- Rachel S J Midgley,
- D J Kerr
Despite substantial improvements in surgical technique and postoperative care, colorectal cancer continues to kill 95 000 people in Europe alone each year.
Adjuvant—helpful, assisting, auxiliary (from Latin ad to, and juvare to help)
Of the annual 150 000 newly diagnosed cases, about 80% have no macroscopic evidence of residual tumour after resection. More than half of patients, however, develop recurrence and die of their disease. This is a result of occult viable tumour cells that have metastasised before surgery and which are undetectable by current radiological techniques (the limit of detection of standard computed tomography is about 1cm3, equivalent to 109 cells).
Adjuvant treatment (chemotherapy and radiotherapy) has developed as an auxiliary weapon to surgery and is aimed at eradicating these micrometastatic cancer cells before they become established and refractory to intervention. As the presence of the primary tumour can exert an inhibitory influence on micrometastases, theoretically the removal of the tumour might stimulate growth of any residual cells, increasing the proliferating fraction and rendering them more susceptible to the cytotoxic effects of the widely used cytotoxic agent, fluorouracil.
It is reasonable to predict therefore that the earlier chemotherapy is started after surgery, the greater the potential benefit, although this has not yet been formally addressed in adjuvant trials. Implicit in this belief is a necessity for a multidisciplinary effort between surgeon, oncologist, and the community care team to provide seamless, streamlined cancer care for the individual patient.
Pharmacology of fluorouracil
Fluorouracil has remained the cornerstone chemotherapy for colorectal cancer for over 40 years. It is a prodrug that is converted intracellularly to various metabolites that bind to the enzyme thymidylate synthase, inhibiting synthesis of thymidine, DNA, and RNA. Increasing understanding of the molecular pharmacology of fluorouracil …