What is the efficacy of adjuvant chemotherapy for stage II colon cancer?

Updated: Apr 15, 2020
  • Author: Tomislav Dragovich, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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A large European trial (QUASAR) demonstrated small but significant benefit (3.6%) in terms of absolute 5-year survival rate for those patients who received fluorouracil/leucovorin versus those in the control group. [69] In contrast, a study by O’Connor et al found that in Medicare patients with stage II colon cancer, with or without poor prognostic features, overall survival was not substantially improved by adjuvant chemotherapy. [95]

Ongoing adjuvant trials are investigating additional risk stratification of stage II colon cancer based on clinicopathological and molecular markers. For example, the ECOG 5202 trial is comparing two forms of adjuvant therapy (oxaliplatin, leucovorin, and fluorouracil with or without bevacizumab) in high-risk patients, with low-risk patients undergoing observation only.

In this trial, high-risk patients are defined as those with microsatellite stability (MSS) or low-frequency microsatellite instability (MSI-L) and loss of heterozygosity at 18q. Low-risk patients are those with MSS or MSI-L and retention of 18q, or high-frequency MSI with or without loss of heterozygosity at 18q.

Detection of MSI has become important for treatment for metastatic colorectal cancers with MSI, as these cases respond favorably to biologic therapy with immune checkpoint inhibitors (eg, pembrolizumab, nivolumab). These tumors tend to have high expression of checkpoint proteins, including programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), which interfere with the body’s antitumor T-cell response. By disabling these proteins, checkpoint inhibitors enable T cells to kill tumor cells. [96]

A comparison of 3 vs 6 months of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) adjunct chemotherapy in 1254 patients with high-risk stage II resected colorectal cancer found that neurotoxicity was approximately 5 times lower in the 3-month arm than the 6-month arm. Noninferiority of 3 months of therapy was not shown for 5-year relapse-free survival. However, a possible regimen effect was observed, suggesting that either 3 months of CAPOX or 6 months of FOLFOX therapy can be used when an oxaliplatin doublet is indicated for treatment of patients with stage II colorectal cancer. [97]

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