Home » Drug Information » FDA Approved Drugs » 2004
Medical Areas: Gastroenterology | Oncology | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved February 2004
Treatment Area: Colorectal Cancer
Avastin is an anti-VEGF monoclonal antibody for the treatment of
Avastin, used in combination with intravenous
5-fluorouracil-based chemotherapy, is indicated for first-line
treatment of patients with metastatic carcinoma of the colon or
The recommended dose of Avastin is 5 mg/kg given once every 14
days as an IV infusion until disease progression is detected.
FDA approval of Avastin for colorectal cancer was based on two
(STUDY 1 / STUDY 2) randomized, controlled trials in combination
with intravenous 5-fluorouracil-based chemotherapy.
Study 1 was a double-blind trial enrolling 813 subjects with
metastatic carcinoma of the colon or rectum. Subjects were
randomized to bolus-IFL (irinotecan 125 mg/m2 IV, 5-fluorouracil
500 mg/m2 IV, and leucovorin 20 mg/m2 IV given once weekly for 4
weeks every 6 weeks) plus placebo (Arm 1), bolus-IFL plus Avastin
(5 mg/kg every 2 weeks) (Arm 2) or 5-FU/LV plus Avastin (5 mg/kg
every 2 weeks) (Arm 3). Among the subjects, 57% had an ECOG
performance status of 0. The primary endpoint of this trial was
overall survival. Results showed that the overall survival in Arms
1 & 2 was 20.3 months with Avastin compared with 15.6 months
with placebo. The median progression-free survival was 10.6 months
with Avastin compared with 6.4 months with placebo. Data showed
that the median overall survival in Arm 3 was 18.3 months, median
progression-free survival was 8.8 months, overall response rate was
39%, and median duration of response was 8.5 months.
Study 2 tested Avastin in combination with 5-FU/LV and enrolled
as first-line treatment of metastatic colorectal cancer. Subjects
were randomized to receive 5-FU/LV (5-fluorouracil 500 mg/m2,
leucovorin 500 mg/m2 weekly for 6 weeks every 8 weeks) or 5-FU/LV
plus Avastin (5 mg/kg every 2 weeks) or 5-FU/LV plus Avastin (10
mg/kg every 2 weeks). The primary endpoints of the trial were
objective response rate and progression-free survival. Results
showed that progression-free survival was significantly better in
subjects receiving 5-FU/LV plus Avastin at 5 mg/kg when compared to
those not receiving Avastin. However, overall survival and overall
response rate were not significantly different. Results for
subjects receiving 5-FU/LV plus Avastin at 10 mg/kg were not
significantly different than without Avastin.
Adverse events associated with the use of Avastin may include
(but are not limited to) the following:
- Abdominal Pain
- Deep Vein Thrombosis
- Intra-Abdominal Thrombosis
Mechanism of Action
Bevacizumab binds VEGF and prevents the interaction of VEGF to
its receptors (Flt-1 and KDR) on the surface of endothelial cells.
The interaction of VEGF with its receptors leads to endothelial
cell proliferation and new blood vessel formation in in vitro
models of angiogenesis.
In preclinical studies, administration of bevacizumab to
xenotransplant models of colon cancer in nude mice caused reduction
of microvascular growth and inhibition of metastatic disease
progression. In January 2000, preclinical results showed that
bevacizumab was more effective at preventing growth of tumor cell
lines in animal models when it was combined with sub-threshold
doses of cisplatin or trastuzumab.
Folprecht G, Kohne CH.The role of new agents in
the treatment of colorectal cancer. Oncology.
Presta LG, Chen H, O'Connor SJ, Chisholm V, Meng YG,
Krummen L, et al. Humanization of an anti-vascular
endothelial growth factor monoclonal antibody for the therapy of
solid tumors and other disorders. Cancer Res
Salgaller ML Technology evaluation:
bevacizumab, Genentech/Roche. Curr Opin Mol Ther. 2003
For additional information regarding Avastin or colorectal
cancer, please contact The Avastin Web Site