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.