ABSTRACT

References .......................................................................................................................... 543

Adenocarcinoma of the colon and rectum is a growing health problem around the world and

accounts for most cases of colorectal cancer. Approximately two-thirds of such tumors arise

in the colon and one-third in the rectum. According to recent estimates, nearly one million

people are diagnosed with colorectal cancer each year, and almost half a million die from this

disease worldwide.1 Colorectal cancer is associated with the adoption of a so-called Western-

ized lifestyle, and the disease is more common in developed areas of the world. Fortunately,

the relatively long course of colorectal tumorigenesis allows for early detection and effective

interventions that aim at reducing morbidity and mortality.2 Unfortunately, only a small

proportion of eligible individuals currently undergo screening for colorectal cancer.3 In the

United States, where the lifetime risk of colorectal cancer is currently 1 in 17,4 it was estimated

that approximately 145,000 cases would be diagnosed in 2005.5 Although only one in five

patients with colorectal cancer has metastatic disease at diagnosis,5 systemic recurrence will

develop in a significant proportion of patients who have colorectal cancer that invades

through the mucosa or the regional lymph nodes (i.e., tumor-node-metastasis stages II

and III) at diagnosis. For patients with such recurrences, systemic therapy offers the potential

to prolong survival and improve the quality of life.6,7

During the past decade, systemic therapy for colorectal cancer has evolved significantly.

Two novel chemotherapeutic agents, irinotecan and oxaliplatin, have been shown to improve

on the previous standard of fluorouracil (5-FU) and leucovorin.8-11 More recently, antian-

giogenic agents and other molecularly targeted therapies have been investigated in clinical

trials among patients with colorectal cancer. In this chapter, we provide a brief overview

of the state of the art regarding systemic therapy for advanced colorectal cancer, discuss the

role of angiogenesis in colorectal cancer biology, present recent findings from studies of

antiangiogenic agents, and discuss future perspectives relating to antiangiogenic treatment

for colorectal cancer.