comparison of the incidence of antibodies to Oncaspar® with the incidence of antibodies to other products may be misleading. 7 DRUG INTERACTIONS No formal drug interaction studies, between Oncaspar® and other drugs, have been performed. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Oncaspar®. It is also not known whether Oncaspar® can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Oncaspar® should be given to a pregnant woman only if clearly needed. 8.3 Nursing Mothers It is not known whether Oncaspar® 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 from Oncaspar®, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use [see Clinical Studies (14.1)] 8.5 Geriatric Use Clinical studies of Oncaspar® did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently than younger subjects. 10 OVERDOSAGE Three patients received 10,000 International Units/m2 of Oncaspar® as an intravenous infusion. One patient experienced a slight increase in liver enzymes. A second patient developed a rash 10 minutes after the start of the infusion, which was controlled with the administration of an antihistamine and by slowing down the infusion rate. A third patient did not experience any adverse reactions. 11 DESCRIPTION Oncaspar® (pegaspargase) is L-asparaginase (L-asparagine amidohydrolase) that is covalently conjugated to monomethoxypolyethylene glycol (mPEG). L-asparaginase is a tetrameric enzyme that is produced endogenously by E. coli and consists of identical 34.5 kDa subunits. Approximately 69 to 82 molecules of mPEG are linked to L-asparaginase; the molecular weight of each mPEG molecule is about 5 kDa. Oncaspar® activity is expressed in International Units. One International Unit of L-asparaginase is defined as the amount of enzyme required to generate 1 micromole of ammonia per minute at pH 7.3 and 37°C. Oncaspar® is supplied as a clear, colorless, preservative-free, isotonic sterile solution in phosphate-buffered saline, pH 7.3. Each milliliter contains 750 ± 150 International Units of pegaspargase, dibasic sodium phosphate, USP (5.58 mg), monobasic sodium phosphate, USP, (1.20 mg) and sodium chloride, USP (8.50 mg) in water for injection, USP. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of Oncaspar® is thought to be based on selective killing of leukemic cells due to depletion of plasma asparagine. Some leukemic cells are unable to synthesize asparagine due to a lack of asparagine synthetase and are dependent on an exogenous source of asparagine for survival. Depletion of asparagine, which results from treatment with the enzyme L-asparaginase, kills the leukemic cells. Normal cells, however, are less affected by the depletion due to their ability to synthesize asparagine. 12.2 Pharmacodynamics In Study 1, pharmacodynamics were assessed in 57 newly diagnosed pediatric patients with standard-risk ALL who received three intramuscular doses of Oncaspar® (2,500 International Units/m2), one each during induction and two delayed intensification treatment phases. Pharmacodynamic activity was assessed through serial measurements of asparagine in sera (n=57) and cerebrospinal fluid (CSF) (n=50). The data for asparagine depletion are presented in CLINICAL STUDIES [see Clinical Studies (14)]. 12.3 Pharmacokinetics Pharmacokinetic assessments were based on an enzymatic assay measuring asparaginase activity. Serum pharmacokinetics were assessed in 34 newly diagnosed pediatric patients with standard-risk ALL in Study 1 following intramuscular administration of 2,500 International Units/m2. The elimination half-life of Oncaspar® was approximately 5.8 days during the induction phase. Similar elimination half-lives were observed during Delayed Intensification 1 and Delayed Intensification 2. Concentrations greater than 0.1 International Units/mL were observed in over 90% of the samples from patients treated with Oncaspar® during induction, Delayed Intensification 1, and Delayed Intensification 2 for approximately 20 days. In 3 pharmacokinetic studies, 37 patients with relapsed ALL received Oncaspar® at 2,500 International Units/m2 intramuscularly every 2 weeks. The plasma half-life of Oncaspar® was 3.2 ± 1.8 days in 9 patients who were previously hypersensitive to native E. coli L-asparaginase and 5.7 ± 3.2 days in 28 non-hypersensitive patients. The area under the plasma concentration-time curve (AUC) was 9.5 ± 4.0 International Units/mL/day in the previously hypersensitive patients and 9.8 ± 6.0 International Units/mL/day in the non-hypersensitive patients. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No long-term carcinogenicity studies in animals have been performed with Oncaspar®. No relevant studies addressing mutagenic potential have been conducted. Oncaspar® did not exhibit a mutagenic effect when tested against Salmonella typhimurium strains in the Ames assay. No studies have been performed on impairment of fertility. 