Chemotherapy of colorectal cancer: history and new themes.
Since the clinical introduction of 5-fluorouracil (5-FU) in 1958, improvements in the treatment of advanced colorectal cancer have been modest. However, improvements in response rates have been demonstrated when 5-FU is administered in conjunction with leucovorin, and when methotrexate or trimetrexate is administered preceding 5-FU, indicating that higher response rates could be achieved by biomodulating the activity of 5-FU. Thus, significant emphasis has been placed on designing more effective 5-FU-based combination regimens. Novel agents, including the thymidylate synthase inhibitor raltritrexed and the topoisomerase I inhibitor irinotecan, also have demonstrated activity in colorectal cancer. Other new approaches include the administration of oral 5-FU prodrugs. The development of novel agents, new therapeutic approaches, and the refinement of existing agents and regimens in the clinic will likely improve response rates and, ultimately, patient survival. The history, current treatment options, and future opportunities for advances in chemotherapy for the treatment of colorectal cancer are discussed.
Bertino
J R
JR
Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005467:Floxuridine / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use; D005472:Fluorouracil / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use*; D049673:History, 20th Century; D006801:Humans; D011355:Prodrugs / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use*; D014529:Uridine / Q000031:analogs & derivatives / Q000266:history / Q000494:pharmacology / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D011355:Prodrugs; D005467:Floxuridine; C001943:5-fluorouridine; D005472:Fluorouracil; D014529:Uridine