FDA批准新生物技术药Kepivance（商品名；通用名：palifermin）以治疗与癌症治疗有关的粘膜炎
12月15日，FDA批准一种新的静脉注射型生物制品Kepivance，旨在减少某些进行化疗和放疗以备接受骨髓移植的血癌患者发生粘膜炎的几率。Palifermin的使用也可以缩短该疾病的病程。
粘膜炎（口腔内侧粘膜的剧烈疼痛和溃疡），是与骨髓移植相关的高剂量化疗和放疗所引起的一种常见并发症。患有粘膜炎的患者进食和吞咽困难。该症状最严重时，患者根本无法饮食，而必须通过静脉接受营养和流质替代物。
Palifermin是自然存在被称作角质化细胞生长因子（keratinocyte growth factor，KGF）的人体蛋白的一种人造版本。KGF刺激皮肤中的细胞以及口腔、胃和结肠表层细胞的生长。Palifermin与天然的KGF一样，也能够刺激口腔表层细胞的生长。这被认为导致了在癌症治疗时被杀死的这些细胞的更快替换，并被认为加速了口腔溃疡愈合的进程。
一项由212位正在接受与骨髓移植有关的高剂量化疗和放疗的白血病或淋巴瘤患者参与的临床研究表明，未接受palifermin治疗的患者中有98％发生严重粘膜炎，而接受palifermin治疗的患者中只有63％发生严重粘膜炎。此外，接受palifermin治疗的患者中严重粘膜炎的病程平均为3天，而安慰剂组的病程平均为9天。
Palifermin的使用方法是：在癌症治疗开始前的三天以及治疗后的三天内通过静脉给药。
Palifermin最常见的副作用为皮疹、口腔内异样感（比如麻刺感）以及血液蛋白含量升高（指示胰脏激惹[pancreatic irritation]）。迄今还未报告与palifermin的使用相关的严重副作用。在因白血病或淋巴瘤之外的癌症而被治疗的患者中，Palifermin还未被证明是安全和有效的。

Palifermin由位于美国加利福尼亚州Thousand Oaks的阿目金公司（Amgen Inc.）生产，以商品名Kepivance进行上市销售。

Amgen公司2004年12月15日宣布FDA已批准了Kepivance(palifermin)用于治疗严重口腔溃疡，而这种口腔溃疡可能会发生在服用过高剂量化疗又接受了骨髓移植的血癌病患者身上。该药用于非血癌患者上的有效性和安全性还正在进行中。
在双盲临床试验中，血癌患者在接受高剂量化疗加放射治疗前，被随机静注60mμg·kg-1· d-1(n=106)或安慰剂（n=106），共3d。接着患者接受骨髓移植，并被再给予3d的kepivance或安慰剂。最严重的口腔溃疡（4级）发生率在kepivanc组（20%）比安慰机组中（62%）降低了3倍，3~4级溃疡发生率也减少大约1/3（63%比98%）。Kepivanc缩短溃疡疼痛时间（2~4级）达1周之多（8d比安慰机组的14d）。研究发现被kepivanc治疗的患者显著减少了口腔和喉头红肿，吃，喝、吞咽和说话能力都有显著改善。此外，接受kepivanc的患者要求吗啡止痛的时间也比安慰机组少（7d比11d）。
kepivanc是一种重组人体角质化细胞生长因子，它通过保护口腔和喉部表皮细胞免遭化疗和放疗的损害而减少溃疡的发生，并可刺激新的表皮细胞在溃疡伤面的生长和发肩。Kepivanc的安全性的耐受性较好。不良反应为皮疹、瘙痒、皮肤红肿、皮肤异常感、口/舌感紊乱，但均为轻微或中度，且短暂。

【原产地英文商品名】KEPIVANCE 6.25mg/vial 6vials/box
【原产地英文药品名】PALIFERMIN
【中文参考商品译名】凯望斯 6.25毫克/瓶 6瓶/盒
【中文参考药品译名】帕利夫明
【生产厂家中文参考译名】安进
【生产厂家英文名】Amgen

What is Kepivance?
Kepivance is a powder that is made up into a solution for injection. It contains the active substance palifermin.