14 CLINICAL STUDIES 14.1 First-Line ALL The safety and effectiveness of Oncaspar® was evaluated in an open-label, multicenter, randomized, active-controlled study (Study 1). In this study, 118 pediatric patients aged 1 to 9 years with previously untreated standard-risk ALL were randomized 1:1 to Oncaspar® or native E. coli L-asparaginase as part of combination therapy. Oncaspar® was administered intramuscularly at a dose of 2,500 International Units/m2 on Day 3 of the 4-week induction phase and on Day 3 of each of two 8-week delayed intensification phases. Native E. coli L-asparaginase was administered intramuscularly at a dose of 6,000 International Units/m2 three times weekly for 9 doses during induction and for 6 doses during each delayed intensification phase. The primary determination of effectiveness was based on demonstration of similar asparagine depletion (magnitude and duration) in the Oncaspar® and native E. coli L-asparaginase arms. The protocol-specified goal was achievement of asparagine depletion to a serum concentration of ≤1 μM. The proportion of patients with this level of depletion was similar between the 2 study arms during all 3 phases of treatment at the protocol-specified time points. In all phases of treatment, serum asparagine concentrations decreased within 4 days of the first dose of asparaginase in the treatment phase and remained low for approximately 3 weeks for both Oncaspar® and native E. coli L-asparaginase arms. Serum asparagine concentrations during the induction phase are shown in Figure 1. The patterns of serum asparagine depletion in the 2 delayed intensification phases are similar to the pattern of serum asparagine depletion in the induction phase. FIGURE 1 MEAN (± STANDARD ERROR) SERUM ASPARAGINE CONCENTRATIONS DURING STUDY 1 INDUCTION PHASE Note:   Oncaspar® (2,500 International Units/m2 intramuscular) was administered on Day 3 of the 4-week induction phase.              Native E. coli L-asparaginase (6,000 International Units/m2 intramuscular) was administered 3 times weekly for 9              doses during induction. CSF asparagine concentrations were determined in 50 patients during the induction phase. CSF asparagine decreased from a mean pretreatment concentration of 3.1 µM to 1.7 µM on Day 4 ± 1 and 1.5 µM at 25 ± 1 days after administration of Oncaspar®. These findings were similar to those observed in the native E. coli L-asparaginase treatment arm. While the 3-year Event-Free Survival (EFS) for the Oncaspar® and native E. coli L-asparaginase study arms were similar and in the range of 80%, Study 1 was not designed to evaluate for differences in EFS rates. 14.2 ALL Patients Hypersensitive to Asparaginase The safety and effectiveness of Oncaspar® was evaluated in 4 open-label studies enrolling a total of 42 patients with multiply-relapsed, acute leukemia [39 (93%) with ALL] with a history of prior clinical allergic reaction to asparaginase. Hypersensitivity to asparaginase was defined by a history of systemic rash, urticaria, bronchospasm, laryngeal edema, hypotension, or local erythema, urticaria, or swelling, greater than 2 centimeters, for at least 10 minutes following administration of any form of native E. coli L-asparaginase. All patients received Oncaspar® at a dose of 2,000 or 2,500 International Units/m2 administered intramuscularly or intravenously every 14 days. Patients received Oncaspar® as a single agent or in combination with multi-agent chemotherapy. The re-induction response rate was 50% (95% confidence interval: 35%, 65%), based upon 36% complete remissions and 14% partial remissions. These results were similar to the overall response rates reported for patients with ALL receiving second-line, native E. coli L-asparaginase-containing re-induction chemotherapy. Anti-tumor activity was also observed with single-agent Oncaspar®. Three responses (1 complete remission and 2 partial remissions) were observed in 9 adult and pediatric patients with relapsed ALL and hypersensitivity to native E. coli L-asparaginase. 16 HOW SUPPLIED/STORAGE AND HANDLING Oncaspar® (pegaspargase) is supplied as a sterile solution in Type I single-use vials containing 3,750 International Units of L-asparaginase per 5 mL solution (NDC 54482-301-01). Store Oncaspar® under refrigeration at 2°C to 8°C (36°F to 46°F). Do not shake or freeze product. Protect from light. Do not use Oncaspar® after the expiration date on the vial. 17 PATIENT COUNSELING INFORMATION 17.1 Serious Allergic Reactions Patients should be informed of the possibility of serious allergic reactions, including anaphylaxis, and to immediately report any swellings or difficulty breathing. 17.2 Thrombosis Patients should be advised to immediately report any severe headache. Arm or leg swelling, acute shortness of breath, and chest pain also should be reported immediately. 17.3 Pancreatitis Patients should be advised to immediately report any severe abdominal pain. 17.4 Glucose Intolerance Patients should be advised to report excessive thirst or any increase in the volume or frequency of urination. U.S. License No. 1850 I-301-21-US-A 美国FDA批准Oncaspar用于新诊断的急性淋巴细胞白血病   美国FDA今天扩大了Oncaspar的批准用途，将包括治疗患有新诊断的急性淋巴细胞白血病(acute lymphoblastic leukemia，简写ALL)的儿童和成人，作为多药化疗方案的一部分。先前FDA在1994年批准Oncaspar只能用于不能接受抗癌药L-saparaginase(L-天门冬酰胺酶)的患有ALL的患者，因为他们对L-天门冬酰胺酶过敏。 Oncaspar是FDA首次批准的将附有新格式处方药信息的产品之一，新格式旨在给医疗专业人员提供清楚简明的信息。 “今天的宣布进一步证明了FDA对改善癌症患者的生命质量的承诺。该治疗药是目前疗法的一个有价值的替代物，”FDA的CDER主任Steven Galson博士称。 白血病是一种白细胞的癌症，急性白血病患者体内有不能帮助身体抗击感染的无效白细胞。据估计，2006年美国将诊断出25000例新白血病病例。在这些新白血病病例中，大约6500例将成为ALL型白血病，其中大约2500例将发生于儿童，4000例发生于成人。 用Oncaspar代替目前使用的药品L-天门冬酰胺酶，显著减少了所需的药物注射数量，在长达20周的疗程期间，标准治疗需要注射Elspar(L-天门冬酰胺酶)21次，而Oncaspar只需注射3次。 这次批准是以儿童癌症组织(Children’s Cancer Group)对118名儿科患者进行的一个随机多中心试验为基础的，儿童癌症组织是一个由美国国家癌症研究所资助的合作性肿瘤组织。在该试验中，研究者证明了Oncaspar可以安全有效地替代Elspar作为多药物癌症治疗方案的一部分。 Oncaspar的严重副作用包括过敏反应(过敏休克)，其它严重过敏反应，血栓，中风，胰腺炎，葡萄糖不耐受和出血等问题。