Adjuvant chemotherapy for high-risk stage II and stage III colon cancer: timing of initiation and optimal duration

The benefit of adjuvant chemotherapy has been clearly proven for patients with stage III (node-positive) and high-risk stage II colon cancer and consists to eradicating micrometastases that may be present during the time of surgical resection, reducing thereby the likelihood of disease recurrence and potentially increasing the cure rates after surgery. In this review, the appropriate timing of initiation and optimal duration of adjuvant chemotherapy are discussed. Current guidelines recommend an oxaliplatin-based regimen (FOLFOX: 5-fluorouracil with oxaliplatin or CapeOx: capecitabine with oxaliplatin) instead of 5-FU/LV (5-fluorouracil/leucovorin) for 6 months. For patients with a contraindication to oxaliplatin, a fluoropyrimidine-based regimen alone is an acceptable option. It should be initiated within 6-8 weeks from the time of surgical resection. Studies on reduced duration of fluoropyrimidine-based only regimens (bolus 5-FU/LV vs 5-FU) showed no significant difference in overall (OS) and disease free survival (DFS) benefits. However, the studies showed significantly lower toxicities for protracted venous infusion (PVI) 5-FU given for shorter duration. For oxaliplatin-based therapies, prospective trials failed to establish non-inferiority of 3 months compared to 6 months of oxaliplatin-based adjuvant therapy. The long-term data of the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) collaboration for OS are not mature to date yet. Six months of oxaliplatin-based therapy still remain the standard of care. Decisions to shorten the duration of adjuvant oxaliplatin-based therapy should be dictated by drug tolerability, risk stratification of the disease, consideration of the value of decreased neurotoxicity at the cost of decreased DFS, and patient preference.