【药品名】： 帕尼单抗 Panitumumab

【药品类型】：处方药,其它科用药,抗肿瘤药
【药品性能】：适用于结直肠癌
【药品说明】：帕尼单抗治疗结肠直肠癌具独特优势帕尼单抗(Panitumumab)是第一个靶向表皮生长因子受体(EGFR)的全人源化单克隆抗体，而表皮生长因子受体则是一种在肿瘤细胞信号传导过程中扮演着重要角色的蛋白。帕尼单抗即将成为表皮生长因子受体抑制剂中的又一新成员，后者开发的第一适应证为经过标准化疗治疗失败的转移性结肠直肠癌。----------------------------------------------
帕尼单抗治疗结肠直肠癌具独特优势帕尼单抗(Panitumumab)是第一个靶向表皮生长因子受体(EGFR)的全人源化单克隆抗体，而表皮生长因子受体则是一种在肿瘤细胞信号传导过程中扮演着重要角色的蛋白。帕尼单抗即将成为表皮生长因子受体抑制剂中的又一新成员，后者开发的第一适应证为经过标准化疗治疗失败的转移性结肠直肠癌。
结肠直肠癌是美国第三常见类型肿瘤。美国癌症学会估计，美国2005年新诊出的结肠癌和直肠癌患者数分别达到10.5万人和4.23万人。
Ⅲ期临床试验显现，Amgen有限公司的这一在研药物能够改善经多种化疗方案治疗失败之转移性结肠直肠癌患者的疾病无进展存活时间和响应率。帕尼单抗的上述用途已于2005年7月获得了FDA授予的\"快通道\"地位。Amgen有限公司及其合作开发伙伴Abgenix公司目前正在准备提请FDA批准帕尼单抗用于那些已经进行标准化疗，或者包含奥沙利铂（Oxaliplatin）和伊利替坎（Irinotecan）的方案治疗失败之后转移性结肠直肠癌患者治疗的生物制剂许可申请材料，预期2006年第一季度内可以完成并随即提交FDA。
目前，帕尼单抗也在进行单用或合用其他抗肿瘤药物治疗各类型肿瘤，包括结肠直肠癌、肺癌和肾癌等的多项临床试验。另外，帕尼单抗亦在进行合用化疗药物和Genentech有限公司的结肠直肠癌治疗药物倍伐单抗（Bevacizumab，Avastin）治疗早期阶段结肠直肠癌患者的临床研究。
帕尼单抗属免疫球蛋白IgG2型单克隆抗体，它能以高度亲和性与表皮生长因子受体结合。帕尼单抗是应用Abgenix公司的XenoMouse技术生产的，这种技术能用来制造一种不含鼠源性蛋白的全人源化单克隆抗体。由于机体的免疫系统可自嵌合型抗体中识别出鼠蛋白，因此会由此引发免疫响应并以输注反应和变态反应等形式表现出来。开发不含鼠蛋白的全人源化单克隆抗体的目的就在于，保留嵌合型抗体疗效的基础上使这类免疫响应潜力降至最低程度。
表皮生长因子受体虽能帮助调控机体许多不同类型资本的正常生长，但它也会刺激肿瘤细胞的生长。实际上，许多类型的肿瘤细胞存活都需经由表皮生长因子受体介导的信号传导。表皮生长因子受体位于肿瘤细胞表面，它可因机体中天然发生蛋白如表皮生长因子和α-转化生长因子等与之结合而被激活。后者首先表现为受体形状变化，而后即会触发刺激肿瘤细胞生长的内在细胞信号传导过程。帕尼单抗能够结合至表皮生长因子受体，由此通过阻止表皮生长因子和α-转化生长因子等天然配基与之结合而干扰可致刺激肿瘤细胞生长并使这些细胞存活的信号传导过程。
Amgen有限公司宣称，因更少不良反应和更为便利的剂量方案，帕尼单抗具有优于类似药物西妥单抗（Cetuximab，Er鄄bitux）的潜力。业内人士认为，基于倍伐单抗和西妥单抗在不应性结肠直肠癌患者中显现出的协同活性，若Ⅲ期临床试验能够证实帕尼单抗加至氟尿嘧啶-亚叶酸-奥沙利铂和倍伐单抗方案中一线治疗结肠直肠癌有益，那么帕尼单抗就能凭借这更为便利的剂量方案（每两周1次对西妥单抗的每周1次用药）而将成为临床标准一线疗法。
研究还进一步揭示，帕尼单抗较西妥单抗的具有更多特性，包括更长的半衰期、更高的受体亲和性和更好的免疫耐受性等。帕尼单抗的药动学性质也提示，其用药不必要像西妥单抗那样，必须首先给予负荷剂量。帕尼单抗和西妥单抗分属全人源化和嵌合型鼠-人抗体，故帕尼单抗的耐受性亦应优于西妥单抗。
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　　Indication

　　Vectibix® (panitumumab) is indicated as a single agent for the treatment of epidermal growth factor receptor (EGFR) -expressing, metastatic colorectal carcinoma (mCRC) with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens.

