Contents
1. Colorectal carcinoma
   
2. Colorectal metastases to the liver - stage IV no more?

What is colonoscopy?

   
3.

New chemotherapy agents and regimens in colorectal cancer treatment

Role of radiotherapy in colorectal cancer
   
4. Radiological imaging in colonic carcinoma
   
5.

Managing a blocked gut

Care of the ileostomy
   
6.

Molecular biology of colon carcinogenesis
   
  NCC Tumour Board Files
   
  NCC Roundup
   
  Colorectal Cancer
   
 

Pharmacy Tips
   
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New chemotherapy agents and regimens in colorectal cancer treatment

5-fluorouracil (5FU) was introduced in the 1950s for the treatment of colorectal cancers. Since its inception this agent has remained the key agent in active chemotherapy regimens. Different ways of administering 5FU continue to be investigated as treatment for metastases and as adjuvant therapy---eg, comparisons are being made between bolus versus infusional administration, oral prodrug (capecitabine) versus intravenous 5FU, chronomodulated versus conventional. Different new agents have been added to this 5FU backbone, with increased response rates and occasionally survival advantage.
The following is a synopsis of what is considered standard and new in the treatment of colorectal cancers.

Advanced disease
In large prospective randomised trials irinotecan or oxaliplatin added to 5FU and leucovorin (LV) have been shown to yield better response rates (about 50%) than weekly 5FU/LV alone. Overall survival advantage, if any, is modest (about 10 weeks) and found only with the regimen containing irinotecan. But toxic effects and mortality may be increased if the combination of irinotecan/5FU/LV is given in a particular way known as the Saltz regimen. The potential toxic effects are (1) gastrointestinal---severe nausea, vomiting, diarrhoea, and (2) myeloid toxicity and febrile neutropenia and (3) vascular---pulmonary embolism, myocardial infarction and cerebrovascular accidents.
With the introduction of oral capecitabine, the question of whether this agent can be as effective as infusional 5FU (and having the advantage of not requiring central venous access) is being actively investigated. The ideal combination of drugs and way of administration is far from being established, as reflected in the wide range of regimens in use.

Other new molecular agents, alone or added to established regimens, such as cetuximab (a humanised antibody to epidermal growth factor receptor) and bevacizumab (an antibody to vascular endothelial growth factor), are being investigated in clinical trials, either alone or added to established regimens, with promising preliminary results.

Adjuvant setting
For stage 3 colon cancer, adjuvant treatment with 5-FU/LV for 6 months after curative surgery is the standard of care. Elderly patients of good performance status benefit equally from adjuvant 5FU-containing chemotherapy. There are several trials investigating the adjuvant use of irinotecan and oxaliplatin. Preliminary results from one such trial show that the combination of oxaliplatin/5FU/LV (FOLFOX 4 regimen) improves disease-free survival. Our centre is participating in an international multicentre trial studying the role of oxaliplatin and oral capecitabine (XELOX regimen) as adjuvant therapy.

The strides being made daily towards incremental gain in survival and improved efficacy with new agents that are well tolerated in colorectal treatment provide optimism for the possible “retirement” of 5FU after almost half century of unrivalled primacy.

Dr Donald Poon
Registrar
Medical Oncology

Dr Simon Ong
Consultant
Medical Oncology

 

Role of radiotherapy in colorectal cancer
 
Most cases of colorectal cancer require surgery for complete cure. Radiation and chemotherapy are sometimes used as adjuvant treatment after surgery to reduce risk of recurrence.

Data from series reporting on adjuvant radiotherapy for colon cancer are largely retrospective. The most comprehensive findings came from Massachusetts General Hospital. There certain groups of patients benefited from postoperative radiotherapy. Patients with locally advanced disease (AJCC stage T4), those with perforation or fistulas, and those with subtotal resection showed a significant improvement in local control and disease-free survival. This advantage was obtained at the expense of increased likelihood of acute and late bowel complications. A recent American Inter-group trial, INT0130, which randomised patients with node-positive locally advanced colon cancer to adjuvant chemotherapy with or without radiotherapy, closed prematurely due to poor patient accrual and did not show any overall survival benefit between the two arms.

Unlike colon cancer, in rectal cancer local recurrence is a major component of relapse. The recurrence commonly produces symptoms. Surgical salvage procedures usually have to be extensive and are often not possible. The desired effect of adjuvant radiotherapy is to reduce local recurrence and improve overall survival. Reduction in local recurrence has been well documented but improvement in overall survival has proved rather elusive.

Neoadjuvant radiotherapy is used to facilitate surgery or shrink disease preoperatively and eliminate small-volume locoregional disease. This can be given as a 1-week course (Swedish) or a 5-week course (North American). The Swedes found that short-course treatment improved local control and overall survival, but their results have not been reproduced by other centres. For example, a Danish trial of the short- course regimen did not show any downstaging. In Singapore, the protracted course is often given concurrently with chemotherapy, to downstage locally advanced rectal cancers to facilitate surgical excision.

Radiotherapy after potentially curative surgery is given for Dukes stage B2 and C rectal cancer because local failure is higher (25 – 50%) in these patients than in those with earlier stages. In randomised trials comparing postoperative radiotherapy with surgery alone, postoperative radiotherapy decreased local failure but not overall survival rates. The addition of chemotherapy to radiotherapy also improves local control. 5-fluorouracil has been given with radiotherapy in different formulations and regimens, with substantial benefit being obtained with protracted venous infusions. Oral formulations given concurrently with radiotherapy have been well tolerated. Trials in progress are comparing preoperative with postoperative radiotherapy, as well as the addition of new chemotherapeutic agents, such as capecitabine and oxaliplatin.

Dr Michael Wong
Registrar
Therapeutic Radiology