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SYSTEMIC
THERAPY OF COLORECTAL CANCER
Štabuc
B.
University
Medical Center Ljubljana, Department of gastroenterology, Ljubljana,
Slovenia
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ABSTRACT
Colorectal
cancer alone accounts for around 200,000 deaths in Europe and represents
a significant health problem. Although about fifty percent of patients
are cured by surgery alone, the other half will eventually die due
to metastatic disease, which includes approximately 25% of patients
who have evidence of metastases at the time of diagnosis. Surgical
resection of the primary tumor and regional lymph nodes is the only
curative therapy for colorectal cancer. However, adjuvant chemotherapy
in stage III colon cancer following curative resection has been
shown to reduce the risk of recurrence by 19-40% and of death by
16-33%. 5-fluorouracil and leucovorin given for six months may represent
the best adjuvant treatment available today. The contribution of
levamisole to adjuvant treatment seems to be marginal, if any. The
benefit of adjuvant chemotherapy for the patients with Dukes B colon
cancer is less clear. A meta-analysis of 1,381 patients with advanced
colorectal cancer showed a significant increase in response rate
with the bolus 5-fluorouracil and leucovorin versus 5-fluorouracil
alone, but no significant difference in median survival. Continuous
infusion allows higher doses of 5-FU than rapid bolus infusion and
improves response rate, survival and time to progression. Oral fluoropyrimidines
(capecitabine and uracil / tegafur (UFT)) are as active as intravenous
fluoropyrimidines. Compared to intravenous 5FU, oral fluoropyrimidines
have safety advantages, clinical benefits and are more convenient
for patients. Phase III randomized clinical trials in patients with
metastatic colorectal cancer demonstrate the significant superiority
of combining irinotecan with 5-fluorouracil and leucovorin or oxaliplatin
with 5-fluorouracil and leucovorin over the same 5-fluorouracil
and leucovorin alone. Several phase II studies have shown that the
combination of the oral fluoropyrimidines plus irinotecan or oxaliplatin
is very active in metastatic colorectal cancer. Trials with agents
acting on novel targets in colorectal cancer are progressing rapidly,
including doxifluridine, new inhibitors of thymidylate synthase
(ZD9331), oral camptothecins (Rubitecan), multitarget antifolate
antimetabolite (Premetrexet), inhibitors of epidermal growth factor
receptor (Cetuximab), COX-2 inhibitors (celecoxib) and farnesyltransferaze
inhibitors (Zarnestra). However, a few randomized trials failed
to show a survival advantage compared with placebo in patients with
advanced refractory colorectal cancer. |
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Keywords:
Colorectal cancer, Systemic therapy, Chemotherapy |
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