2015年11月23日，美国食品和药物监管局（FDA）批准了Nivolumab（商品名Opdivo，美国施贵宝公司生产），用于治疗晚期肾细胞癌。这些患者先前接受过抗 血管生成药物治疗，但病情仍有恶化。Nivolumab是一种结合于PD-1受体的单克隆抗体，通过阻断PD-1和PD-L1及PD-L2间的相互作用， 从而阻断 PD-1通路介导的免疫抑制反应，包括抗肿瘤免疫反应。
该批准是基于一项随机临床试验的有效结果。晚期肾细胞癌患者被随机分配到Nivolumab组或依维莫司（Everolimus）组。试验结果显 示，Nivolumab优于依维莫司。Nivolumab组的平均总生存期为25个月，而依维莫司组的则为19.6个月。Nivolumab组的有效率为 21.5%，而依维莫司组的则为3.9%。Nivolumab组的平均有效期为23个月，而依维莫司组的则为13.7个月。
Nivolumab最常见的副作用（发生率大于或等于20％）为虚弱、咳嗽、恶心、皮疹、呼吸困难、腹泻、便秘、食欲下降、背和关节疼痛。最常见的化验异常（发生率大于或等于30％）为肌酐升高、淋巴细胞减少、贫血、肝功能异常、低钠、甘油三酯增高和高钾。47%的患者发生严重副作用，最常见的严重副作用 （发生率大于或等于2％）包括急性肾功能损伤、胸腔积液、肺炎、腹泻和高血钙。免疫介导的副作用包括肺炎、肠炎、肝炎、肾炎、内分泌病和脑炎。
Nivolumab的推荐剂量为3毫克/每公斤体重，60分钟静脉点滴，每两周一次。
Opdivo (Nivolumab Injection)
OPDIVO Rx
OPDIVO
Bladder, kidney, and other urologic cancers
Melanoma and other skin cancers
Respiratory and thoracic cancers Only 4 drugs may be compared at once
Generic Name and Formulations:
Nivolumab 10mg/mL; per vial; soln for IV infusion after dilution; preservative-free; contains mannitol.
Company:
Bristol-Myers Squibb
Select therapeutic use: Bladder, kidney, and other urologic cancers
Melanoma and other skin cancers
Respiratory and thoracic cancers
Indications for OPDIVO:
Advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy.
Adult:
Give as IV infusion over 60mins. 3mg/kg every 2 weeks until disease progression or unacceptable toxicity. Dose modifications: see full labeling.
Children:
Not established.
Warnings/Precautions:
See full labeling. Monitor for any immune-mediated adverse reactions; permanently discontinue or withhold, and give corticosteroids (at 1–2mg/kg/day prednisone equivalents) based on severity of event. Permanently discontinue for any life-threatening or Grade 4 adverse reaction, Grade 3 or 4 pneumonitis, Grade 3 (with ipilimumab) or 4 colitis, AST/ALT >5XULN or total bilirubin >3XULN, SCr >6XULN, Grade 4 hypophysitis, Grade 3 or 4 adrenal insufficiency, Grade 4 hyperglycemia, Grade 4 rash, immune-mediated encephalitis, recurring Grade 3 or 4 adverse reaction, requirement for ≥10mg/day prednisone (or equivalent) for >12 weeks, or persistent Grade 2 or 3 adverse reactions lasting ≥12 weeks. Grade 2 pneumonitis, Grade 2 or 3 (as single agent) colitis, AST/ALT >3–5XULN or total bilirubin >1.5–3XULN, SCr >1.5–6XULN, new onset moderate-to-severe neurologic symptoms, any other Grade 2 or 3 adverse reactions; withhold dose, give corticosteroids, and when resolved, consider re-initiation. Discontinue if severe or life-threatening infusion reactions occur. Monitor for abnormal liver tests, elevated serum creatinine, hyperglycemia, and thyroid function prior to and during treatment; give replacement therapy for hypothyroidism. Moderate or severe hepatic impairment: not studied. Pregnancy: avoid. Use effective contraception during therapy and for ≥5 months after final dose. Nursing mothers: not recommended.
Pharmacological Class:
Human programmed death receptor-1 (PD-1)-blocking antibody.
Adverse Reactions:
Asthenic conditions, cough, nausea, rash, dyspnea, diarrhea, constipation, decreased appetite, back pain, arthralgia; immune-mediated reactions (may be fatal).
Generic Availability:
NO
How Supplied:
Single-use vial (4mL, 10mL)—1
Opdivo (ni |
