ABSTRACT
Options for the adjuvant therapy of resected stage III colon cancer have expanded
beyond the previously well-accepted standard of 5-fluorouracil (5-FU) combined with
leucovorin. The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) study confirmed that
capecitabine (Xeloda) is at least as effective and is less toxic than a bolus 5-FU
and leucovorin regimen for patients with stage III colon cancer. This study, in addition
to National Surgical Adjuvant Breast and Bowel Project (NSABP) C-06, which demonstrated
the equivalence of tegafur-uracil (UFT)/leucovorin with 5-FU/leucovorin, provides
support for use of oral fluoropyrimidines for adjuvant therapy. Support for use of
multiagent chemotherapy has been provided by the European MOSAIC study, which demonstrated
a significant improvement in 3-year disease-free survival for the addition of oxaliplatin
(Eloxatin) to infusional 5-FU and leucovorin (FOLFOX). Although adding irinotecan
(Camptosar) to a bolus 5-FU and leucovorin regimen did not improve outcome in the
adjuvant setting, the PETACC studies are evaluating the combination of infusional
5-FU, leucovorin, and irinotecan. In contrast to agreement on the appropriateness
of therapy for stage III colon cancer, adjuvant therapy for patients with stage II
disease remains controversial. Future advances in adjuvant therapy may include targeted
therapies. Based on data demonstrating efficacy for the monoclonal antibodies bevacizumab
(Avastin) and cetuximab (Erbitux) in the metastatic setting, clinical trials adding
these agents to standard chemotherapy have been initiated in the adjuvant setting.
Specifically, one U.S. cooperative group trial will evaluate the addition of bevacizumab
to chemotherapy, a second will assess the addition of cetuximab, and a third trial
will evaluate FOLFOX, infusional 5-FU/leucovorin (FOLFIRI), and FOLFOX followed by
FOLFIRI. Finally, a study for patients with stage II disease and adverse prognostic
factors will open. An important consideration in the new clinical trials is an assessment
of molecular markers that either predict response or resistance to therapy or provide
other prognostic information.
KEYWORDS
Colorectal neoplasm - neoplasm metastasis - colorectal neoplasm drug therapy - colorectal
neoplasm therapy
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Michael A MorseM.D.
Division of Medical Oncology, Box 3233, Rm. 3803 Red Zone
Duke South Clinics, Duke University Medical Center
Durham, NC 27710
Email: michael.morse@duke.edu
