英文药名: Vectibix(Panitumumab Injection)

中文药名: 维克替比(帕尼单抗注射剂)

生产厂家: Amgen Inc

药品介绍；
 
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。

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。

部份中文VECTIBIX帕尼单抗处方（仅供参考）

vectibix®（帕尼单抗）注射液静脉滴注

最初美国批准：2006年
 
适应症
vectibix是一种表皮生长因子受体拮抗剂作为一个单一的病情恶化后，氟尿嘧啶，奥沙利铂，伊立替康化疗转移性大肠癌的治疗代理表示。批准是基于无进展生存期，没有数据表明，在改善疾病相关症状或增加存活率与Vectibix。
转移性结直肠癌的临床试验的回顾性亚组分析没有显示为Vectibix在12或13位密码子有KRAS突变的肿瘤患者的治疗效益。不推荐使用的Vectibix这些突变与大肠癌的治疗。

剂量和用法
管理在6毫克/公斤，每14天超过60分钟静脉滴注（≤1000毫克）或90分钟（> 1000毫克）。
输液反应：输液速度减少50％为轻度反应，终止输注严重的输液反应。根据反应的严重程度和/或持久，永久停止Vectibix。
皮肤毒性：全心全意为严重或无法忍受的毒性;可能恢复50％的剂量，如果毒性改进。
 
剂型和优势

单次使用的小瓶（20毫克/毫升）：100毫克/ 5毫升，200 mg/10毫升，400 mg/20毫升
 
禁忌
没有。
 
注意事项：
皮肤毒性：扣留或停止Vectibix和炎症或感染后遗症患者患有严重皮肤病毒性监测。限制暴露于太阳。
输液反应：终止输注严重的输液反应。
联合化疗的毒性增加：Vectibix未标明与化疗结合使用。
肺纤维化/间质性肺疾病（ILD）：永久停止Vectibix开发ILD患者。
期间和Vectibix治疗，并采取相应的治疗结束后8周电解液耗尽/监测：监测电解质。
眼部毒性：监视器角膜炎或溃疡性角膜炎的证据。中断或终止Vectibix急性或恶化性角膜炎
 
不良反应
最常见的不良反应（≥20％）是皮肤的毒性（即红斑，痤疮样皮炎，皮肤瘙痒，剥脱，皮疹，裂缝），甲沟炎，低镁血症，乏力，腹痛，恶心，腹泻和便秘。

在特殊人群中使用

妊娠：根据动物数据，可能会对胎儿造成伤害。
Amgen的妊娠监测计划怀孕的患者。
哺乳母亲停止哺乳或停止药物，考虑到母亲的药物的重要性。

修改日期：12/2011

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
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.

ベクティビックス点滴静注100mg／ベクティビックス点滴静注400mg

有効成分に関する理化学的知見

薬効分類名

抗悪性腫瘍剤／ヒト型抗EGFR注1）モノクローナル抗体
注1）EGFR ： Epidermal growth factor receptor（上皮細胞増殖因子受容体）

商標名
Vectibix

一般名
パニツムマブ（遺伝子組換え）
（Panitumumab（Genetical Recombination））〔JAN〕

本質
ヒト抗ヒトEGFRモノクローナル抗体であるIgG2をコードするゲノムDNAを導入したチャイニーズハムスター卵巣細胞で産生される214個のアミノ酸残基（C1028H1588N274O336S6，分子量：23,353.63）からなる軽鎖2分子及び445個のアミノ酸残基（C2171H3355N573O672S18，分子量：48,811.47）からなる重鎖2分子から構成される糖タンパク質（分子量：約147,000）であり，重鎖サブユニットの主成分はC末端のリジンを欠く。

承認条件

国内での治験症例が極めて限られていることから、製造販売後、一定数の症例に係るデータが集積されるまでの間は、全症例を対象に使用成績調査を実施することにより、本剤使用患者の背景情報を把握するとともに、本剤の安全性及び有効性に関するデータを早期に収集し、本剤の適正使用に必要な措置を講じること。

包装

点滴静注100mg：1バイアル

点滴静注400mg：1バイアル

製造販売元
武田薬品工業株式会社

附件；www.info.pmda.go.jp/go/pack/4291417A1020_1_04/