Adjuvant therapy of colon cancer: current status and future developments.

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.