Chemotherapy for Colorectal Cancer

Abstract

Colorectal cancer is the most commonly diagnosed cancer in the EU. Various randomised studies have shown a survival benefit with chemotherapy in the adjuvant setting. Adjuvant chemotherapy with 5-fluorouracil/folinic acid (5FU/FA) 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. The latest QUASAR trial results seem to strengthen the argument in favour of adjuvant treatment of Dukes B cancer. Patients with Dukes B tumours and any adverse prognostic indicator should be given the benefit of adjuvant therapy. A number of novel agents (oxaliplatin, irinotecan) showing activity in advanced disease are currently being evaluated in the adjuvant setting. 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. 5FU/FA has been the mainstay of therapy for metastatic colorectal cancer for over 40 years and confers a survival benefit over supportive care. The response rate of 5FU is improved by modulation with FA or by continuous infusional regimens (currently the best expected response rate is around 20-25%). As per the recent National Institute for Clinical Excellence guidelines, the oral agents capecitabine or tegafur with uracil (in combination with FA) can be used as first-line treatment in metastatic colorectal cancer and, although their response rate has not been directly compared to infusional 5FU, survival is unlikely to be inferior. Newer chemotherapeutic agents like irinotecan and oxaliplatin are now entering regular usage due to improved response rates (around 50% in 5FU/FA-containing doublets) and survival. Irinotecan monotherapy is second-line treatment approved by the National Institute for Clinical Excellence, although sequential infusional 5FU/FA irinotecan to infusional 5FU/FA oxaliplatin may convey the best survival with the least side effects. The position of combination chemotherapy before (to downstage) or after metastasectomy (usually from the liver) is still a topic of heated debate. Other routes (intrahepatic, intraperitoneal) are still to be proven and not recommendable outside the trial setting. The latest results of chemotherapy combinations with biological treatments (bevacuzimab and cetuximab) have been very promising indeed. Further improvements in survival, response and quality of life are expected. .