Colorectal carcinoma: Current problems and future perspectives

Abstract

Colorectal carcinoma represents a highly interesting model for the biological development of a solid tumor, the efficacy or primary and secondary prevention and the development of chemotherapeutic and immunologic strategies for adjuvant and/or neoadjuvant treatment in resectable stages. Adjuvant systemic 5-FU/levamisole is currently the standard adjuvant treatment for stage III colon cancer. 5-FU/folinic acid for 6 months seems to achieve equivalent results. Continuous infusion of 5-FU for 7 days postoperatively via the portal vein achieves also a comparable improvement in disease-free and overall survival. Beyond the long term systemic as well as short time intraportal chemotherapy, adjuvant immunotherapy with either 17-1A murine monoclonal antibody or autologous tumor vaccine achieves quite comparable results like adjuvant chemotherapy. Therefore the combination of these modalities might be of high interest for further investigation. The current EORTC study for ctal cancer investigates the role of the combination of short time regional and long term systemic chemotherapy. For rectal cancer stage II and III adjuvant 5-FU plus radiation is currently the standard. However, further improvement seems possible with 5-FU given as continuous infusion during radiation; this approach is currently investigated in an ongoing Intergroup study. A further attractive approach, particularly for locally advanced, borderline resectable rectal cancer is the neoadjuvant combined modality treatment with 5-FU/folinic acid plus radiation followed by surgery and further adjuvant chemotherapy; this neoadjuvant treatment is currently being investigated in comparison to postoperative 5-FU/folinic acid plus radiation in an ongoing Intergroup study. Future protocols should also include immunotherapy with 17-1A antibody which significantly prolongs disease-free and overall survival also in rectal cancer. Since only a minority of patients benefit from these perioperative treatment modalities, a better selection of patients with high risk for recurrence and major benefit from adjuvant treatment is required. Beyond histopathologic investigations and pathological staging, molecular biologic investigations with determination of LOH in chromosome regions covering a candidate tumor suppressor gene or of overexpression of certain oncogenes and growth factors, might be more appropriate prognostic factors for a detailed description of the potential risk for recurrence. These molecular genetic investigations are an essential part of further clinical trials for adjuvant treatment strategies. Future adjuvant treatments will target to the most relevant molecular genetic aberrations in the primary tumor. A more selective and particularly more specific adjuvant treatment with perhaps further improvement of survival can be expected from these ongoing investigations.