The Optimal Duration of Adjuvant Chemotherapy in Colon Cancer

SIMPLE SUMMARY: This review provides an overview of adjuvant chemotherapy in colon cancer over the last 30 years. Key questions address choice of regimen, treatment duration, treatment-dependent toxicity and possible prognostic/predictive factors. Thus, main focus is on the International Duration Evaluation of Adjuvant therapy (IDEA) collaboration which was founded to investigate whether a shortened (3 months) of adjuvant therapy containing a fluoropyrimidine and oxaliplatin is comparable to the current/former standard of care (duration of 6 months). Results of this collaboration will be discussed and evaluated in the context of achieving the best efficacy possible while reducing severe toxicities, and future prognostic/predictive factors. ABSTRACT: Adjuvant chemotherapy for colon cancer (UICC stage II and III) has been under investigation over the last 30 years, regarding treatment duration and regimens. In this review, choice of regimen, its duration, possible limitations and future perspectives are discussed. Monotherapy with 5-fluorouracil was followed by addition of oxaliplatin, resulting in improved 3-yr disease free survival (DFS) and overall survival (OS) rates, but also increased peripheral sensory neurotoxicity (PSN). The International Duration Evaluation of Adjuvant therapy (IDEA) collaboration demonstrated less toxicity, especially PSN, when shortening treatment duration to 3 months. However, formally, the anticipated non-inferiority of 3 months with fluoropyrimidine (FP)/oxaliplatin over 6 months (at 3-yr DFS) was not met for all patients groups, although subgroup analyses showed non-inferiority with capecitabine/oxaliplatin (CAPOX) rather than with FOLFOX, and also in relation to the prognostic information (e.g., clinical low-risk group, pT1-3 N0). In addition, first data of newer parameters like Immunoscore(®) and ctDNA show promising results as stratification parameters. Further investigations to better define clinical risk groups and prognostic factors are mandatory. Besides this, individual decision-making of treatment intensity (FP or FP/oxaliplatin) and duration should always consider patient characteristics and preferences, also given the absolute relatively small differences and their clinical relevance.