Chemo - Who and What?

Dr Anthony Maraveyas FRCP PhD

Colorectal cancer is one of the most common cancers in the UK with an incidence of about 28000 cases per year and causes about 19000 deaths per year. Survival is stage dependent and so is the treatment.

Various randomised studies have shown a survival benefit with chemotherapy in the adjuvant setting. Adjuvant chemotherapy with 5FU/FA(5-fluorouracil/Folinic Acid) for 6 months after curatively resected node positive colon cancer has become the standard practice. However, controversy still exists regarding the optimal regimen and whether to treat node negative patients. A number of novel agents (Oxaliplatin, Irinotecan) showing activity in advanced disease are currently being evaluated in the adjuvant setting. The benefit of adjuvant chemotherapy in Dukes B patients is still under investigation. High-risk patients with Dukes B tumours should probably be given the benefit of adjuvant therapy. Advances in molecular biology have revealed a number of prognostic markers that may refine our treatment algorithms.

5FU/FA has been the mainstay of therapy for metastatic CRC for over 40 years and confers a survival benefit over supportive care. The response rate of 5FU is improved by modulation with folinic acid or by continuous infusional regimens (currently best expected RR around 20-25%). As per the recent NICE guidelines, the oral agents capecitabine or tegafur with uracil (in combination with folinic acid) can be used as first line treatment in metastatic colorectal cancer although their response rate has not been directly compared to infusional 5-FU and is likely to be inferior. Newer chemotherapeutic agents like Irinotecan and Oxaliplatin are now entering regular usage due to improved response rates (around 50%) and survival. Irinotecan monotherapy is the NICE approved second line treatment. A patient with metastatic colorectal cancer should today be expected to have a median survival of 18-20 months compared to that of 11-14 months only a few years ago. The position of combination chemotherapy before (to downstage) or after metastasectomy (usually from the liver) is still a topic of hot debate. Other routes (intrahepatic, intraperitoneal) are still to be proven and not recommendable out-with the trial setting.

The latest results of chemotherapy combinations with biological treatments (Bevacuzimab & Cetuximab) have been very promising indeed. Further improvements in survival, response and quality of life are expected.

We are finally being able to emulate the incremental survival improvements seen for breast cancer throughout the last 15 years in another major cancer. These are exciting times to be treating patients with colon cancer and continuing preclinical and clinical research is required to increase these gains.