Colorectal cancer - drug treatment
From its development in the 1950s until recently, 5-fluorouracil (5-FU) was the drug of choice for the treatment of colorectal cancer. However, in the past five to 10 years, there have been great advances in the treatment of this disease, with the introduction of newer agents such as oxaliplatin, irinotecan and the oral fluoropyrimidines. 5-FU still, however, remains an important drug in the management of colorectal cancer.
This article aims to provide an overview of the drug treatment of colorectal cancer, as well as highlighting future directions for the management of the disease and providing a summary of the relevant National Institute for Clinical Excellence (NICE) guidance.
The initial treatment of colorectal cancer is surgery, but the disease recurs in about half of patients.1 Adjuvant chemotherapy is given after surgery with the aim of “mopping” up any cancer cells that are not removed during the operation.
Because of the proximity to surrounding tissues, the local recurrence rates are generally higher for rectal tumours. The adjuvant treatment of colon and rectal tumours are therefore considered separately. The adjuvant treatment of rectal cancers (usually with a combination of chemotherapy and radiotherapy) is beyond the scope of this article.
By assessing the stage of the tumour at the time of surgery it is possible to identify patients who are more likely to progress either locally or with metastatic disease and thus identify those who are likely to benefit from adjuvant chemotherapy. Patients who are at higher risk of having residual disease or developing metastatic disease are those with stage II or Dukes B2 tumours with full thickness penetration of the bowel wall, or patients with lymph node involvement (stage III or Dukes C). Prognostic factors can also be used to identify patients with a higher risk of recurrence. These include obstruction or perforation of the bowel wall,2 poorly differentiated histology and tumours not demonstrating microsatellite instability [an abnormal number of base pair repeats in regions of DNA which have short repeating segments].3
Although the role of adjuvant chemotherapy for stage III tumours is well established,4 the value of adjuvant chemotherapy for Dukes’ B/stage II disease has not yet been proven.5 This may be due to the good prognosis of patients with stage II disease and the large number of patients who would need to be treated in the context of a clinical trial to show a significant difference in survival. Although there is a lack of evidence to support the use of adjuvant chemotherapy in patients with stage II disease, it may be an option in higher risk patients (eg, those who present with intestinal obstruction or perforation or with a poorly differentiated tumour).5
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Citation: Hospital Pharmacist URI: 10977329
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