Current Status of Adjuvant Therapy for Colon Cancer

摘要

Due to its frequency and persistently high mortality, colorectal cancer represents a major public health problem. The use of adjuvant chemotherapy has improved prognosis in stage III disease, but much work remains to be done in optimizing adjuvant treatment, including refinement of ability to predict disease course and response to chemotherapy. The FOLFOX4 regimen is now considered standard treatment for stage III disease. Combinations of irinotecan and 5-fluorouracil (5-FU) have not proven to be more effective than 5-FU/folinic acid (FA). Oral fluoropyrimidines (eg, capecitabine, UFT + FA) now offer an alternative to intravenous 5-FU. Adjuvant chemotherapy for stage II colorectal cancer is more controversial. Use of adjuvant chemotherapy does not appear to be justified in patients with no particular risk factors (T3N0 with no poor prognosis factor). In contrast, the risk:benefit ratio in patients with one or more poor prognostic factors (T4 tumor, occlusion or perforation, poorly differentiated tumor, vascular invasion, or 1 Colon cancer and other supraperitoneal malignancies (tumors located at the rectosigmoid junction or in the upper part of the rectum) present a low risk of local recurrence, and radiotherapy is consequently not indicated. The mortality risk associated with colon or supraperitoneal rectal cancers is, therefore, related primarily to risk of metastasis. Systemic treatments can diminish risk of metastasis by eradicating disseminated microscopic tumor foci that are distant to the primary tumor and undetectable during preoperative and perioperative assessment of tumor extension. In the absence of any further treatment after resection of the primary tumor, 5-year survival rates are principally determined by the histologic stage of the tumor at the time of resection. The crucial prognostic factor for the survival of patients with no visceral metastases is the stage of the tumor, 2 determined by the depth of tumor penetration into the intestinal wall and the number of lymph nodes involved. The therapeutic potential of systemic treatments for colorectal cancer has expanded rapidly during the past 10 years, with the introduction of oral fluoropyrimidines, oxaliplatin, and irinotecan. The marked improvements in response rate, progression-free survival (PFS), and overall survival (OS) achieved with these new cytotoxic agents in patients with metastatic colorectal cancer 3 , 4 encouraged their testing in the adjuvant treatment of nonmetastatic disease, especially in patients with stage III tumors. At the same time, advances in tumor biology led to the discovery of prognostic factors, such as microsatellite instability (MSI), that are potentially predictive of tumor response to cytotoxic agents. Prognostic factors are particularly valuable in the context of stage II colorectal cancer, in which the benefit of adjuvant cytotoxic therapy is more controversial than in stage III disease. This article reviews the status of adjuvant treatment for stage II and III colon cancer on the basis of data available as of 2006. Since initial prognosis of the disease is crucial to selecting the optimal treatment for each patient, the first part of the review focuses on the factors identified to date as being predictive of disease outcome and, in some cases, response to treatment.