阿瓦斯丁，英文名Avastin，是治療直腸癌的新藥。
基本介紹
- 藥品名稱：瓦斯丁
- 外文名：Avastin
- 主要適用症：治療直腸癌
治療直腸癌的新藥Avastin
人類基因知識突飛猛進，令開發癌症藥物的研究有大突破。三種由生物技術發展出來的抗癌新藥，專門對付體內某種助長癌瘤生長擴散的物質，它們在消滅癌細胞的同時，並不損害健康細胞，因此比普通的化療高出一籌。其中最矚目的是治療直腸癌的新藥Avastin ，它能阻止癌瘤自製血管，使其無法吸收養分「餓死」。臨床測試證明，它將可用來治療晚期病人，令其生存率大增50 ％，平均壽命延長5 個月。研究結果本月初在美國臨床腫瘤學會年會上公布時，與會者都振奮地交頭接耳，因為他們知道這些研究成果的劃時代意義。
明報報導，在1970 年代，哈佛大學研究員福爾曼首次指出，癌症腫瘤似乎能夠在人體內自製新血管，供其吸取氧氣和養分之用，毒瘤藉此不斷擴散，由一個器官擴散至另一個器官，最終奪命。他因此推斷，廢去腫瘤製造血管的能力，使其「餓死」，便能減慢甚或停止腫瘤擴散。
平均延長壽命5 個月
一直以來，科學家的研究皆不甚成功，直至最近，科學家終於以其理論製成新藥Avastin ，並首次以大規模臨床測試證實福爾曼的假設。Avastin 是一種蛋白質，也是一種人造抗體，專門對付被某些癌瘤用來誘使血管形成的物質。
令化療效果更快更持久
Avastin 的臨? 測試有800 人參與，在標準化療之外再服用Avastin 的結腸直腸癌（Colorectal cancer ）病人，證實比那些只接受化療的病人，在研究期間的生存機會高出一半。
要指出某療法是否有效的指標繁多而複雜，不過一項令人易於理解的計算方法是有否令病人壽命延長，而Avastin 被發現令平均壽命由15.6 個月延長到20.3 個月。《紐約時報》說，若一種新抗癌藥能延長病人壽命兩三個月便等於成功，Avastin 延命5 個月，已超出期望。
參與臨床試驗的加州大學舊金山分校胃腸腫瘤專家韋洛克說：你看到的是病人彷佛馬上受惠，在感覺上以及腫瘤負荷上都減輕了。我想它真的使化療效果加快，而且可能令效果更持久。
研究人員說，副作用基本上可以控制，只是會令許多病人血壓上升，這可用普通方法治療。Avastin 已顯示對乳癌效果不佳，但該公司正研究它對胰臟癌、前列腺癌、卵巢癌和腎癌的效用。 可望明年推出市場
目前，多家生物技術公司共同研發出近10 種類似藥理的藥物，Avastin 被視為樣板，備受業界關注。由於臨? 測試結果理據充足，研發出Avastin 的美國著名基因工程公司Genentech 可能會在明年內向美國食品及藥物管理局申請推出市場，而不像慣例那樣再作第二次大型研究。
另外兩種藥物，包括紐約生物科技製藥公司ImClone 研發的治療結腸直腸癌藥Erbitux ，以及AstraZeneca 公司的肺癌藥Iressa ，都是用以阻擋一種體內分子，使其無法協助癌腫瘤發展起對化療的抵抗能力。臨? 實驗都證實，它們能令瀕死病人的癌瘤縮小，只是尚未能如Avastin 那樣延長病人壽命。
癌症醫生絕少說「治癒」，因為癌症隨時都會復發，但現在很多醫生都希望，若把這兩三種目前世界上最先進的抗癌藥物結合現有的化療方法，或能長久抑制腫瘤。因此醫學界都歡呼，他們即將踏入治癌新紀元。專家相信，以深厚基因知識為基礎的療法，已開始有效對付各大癌症殺手，例如肺癌、乳癌、直腸癌和前列腺癌等。
醫學界：標誌治癌新紀元
對癌病的臨床研究已有15 年的加州大學腫瘤專家韋洛克說：我向來對所謂研究進展有保留，但也不得不說這是劃時代的。它令研究者、病人和生物醫藥公司而言都是一大鼓舞，真是令人興奮得不得了。
AVASTIN(Bevacizumab)英文說明書
U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
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1.14.1.3 Labeling Text 1
AVASTIN™ 2
(Bevacizumab) 3
For Intravenous Use 4
WARNINGS 5
Gastrointestinal Perforations/Wound Healing Complications 6
AVASTIN administration can result in the development of gastrointestinal 7
perforation and wound dehiscence, in some instances resulting in fatality. 8
Gastrointestinal perforation, sometimes associated with intra-abdominal 9
abscess, occurred throughout treatment with AVASTIN (i.e., was not 10
correlated to duration of exposure). The incidence of gastrointestinal 11
perforation in patients receiving bolus-IFL with AVASTIN was 2%. The 12
typical presentation was reported as abdominal pain associated with 13
symptoms such as constipation and vomiting. Gastrointestinal perforation 14
should be included in the differential diagnosis of patients presenting with 15
abdominal pain on AVASTIN. AVASTIN therapy should be permanently 16
discontinued in patients with gastrointestinal perforation or wound 17
dehiscence requiring medical intervention. The appropriate interval 18
between termination of AVASTIN and subsequent elective surgery 19
required to avoid the risks of impaired wound healing/wound dehiscence 20
has not been determined. (See WARNINGS: Gastrointestinal 21
Perforations/Wound Healing Complications and DOSAGE AND 22
ADMINISTRATION: Dose Modifications.) 23
Hemorrhage 24
Serious, and in some cases fatal, hemoptysis has occurred in patients with 25
non–small cell lung cancer treated with chemotherapy and AVASTIN. In 26
a small study, the incidence of serious or fatal hemoptysis was 31% in 27
