Adjuvant medical therapy for colorectal cancer

In the mid-1980s, trials of adjuvant therapy for colon cancer in the United States had a "no treatment" arm, which reflected the belief that effective adjuvant chemotherapy did not exist for patients with surgically resected disease at high risk for recurrence. However, with the observation in the early 1990s that postsurgical adjuvant 5-FU plus levamisole reduced tumor recurrence and ultimately increased overall survival in stage III colon cancer, the potential of effective adjuvant chemotherapy was realized. Questions about the duration of adjuvant chemotherapy, the specifics of chemotherapy schedule/drug selection, and its use in stage II colon cancer are beginning to be clarified in large, randomized adjuvant therapy trials. In rectal carcinomas, combined modality postoperative pelvic irradiation plus chemotherapy for stage II and III disease has been shown to reduce both local and systemic recurrences and to prolong survival compared with that in patients treated with local surgery and radiation. Again, large randomized trials are attempting to clarify both the optimal chemotherapeutic agents and schedules to be used and also whether preoperative combined modality therapy can improve the resectability rate, rate of sphincter preservation, and survival. Future trials will examine new agents shown to be effective in advanced disease as well as monoclonal antibodies, such as MoAb 17-1A, that may have selective activity in minimal disease. Improvement in overall survival remains the ultimate endpoint of future adjuvant therapy trials; however, trials will also critically examine toxicity, quality of life, pharmacoeconomics, and genetic and biologic correlates that may help select more appropriate candidates for adjuvant therapies.