Metastatic colorectal cancer: first- and second-line treatment in 2005

First-, second-, and third-line therapies for the treatment of metastatic colorectal cancer may influence choices for subsequent therapy. First-line treatment for metastatic colorectal cancer depends largely on combination chemotherapy regimens that have been proven to prolong survival, control disease progression, and improve quality of life, without excessive toxicity. Standard therapies include 5-fluorouracil, irinotecan, and oxaliplatin, but other combination therapies are currently under investigation. An upcoming area of study includes agents that target vascular endothelial growth factor and epidermal growth factor receptor. While doublet therapy is more active than 5-fluorouracil alone, triplet therapy is also emerging. Second-line therapy is dependent upon prior treatment, and second-line FOLFIRI or FOLFOX regimens that incorporate 5-fluorouracil, leucovorin, and either irinotecan or oxaliplatin, respectively, are still in question because of residual toxicities. After combination chemotherapy, a non-cross-resistant chemotherapy is the best choice. Second-line targeted therapy has been well-tolerated and active in several trials. Future developments will most likely occur in the areas of pharmacogenetics (eg, toxicity, age, comorbidities, patient choice, strategy of cure, palliation) and pharmacogenomics (eg, resistance/activity, gene expression) to produce individualized therapies for patients. The type of adjuvant treatment, genomic consideration, and genetic predisposition will be determining factors in the ideal protocol for first-line therapy.