Treatment Of Advanced Colorectal Cancer: Current Status And Future Perspectives (pp. 171-208)
Authors: Grivicich, I.; da Rocha, A. B.; Peters, G. J.; Schwartsmann, G, ( VU University Medical Center, Amsterdam, The Netherlands;Universidade Luterana do Brasil, Porto Alegre, Brazil)
Abstract: Colorectal cancer is a common disease with high rate of mortality and very well understood genetics. The majority of patients are diagnosed in an advanced stage of the disease, thus requiring chemotherapy. The prognosis and treatment modality for advanced colorectal cancer depends on the tumor stage, since the accumulation of molecular alterations has been commonly associated with poor prognosis and treatment failure. Although there is evidence of benefit of chemotherapy in adjuvant and metastatic settings, its use still remains unsatisfactory because of intrinsic or acquired drug resistance. The most commonly used protocols in advanced colorectal carcinoma include the antimetabolite 5-fluorouracil (5-FU). Several effective alternative treatment options became available for patients with colorectal cancer who relapse after a 5-FU-based chemotherapy. The introduction of irinotecan and oxaliplatin to the therapy with 5- FU/leucovorin has contributed to increase therapeutic options and to improve response rates and survival. The development of oral agents broadened the treatment options available for patients with this disease. Based on the diversity of molecular behavior of advanced colorectal cancer, a number of new agents entered clinical trials. Among others, cyclooxygenase-2 inhibitors, vascular endothelial growth inhibitors and epidermal growth factor inhibitors, are under investigation. Furthermore, the knowledge of the genetics characteristics can be useful to identify prognostic differences, tumor molecular staging and patient stratification, leading to elect a better treatment modality.