Drug treatment of colorectal cancer. Current status

Drug therapy is most often used in colorectal cancer for palliation of metastatic disease. Current data also support the use of adjuvant chemotherapy following complete surgical resection in patients with locoregional lymph node metastases. The agent most widely used in the treatment of colorectal cancer is the antimetabolite fluorouracil (5-fluorouracil; 5-FU). This fluoridated pyrimidine has been available for over 30 years, yet to date no other single agent has proven to be more efficacious. Controversy exists about the most desirable schedule for administration of fluorouracil. Efforts have been made to improve upon its therapeutic index and efficacy by using the concept of biomodulation, in which chemicals which are not themselves active antineoplastic agents against colorectal cancer are administered with fluorouracil in an attempt to enhance the sensitivity of the cancer cell to fluorouracil. Biomodulation agents currently in use in clinical practice include leucovorin (calcium folinate), methotrexate, and interferon-alpha. Other biomodulation strategies are currently under investigation. Adding putatively active antineoplastic agents to fluorouracil to form combination chemotherapy regimens has not yielded convincingly superior results to treatment with fluorouracil alone, and the toxicities of many of these combination regimens have been formidable. Secondary therapies following failure of fluorouracil-based regimens have been similarly disappointing. Current areas of investigation into the chemotherapy of colorectal cancer include development of new agents, locoregional administration of chemotherapy, and manipulation of intrinsic drug resistance mechanisms of the cancer cells.