Irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer

Out of every 17-18 individuals in the US, one develops colorectal cancer (CRC) in their lifetime. Of individuals diagnosed with CRC, > 50% present or develop metastatic disease, which, if untreated, is associated with 6-9 months median survival. Although surgical resection is the primary treatment modality for CRC, chemotherapy is the mainstay of treatment for metastatic or unresectable disease. For nearly three decades, 5-fluorouracil (5-FU) has been the chemotherapy of choice for treatment of CRC. However, the response rates to single 5-FU therapy have been suboptimal with an objective tumour response of 10-20%. Attempts have been made to improve the efficacy of 5-FU by either schedule alteration (protracted infusion versus intravenous push) or biochemical modulation with leucovorin (LV). Continuous infusion induced more tumour regression and prolonged the time-to-disease progression with some significant impact on survival (11.3 versus 12.1 months; p < 0.04). 5-FU/LV resulted in a significant increase in overall response rates and in the prolongation of disease-free survival in the adjuvant setting, although severe toxicities represent a major clinical problem. The last 10 years have seen the addition of several new agents such as irinotecan, oxaliplatin, raltitrexed, bevacizumab and cetuximab. The prognosis has significantly improved with the addition of these agents, with median survivals now > 20 months. This review paper focuses on irinotecan, oxaliplatin and raltitrexed when used alone and in combination.