Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer

Abstract

The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.

Low-dose metronomic cyclophosphamide treatment mediates ischemia-dependent K-ras mutation in colorectal carcinoma xenografts

“…These observations, together with the results of clinical trials using antiangiogenic agents (Yang et al, 2003;Hurwitz et al, 2004;Miller et al, 2005a, b;Motzer and Bukowski, 2006;Varker et al, 2007) suggest a more complex impact of this treatment modality than previously anticipated. In most current clinical studies, antiangiogenic agents are used as adjuvant therapy in combination with chemotherapy or sometimes chemoradiotherapy.…”

“…Currently, intervention with antiangiogenic agents is performed in relatively late stages of disease, where there are more angiogenic and survival pathways involved and manipulations of any single factor (such as inhibition of vascular endothelial growth factor) likely become less critical for cancer progression Kerbel and Folkman, 2002;Franco et al, 2006). Interestingly, addition of bevacizumab to first-line chemotherapy in patients with metastatic colorectal cancer increased response rates and prolonged overall survival (Hurwitz et al, 2004). Nevertheless, the response to these drugs varied significantly among patients, and in all studies performed to date numerous patients underwent an antiangiogenic regimen without apparent significant benefit in survival or time to progression (Yang et al, 2003;Miller et al, 2005a, b;Motzer and Bukowski, 2006;Varker et al, 2007).…”

“…This linkage paved the way to clinical trials with antiangiogenic agents, which in some cases have dramatically changed the standards of care (Miller et al, 2005a, b;Motzer and Bukowski, 2006;Varker et al, 2007). In particular, bevacuzimab/avastin, a humanized monoclonal-neutralizing antibody directed against vascular endothelial growth factor has since 2004 become incorporated into the first-line therapies in metastatic colorectal carcinoma (CRC) (Hurwitz et al, 2004) and other malignancies (Gasparini et al, 2005). In addition to such targeted antiangiogenic agents designed to obliterate a well-defined molecular mechanism (for example, vascular endothelial growth factor/vascular endothelial growth factor receptor pathway), blood vessel inhibitory properties have also been uncovered in drugs with ostensibly unrelated activities, including cytotoxic anticancer chemotherapeutics (Browder et al, 2000;Klement et al, 2000).…”

The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo

“…In addition, VEGF-A regulates the function and physiology of some cancer cells themselves, by acting as an autocrine survival factor (Bachelder et al, 2001(Bachelder et al, , 2002. The importance of VEGF-A in cancer is attested by the use of anti-VEGF antibodies that have shown clinical benefits in colorectal, renal, breast and lung cancer (Hurwitz et al, 2004(Hurwitz et al, , 2005.…”

Combination therapy with zoledronic acid and cetuximab effectively suppresses growth of colorectal cancer cells regardless of KRAS status

“…On the other hand, new chemotherapeutic regimens such as FOLFOX, FOLFIRI, and XELOX have been developed to exert a more potent activity 3, 4, 5, 6. More recently, molecular targeted therapies such as tyrosine kinase inhibitors and monoclonal antibodies have been shown to enhance tumor regression in combination with chemotherapy 7, 8…”