Adjuvant Treatment of Colorectal Cancer

摘要

Many patients with stage III colon cancer, and selected patients with stage II disease, will obtain significant benefit from adjuvant chemotherapy. Combination regimens that include a fluoropyrimidine plus oxaliplatin are the current standard of care, based on findings from the Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) and the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trials. Ongoing randomized trials are evaluating oral fluoropyrimidines combined with oxaliplatin and the addition of targeted therapies to oxaliplatin-based regimens for use in colon cancer adjuvant treatment. Adjuvant treatment approaches for patients with rectal cancer (stage II and III) now include preoperative chemoradiotherapy, based on a phase III comparison of preoperative vs. postoperative chemoradiotherapy conducted in Germany. Ongoing trials are evaluating new cytotoxic and target-oriented agents used in both the neoadjuvant and adjuvant settings in these patients. Improved surgical and radiotherapy techniques may also contribute to superior patient outcomes. Additional research is needed to identify patient subgroups at risk for recurrence, predictive factors for treatment response, and better treatment strategies for patients with colon and rectal cancer. Colorectal cancer (CRC) represents a major public health problem, accounting for more than 1 million new cases diagnosed each year and approximately a half million deaths worldwide. 1 Much work remains to be done to improve outcomes for patients with this disease. The usual diagnostic procedure is endoscopy with biopsy of the tumor. Current preoperative staging procedures include a full medical history and physical examination, blood counts, complete biochemistry profile and serum markers (CEA, CA 19.9), abdominal and pelvic computed tomography (CT) scans, and a plain chest x-ray. In the case of rectal cancer, endoscopic ultrasound and nuclear magnetic resonance (NMR) imaging of the pelvis are required for better tumor (T) or lymph node (N) staging. At diagnosis, 15% of patients present with TNM stages 0 and I, 20%–30% with stage II, 30%–40% with stage III, and 20%–25% with stage IV CRC. A significant decrease in the proportion of patients diagnosed with advanced-stage CRC as well as an increase in overall median survival would be expected if early detection programs were implemented worldwide. A skillful and optimal surgical procedure (R0 resection) is a basic requirement in the management of patients with CRC. In addition to its role in staging, surgical removal of lymph nodes, more specifically the number of nodes removed, has also been directly correlated with patient survival. 2 Despite surgery with curative intent, many patients still have a high risk of tumor recurrence. The search for the most effective strategies, including adjuvant therapy, to eradicate micrometastases is a priority. Another important goal would be the ability to identify those tumors that are not going to recur after surgery. The identification of gene signatures or specific genes that mediate the processes leading to metastasis is a key objective. A set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential has recently been described. 3 Restoring the expression of these microRNAs in malignant cells suppresses metastasis by human cancer cells in vivo. Of these microRNAs, miR-126 restoration reduces overall tumor growth and proliferation, whereas miR-335 regulates a set of genes whose collective expression in a large cohort of human tumors is associated with risk of distant metastasis. 3