patients with squamous histology and 4% in patients with adenocarcinoma 28
receiving AVASTIN as compared to no cases in patients treated with 29
chemotherapy alone. Patients with recent hemoptysis should not receive 30
AVASTIN. (See WARNINGS: Hemorrhage and DOSAGE AND 31
ADMINISTRATION: Dose Modifications .) 32
U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
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DESCRIPTION 33
AVASTINä (Bevacizumab) is a recombinant humanized monoclonal 34
IgG1 antibody that binds to and inhibits the biologic activity of human 35
vascular endothelial growth factor (VEGF) in in vitro and in vivo assay 36
systems. Bevacizumab contains human framework regions and the 37
complementarity-determining regions of a murine antibody that binds to 38
VEGF (1). Bevacizumab is produced in a Chinese Hamster Ovary 39
mammalian cell expression system in a nutrient medium containing the 40
antibiotic gentamicin and has a molecular weight of approximately 41
149 kilodaltons. AVASTIN is a clear to slightly opalescent, colorless to 42
pale brown, sterile, pH 6.2 solution for intravenous (IV) infusion. 43
AVASTIN is supplied in 100 mg and 400 mg preservative- free, single- use 44
vials to deliver 4 mL or 16 mL of AVASTIN (25 mg/mL). The 100 mg 45
product is formulated in 240 mg a,a-trehalose dihydrate, 23.2 mg sodium 46
phosphate (monobasic, monohydrate), 4.8 mg sodium phosphate (dibasic, 47
anhydrous), 1.6 mg polysorbate 20, and Water for Injection, USP. The 48
400 mg product is formulated in 960 mg a,a-trehalose dihydrate, 92.8 mg 49
sodium phosphate (monobasic, monohydrate), 19.2 mg sodium phosphate 50
(dibasic, anhydrous), 6.4 mg polysorbate 20, and Water for Injection, 51
USP. 52
CLINICAL PHARMACOLOGY 53
Mechanism of Action 54
Bevacizumab binds VEGF and prevents the interaction of VEGF to its 55
receptors (Flt-1 and KDR) on the surface of endothelial cells. The 56
interaction of VEGF with its receptors leads to endothelial cell 57
proliferation and new blood vessel formation in in vitro models of 58
angiogenesis. Administration of Bevacizumab to xenotransplant models 59
of colon cancer in nude (athymic) mice caused reduction of microvascular 60
growth and inhibition of metastatic disease progression. 61
Pharmacokinetics 62
The pharmacokinetic profile of Bevacizumab was assessed using an assay 63
that measures total serum Bevacizumab concentrations (i.e., the assay did 64
U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
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not distinguish between free Bevacizumab and Bevacizumab bound to 65
VEGF ligand). Based on a population pharmacokinetic analysis of 66
491 patients who received 1 to 20 mg/kg of AVASTIN weekly, every 67
2 weeks, or every 3 weeks, the estimated half-life of Bevacizumab was 68
approximately 20 days (range 11-50 days). The predicted time to reach 69
steady state was 100 days. The accumulation ratio following a dose of 70
10 mg/kg of Bevacizumab every 2 weeks was 2.8. 71
The clearance of Bevacizumab varied by body weight, by gender, and by 72
tumor burden. After correcting for body weight, males had a higher 73
Bevacizumab clearance (0.262 L/day vs. 0.207 L/day) and a larger Vc 74
(3.25 L vs. 2.66 L) than females. Patients with higher tumor burden (at or 75
