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近日，美国食品药品监督管理局（FDA）批准了二氯化镭Ra 223（Xofigo注射剂，拜耳医药保健制药公司）用于治疗去势抵抗性前列腺癌，并伴有骨转移症状和未知原因内脏转移性疾病的病人（详见Xofigo药品说明）。Xofigo是一种发射α粒子的放疗药物，能够模拟钙的作用，并与羟基磷灰石形成复合物以加快骨更新，例如促进骨转移.
FDA的药物评价和研究中心血液学和肿瘤产品室主任Richard Pazdur，M.D.说：“Xofigo与骨中矿物质结合直接释放辐射至骨肿瘤，限制对周围正常组织的损伤，”“Xofigo是在去年被FDA批准的显示有延长转移前列腺癌男性生命的第二个前列腺癌药物”。
批准日期：2013年5月23日 公司：拜耳医药
Xofigo(二氯化镭233[radium Ra 223 dichloride])注射剂，为静脉使用
美国初次批准：2013
作用机制
Xofigo的活性部位是α 粒子发射同位素镭-223(为二氯化镭223)，模拟钙和在骨更新增加区与骨矿物质羟基磷灰石形成复合物，例如骨转移(见表2)。α发射体的高线性能量转移(80 keV/微米)导致在临近细胞中双链DNA的高频断裂，导致对骨转移的抗肿瘤作用。来自二氯化镭-223的α粒子范围小于100微米(小于10个细胞直径)限制对周围正常组织损伤。
适应证和用途
Xofigo是一种α粒子发射放射性治疗药物适用为有去势耐受前列腺癌，症状性骨转移和无已知内脏转移病患者的治疗。
剂量和给药方法
Xofigo的给药方案是50kBq (1.35微居里)每kg体重，给予 4周间隔共6次注射。
剂型和规格
单次使用小瓶浓度1,000 kBq/mL(27微居里/mL)在参比日期有总放射性6,000 kBq/小瓶(162微居里/小瓶)在参比日期。
Xofigo® (radium Ra 223 dichloride) injection is indicated for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases and no known visceral metastatic disease.
Important Safety Information
•Contraindications: Xofigo is contraindicated in women who are or may become pregnant. Xofigo can cause fetal harm when administered to a pregnant woman
•Bone Marrow Suppression: In the randomized trial, 2% of patients in the Xofigo arm experienced bone marrow failure or ongoing pancytopenia, compared to no patients treated with placebo. There were two deaths due to bone marrow failure. For 7 of 13 patients treated with Xofigo bone marrow failure was ongoing at the time of death. Among the 13 patients who experienced bone marrow failure, 54% required blood transfusions. Four percent (4%) of patients in the Xofigo arm and 2% in the placebo arm permanently discontinued therapy due to bone marrow suppression. In the randomized trial, deaths related to vascular hemorrhage in association with myelosuppression were observed in 1% of Xofigo-treated patients compared to 0.3% of patients treated with placebo. The incidence of infection-related deaths (2%), serious infections (10%), and febrile neutropenia (<1%) was similar for patients treated with Xofigo and placebo. Myelosuppression—notably thrombocytopenia, neutropenia, pancytopenia, and leukopenia—has been reported in patients treated with Xofigo.
Monitor patients with evidence of compromised bone marrow reserve closely and provide supportive care measures when clinically indicated. Discontinue Xofigo in patients who experience life-threatening complications despite supportive care for bone marrow failure
•Hematological Evaluation: Monitor blood counts at baseline and prior to every dose of Xofigo. Prior to first administering Xofigo, the absolute neutrophil count (ANC) should be ≥1.5 x 109/L, the platelet count ≥100 x 109/L, and hemoglobin ≥10 g/dL. Prior to subsequent administrations, the ANC should be ≥1 x 109/L and the platelet count
≥50 x 109/L. Discontinue Xofigo if hematologic values do not recover within 6 to 8 weeks after the last administration despite receiving supportive care
•Concomitant Use with Chemotherapy: Safety and efficacy of concomitant chemotherapy with Xofigo have not been established. Outside of a clinical trial, concomitant use of Xofigo in patients on chemotherapy is not recommended due to the potential for additive myelosuppression. If chemotherapy, other systemic radioisotopes, or hemibody external radiotherapy are administered during the treatment period, Xofigo should be discontinued
•Administration and Radiation Protection: Xofigo should be received, used, and administered only by authorized persons in designated clinical settings. The administration of Xofigo is associated with potential risks to other persons from radiation or contamination from spills of bodily fluids such as urine, feces, or vomit. Therefore, radiation protection precautions must be taken in accordance with national and local regulations
•Adverse Reactions: The most common adverse reactions (≥10%) in patients receiving Xofigo were nausea, diarrhea, vomiting, and peripheral edema. Grade 3 and 4 adverse events were reported in 57% of Xofigo-treated patients and 63% of placebo-treated patients. The most common hematologic laboratory abnormalities in Xofigo-treated patients (≥10%) were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia
XOFIGO Rx
Pharmacological Class:
Alpha particle-emitting radioactive therapeutic agent.
