CRS, IPC and hepatic resections). Acknowledgements ALF funding from the Uppsala University Hospital was used in the production of this article. Disclosure: The authors declare no conflict of interest.
With roughly 100,000 cases diagnosed yearly, colon cancer is the 4th most frequently diagnosed cancer and the 2nd leading cause of cancer related death in the United States (1). Roughly 80% of cases are Stage I-III thus potentially curable with either surgery alone or combination therapy with surgery and
chemotherapy (2). The 5-year overall survival (OS) for patients with Stage III colon cancer is 60%, however this decreases to 5% in patients with metastatic disease, underscoring the importance Inhibitors,research,lifescience,medical of adjuvant chemotherapy to abolish micrometastatic disease present at the time of curative surgical excision. Multiple randomized controlled trials have established the benefit of 5-fluorouracil (5-FU) (3-5) and capecitabine (6) based regimens in the adjuvant setting for high-risk Stage II and Stage III colon cancer. 5-FU based adjuvant therapy results Inhibitors,research,lifescience,medical in a 5% OS benefit and 10% OS benefit in Stage II and Stage III patients, Inhibitors,research,lifescience,medical respectively, at 8 years (4). Two large, multinational, randomized studies [MOSIAC (7) and NSABP C-07 (8)] PD184352 price showed that adding oxaliplatin to 5-FU/leucovorin
improves disease free survival (DFS) for Stage II/III colon cancer with decreases in relative recurrence risk by 20-23% (7-9). An updated subset analysis of the MOSAIC trial, however, questioned the benefit of the addition of oxaliplatin in low risk stage II patients and the elderly (70-75 Inhibitors,research,lifescience,medical years of age) (10). Based on available data, the NCCN guidelines currently
recommend adjuvant 5-FU +/- oxaliplatin containing regimens for resected high risk Stage II and all Stage III colon adenocarcinoma (11). According to the NCCN, high risk Stage II disease is defined as tumors with poorly differentiated histology (in absence of microsatellite instability), lymphatic, vascular or perineural invasion, bowel obstruction or bowel perforation, close or Inhibitors,research,lifescience,medical positive resection margins, or less than 12 lymph nodes examined. Many questions exist, however, regarding the absolute benefit of adjuvant chemotherapy. For example, most of the adjuvant trials included both Stage II and Stage III patients. Even when patients were sub-divided by stage at time of analysis, data for sub-stages such as Stage IIIA, IIIB and IIIC heptaminol are pooled. Conceivably, there are differences in the benefit of adjuvant chemotherapy between patient sub-groups however the trials are not powered to detect these subtleties. Differences in adjuvant benefit likely also exist based on gene expression profiling however, to date, predictive benefits of therapy for a defined high risk group beyond the NCCN criteria for high risk Stage II and Stage III disease have not been established.