Advances in Chemotherapy against Advanced or Metastatic Colorectal Cancer

Abstract

In the early 1990s, some prospective controlled trials revealed the superiority of chemotherapy for survival compared with best supportive care for advanced or metastatic colorectal carcinoma. Until recently, 5-fluorouracil (5-FU) and leucovorin (LV) were the standard therapies against advanced or metastatic colorectal cancer. Theoretically, LV should increase the antitumor activity of 5-FU, although this effect of LV addition has been controversial. A meta-analysis which analyzed 21 randomized controlled trials revealed that a combination of 5-FU and LV doubled the response rate compared with 5-FU alone (from 11 to 21%) and prolonged the median survival time by about 1 month (from 10.5 to 11.7 months). Chemotherapy against advanced or metastatic colorectal cancer has steadily advanced after the introduction of triplet regimens containing 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11) and (trans-R,R-1,2-diamine cyclohexane)oxalatoplatinum(II) (L-OHP). For LV/5-FU/CPT-11, the regimen in which 5-FU is administered with continuous infusion (FOLFIRI) is preferred compared with the 5-FU bolus infusion. According to the results of the randomized controlled trial comparing FOLFIRI followed by FOLFOX6 and the reverse sequence, FOLFOX6 followed by FOFIRI, in the treatment of advanced colorectal cancer, FOLFIRI and FOLFOX are now considered to have almost the same efficacy in the treatment of advanced or metastatic colorectal cancer. FOLFIRI followed by FOLFOX or FOLFOX followed by FOLFIRI provide a median survival time of about 21 months in advanced or metastatic colorectal cancer. Both an anti-vascular endothelial growth factor monoclonal antibody, bevacizumab, and an anti- epidermal growth factor receptor monoclonal antibody, cetuximab, should prolong the survival of advanced or metastatic colorectal cancer by 2–3 months in combination with FOLFIRI or FOLFOX. However, from the viewpoint of medical economics, because of the high acquisition costs in relation to clinical benefits, antibodies are unlikely to represent a cost-utility solution. New agents, including macromolecule agents, small-molecule agents and vaccines, will be introduced alongside chemotherapy against colorectal cancer. Subsequently, clinical researchers will have to consider the cost-utility of these agents.