above median value of tumor surface area) had a higher Bevacizumab 76
clearance (0.249 L/day vs. 0.199 L/day) than patients with tumor burdens 77
below the median. In a randomized study of 813 patients (Study 1), there 78
was no evidence of lesser efficacy (hazard ratio for overall survival) in 79
males or patients with higher tumor burden treated with AVASTIN as 80
compared to females and patients with low tumor burden. The 81
relationship between Bevacizumab exposure and clinical outcomes has not 82
been explored. 83
Special Populations 84
Analyses of demographic data suggest that no dose adjustments are 85
necessary for age or sex. 86
Patients with renal impairment. No studies have been conducted to 87
examine the pharmacokinetics of Bevacizumab in patients with renal 88
impairment. 89
Patients with hepatic dysfunction. No studies have been conducted to 90
examine the pharmacokinetics of Bevacizumab in patients with hepatic 91
impairment. 92
U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
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CLINICAL STUDIES 93
The safety and efficacy of AVASTIN in the initial treatment of patients 94
with metastatic carcinoma of the colon and rectum were studied in two 95
randomized, controlled clinical trials in combination with intravenous 96
5-fluorouracil–based chemotherapy. 97
AVASTIN in Combination with Bolus-IFL 98
Study 1 was a randomized, double-blind, active-controlled clinical trial 99
evaluating AVASTIN as first- line treatment of metastatic carcinoma of the 100
colon or rectum. Patients were randomized to bolus-IFL (irinotecan 101
125 mg/m2 IV, 5-fluorouracil 500 mg/m2 IV, and leucovorin 20 mg/m2 IV 102
given once weekly for 4 weeks every 6 weeks) plus placebo (Arm 1), 103
bolus-IFL plus AVASTIN (5 mg/kg every 2 weeks) (Arm 2), or 5-FU/LV 104
plus AVASTIN (5 mg/kg every 2 weeks) (Arm 3). Enrollment in Arm 3 105
was discontinued, as pre-specified, when the toxicity of AVASTIN in 106
combination with the bolus-IFL regimen was deemed acceptable. 107
Of the 813 patients randomized to Arms 1 and 2, the median age was 60, 108
40% were female, and 79% were Caucasian. Fifty-seven percent had an 109
ECOG performance status of 0. Twenty-one percent had a rectal primary 110
and 28% received prior adjuvant chemotherapy. In the majority of 111
patients, 56%, the dominant site of disease was extra-abdominal, while the 112
liver was the dominant site in 38% of patients. The patient characteristics 113
were similar across the study arms. The primary endpoint of this trial was 114
overall survival. Results are presented in Table 1 and Figure 1. 115
U.S. BLA Amendment: Bevacizumab—Genentech, Inc.
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Table 1
Study 1 Efficacy Results
IFL + Placebo
IFL + AVASTIN
5 mg/kg q 2 wks
Number of Patients 411 402
Overall Survivala
Median (months) 15.6 20.3
Hazard ratio 0.66
Progression-Free Survivala
Median (months) 6.4 10.6
Hazard ratio 0.54
Overall Response Rateb
Rate (percent) 35% 45%
Duration of Response
Median (months) 7.1 10.4
......
Avastin獲準作為晚期結腸癌二線治療藥 (2006-6-22)
生物製藥公司Genentech在6月20日稱，FDA已批准Avastin的擴大適應症，即作為晚期結腸癌的二線治療藥物。
此前，Avastin+化療聯用已獲準作為晚期結腸癌的一線治療藥。
FONT color=#733c29>vastin的擴大適應症，即作為晚期結腸癌的二線治療藥物。
此前，Avastin+化療聯用已獲準作為晚期結腸癌的一線治療藥。