Active Ingredient(s):
Radium Ra 223 dichloride 1000 kBq/mL (27 microcurie/mL) with a total radioactivity of 6000 kBq/vial (162 microcurie/vial) at the reference date; IV injection.
Company
Bayer Healthcare Pharmaceuticals Inc.
Indication(s):
Treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease.
Pharmacology:
Xofigo mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases.
Clinical Trials:
The efficacy and safety of Xofigo were evaluated in a double-blind, randomized, placebo-controlled Phase 3 clinical trial of patients with castration-resistant prostate cancer with symptomatic bone metastases. The primary efficacy endpoint was overall survival. A key secondary efficacy endpoint was time to first symptomatic skeletal event (SSE) defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention. All patients were to continue androgen deprivation therapy. At the cut-off date of the preplanned interim analysis, a total of 809 patients had been randomized 2:1 to receive Xofigo 50kBq (1.35 microcurie)/kg intravenously every 4 weeks for 6 cycles (n = 541) plus best standard of care or matching placebo plus best standard of care (n = 268). Best standard of care included local EBRT, corticosteroids, antiandrogens, estrogens, estramustine or ketoconazole. Therapy was continued until unacceptable toxicity or initiation of cytotoxic chemotherapy, other systemic radioisotope, hemibody EBRT or other investigational drug.
The prespecified interim analysis of overall survival revealed a statistically significant improvement in patients receiving Xofigo (14 months; 95% CI [12.1, 15.8]) plus best standard of care compared with patients receiving placebo (11.2 months; 95% CI [9.0, 13.2]); (P = 0.00185, HR = 0.695 [0.552, 0.875]) plus best standard of care. An exploratory updated overall survival analysis performed before patient crossover with an additional 214 events resulted in findings consistent with the interim analysis. The survival results were supported by a delay in the time to first SSE favoring the Xofigo arm. The majority of events consisted of EBRT to bone metastases.
Legal Classification:
Rx
Adults:
See full labeling. Administer by slow IV over 1 min. 50kBq (1.35 microcurie) per kg given at 4 week intervals for 6 injections.
Children:
<18 years: not established.
Contraindication(s):
Women who are or may become pregnant. Pregnancy (Category X).
Warnings/Precautions:
Not for use in women. Bone marrow suppression. Perform hematologic evaluation at baseline and prior to every dose. Before 1st dose, the ANC should be ≥1.5 X 109/L, platelets ≥100 X 109/L and hemoglobin ≥10g/dL. Before subsequent doses, the ANC should be ≥1 X 109/L and platelets ≥50 X 109/L; discontinue if no recovery within 6–8 weeks after last dose despite receiving supportive care. Monitor closely if evidence of compromised bone marrow reserve. Discontinue if life-threatening complications occur despite supportive care for bone marrow failure. Monitor oral intake and fluid status carefully. Males (use condoms) and female partners of reproductive potential should use highly effective contraceptive method during and 6 months after completion. Nursing mothers: not recommended.
Interaction(s)
Concomitant chemotherapy: not established. Discontinue if concomitant with chemotherapy, other systemic radioisotopes or hemibody external radiotherapy.
Adverse Reaction(s)
Nausea, diarrhea, vomiting, peripheral edema, anemia, lymphocytopenia, leukopenia, thrombocytopenia, neutropenia.
How Supplied:
Single-use vials (6mL)—1
LAST UPDATED:
9/5/2013 |