What is Kepivance used for?
Kepivance is used to decrease the frequency, duration and severity of oral mucositis (inflammation of the lining of the mouth, ranging from soreness and redness to severe ulceration). Kepivance is used in adults who are likely to develop severe mucositis because they have blood cancer, and are being treated with myeloablative chemotherapy (medicines to destroy the bone marrow) in combination with radiotherapy (treatment with radiation) and an autologous haematopoietic stem-cell transplant (a transplant of their own blood-producing cells).

The medicine can only be obtained with a prescription.

How is Kepivance used?
The use of Kepivance should be supervised by a doctor who has experience in anticancer therapy.

It is given as an injection into a vein for a total of six doses. Three doses are given on three consecutive days before myeloablative therapy, finishing 24 to 48 hours before the therapy. The remaining three doses are given on three consecutive days after myeloablative therapy, with the first dose given on the day of the stem-cell transplant. There should be a gap of more than four days between the two three-day courses of Kepivance.

How does Kepivance work?
The active substance in Kepivance, palifermin, is a growth factor that stimulates the ‘epithelial’ cells that line the mouth and gastrointestinal tract to grow and develop. Palifermin is very similar to a natural growth factor found in the body called keratinocyte growth factor (KGF).

Epithelial cells in the mouth are normally replaced by the body every few days. In patients receiving chemotherapy and radiotherapy, the cells are not replaced as quickly, which leads to the development of mucositis. Kepivance stimulates the growth of the epithelial cells, helping to reduce the incidence, severity and duration of oral mucositis in cancer patients undergoing intensive therapy.

Palifermin is produced by a method known as ‘recombinant DNA technology’: it is made by a bacterium that has received a gene (DNA), which makes it able to produce palifermin. The replacement palifermin acts in the same way as naturally produced KGF.

How has Kepivance been studied?
Kepivance has been compared with placebo (a dummy treatment) in one main study in 212 adults receiving chemotherapy and radiotherapy for a blood cancer (mostly non-Hodgkin’s lymphoma). The main measure of effectiveness was the number of days during which patients experienced severe oral mucositis.

At the request of the CHMP, the company carried out a further study comparing two schedules of Kepivance with placebo. The study involved 281 adults who were receiving chemotherapy to treat multiple myeloma (a type of blood cancer), but without any radiotherapy.

What benefit has Kepivance shown during the studies?
In the main study, the patients receiving chemotherapy and radiotherapy had severe oral mucositis for a shorter time if they received Kepivance (3.7 days, on average) than if they received placebo (10.4 days, on average). Patients receiving Kepivance also reported less mouth and throat soreness with improved swallowing, drinking, eating and talking. However, in the study of patients receiving chemotherapy without radiation, there was no difference in the severity of mucositis between the patients receiving placebo and those receiving either schedule of Kepivance.

What is the risk associated with Kepivance?
The most common side effects with Kepivance (seen in more than 1 patient in 10) are dysgeusia (taste disturbances), increased levels of lipase and amylase (enzymes used in digestion), hypertrophy (increase in the number or size of cells) or discoloration of the mouth and tongue, rash, pruritus (itching), erythema (redness), arthralgia (joint pain), oedema (swelling), pain and pyrexia (fever). For the full list of all side effects reported with Kepivance, see the package leaflet.

Kepivance should not be used in people who may be hypersensitive (allergic) to palifermin, proteins produced by Escherichia coli (a bacterium) or any of the other ingredients.

Why has Kepivance been approved?
The CHMP decided that Kepivance’s benefits are greater than its risks and recommended that it be given marketing authorisation.

Other information about Kepivance
The European Commission granted a marketing authorisation valid throughout the European Union for Kepivance on 25 October 2005. The marketing authorisation holder is Biovitrum AB (publ). The marketing authorisation is valid for an unlimited period.

For more information about treatment with Kepivance, read the package leaflet (also part of the EPAR).