　　The effectiveness of Vectibix® as a single agent for the treatment of EGFR-expressing mCRC is based on progression-free survival. Currently, no data demonstrate an improvement in disease-related symptoms or increased survival with Vectibix®.

　　Retrospective subset analyses of metastatic colorectal cancer trials have not shown a treatment benefit for Vectibix® in patients whose tumors had KRAS mutations in codon 12 or 13. Use of Vectibix® is not recommended for the treatment of colorectal cancer with these mutations.

　　IMPORTANT SAFETY INFORMATION

　　WARNING: DERMATOLOGIC TOXICITY and INFUSION REACTIONS

　　Dermatologic Toxicity: Dermatologic toxicities occurred in 89% of patients and were severe (NCI-CTC grade 3 or higher) in 12% of patients receiving Vectibix® monotherapy. [See Dosage and Administration (2.1), Warnings and Precautions (5.1), and Adverse Reactions (6.1)].

　　Infusion Reactions: Severe infusion reactions occurred in approximately 1% of patients. Fatal infusion reactions occurred in postmarketing experience.

　　[See Dosage and Administration (2.1), Warnings and Precautions (5.2), and Adverse Reactions (6.1, 6.3)].

　　In Study 1, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 16% of patients with mCRC receiving Vectibix®.

　　Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, necrotizing fasciitis and abscesses requiring incisions and drainage were reported. Withhold or discontinue Vectibix® for severe or life-threatening dermatologic toxicity and monitor for inflammatory or infectious sequelae.

　　Terminate the infusion for severe infusion reactions.

　　Vectibix® is not indicated for use in combination with chemotherapy. In an interim analysis of a randomized clinical trial, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased overall survival and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions.

　　NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in patients treated with Vectibix® included rash/dermatitis/acneiform (26% vs 1%); diarrhea (23% vs 12%); dehydration (16% vs 5%), primarily occurring in patients with diarrhea; hypokalemia (10% vs 4%); stomatitis/mucositis (4% vs < 1%); and hypomagnesemia (4% vs 0%). NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in patients treated with Vectibix® (7% vs 4%) and included fatal events in 3 (< 1%) patients treated with Vectibix®.

　　In a single-arm study of 19 patients receiving Vectibix® in combination with IFL, the incidence of NCI-CTC grade 3-4 diarrhea was 58%; in addition, grade 5 diarrhea occurred in 1 patient. In a single-arm study of 24 patients receiving Vectibix® plus FOLFIRI, the incidence of NCI-CTC grade 3 diarrhea was 25%.

　　Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix®. Patients with a history or evidence of interstitial pneumonitis, pulmonary fibrosis, were excluded from most clinical trials. Therefore, the estimated risk in a general population that includes such patients is uncertain. Cases of interstitial lung disease (ILD), including fatalities, have been reported in patients treated with Vectibix®. Interrupt Vectibix® therapy for the acute onset or worsening of pulmonary symptoms. Discontinue Vectibix® therapy if ILD is confirmed.

　　In a randomized, controlled clinical trial, median magnesium levels decreased by 0.1 mmol/L in the Vectibix® arm; hypomagnesemia (NCI-CTC grade 3 or 4) requiring oral or IV electrolyte repletion occurred in 2% of patients. Hypomagnesemia occurred 6 weeks or longer after the initiation of Vectibix®. In some patients, both hypomagnesemia and hypocalcemia occurred. Patients' electrolytes should be periodically monitored during and for 8 weeks after the completion of Vectibix® therapy. Institute appropriate treatment (eg, oral or intravenous electrolyte repletion) as needed.

　　Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats, and limit sun exposure while receiving Vectibix® and for 2 months after the last dose.

　　Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix®. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix® for acute or worsening keratitis.

　　Adequate contraception in both males and females must be used while receiving Vectibix® and for 6 months after the last dose of Vectibix® therapy. Vectibix® may be transmitted from the mother to the developing fetus and has the potential to cause fetal harm when administered to pregnant women.

　　Discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother. If nursing is interrupted, it should not be resumed earlier than 2 months following the last dose of Vectibix®.

　　The most common adverse events of Vectibix® are skin rash with variable presentations, hypomagnesemia, paronychia, fatigue, abdominal pain, nausea, and diarrhea, including diarrhea resulting in dehydration.

　　The most serious adverse events of Vectibix® are pulmonary fibrosis, pulmonary embolism, severe dermatologic toxicity complicated by infectious sequelae and septic death, infusion reactions, abdominal pain, hypomagnesemia, nausea, vomiting, and constipation.