Prospective evaluation of fluorouracil chemotherapy based on the genetic makeup of colorectal cancer
- Correspondence to:
Dr J M Carethers
GI Section, 111D, VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA;
Evaluation of 5-fluorouracil chemotherapy and survival, based on mismatch repair (MMR) status, indicates that patients with MMR proficient colorectal tumours benefit from 5-fluorouracil treatment while patients with MMR deficient tumours do not
The current gold standard for treating patients with advanced colon cancer is chemotherapy with 5-fluorouracil (5-FU) based regimens.1 This standard is based on compelling clinical trials utilising 5-FU and levamisole, and demonstrating a survival benefit for patients with TNM stage III (Dukes-Aston Collier stage C) colon cancer.2–4 Although there is no set standard for treating stage II patients, some stage II patients do receive 5-FU chemotherapy, albeit the natural history of this stage of colon cancer is reasonably favourable at more than 70% five year survival.1 Patients with rectal cancer may receive neoadjuvant or adjuvant chemotherapy for stage II or III disease, as treatment in both of these stages of tumour benefit patient survival.1 Stage I patients with colorectal cancer do not receive 5-FU as their prognosis is excellent with removal of the tumour, and stage IV patients may receive 5-FU for palliation. Overall, determination for use of 5-FU based chemotherapy is completely based on the stage of the colorectal cancer in the patient at presentation.
The past decade has brought a fruitful understanding of the genetic and biological behaviour of colorectal cancer, and our knowledge is still growing in this aspect. Colorectal cancer is a genetic disease, with changes in the genome of the tumour cell that are favourable for the tumour’s growth and remote spread. Taking knowledge learned from hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome) in which a germline mutation occurs in genes that encode proteins for DNA mismatch repair (MMR), it was discovered that approximately 15% of sporadic colorectal cancers lack intact MMR due to the epigenetic inactivation …