Current treatments and future perspectives in colorectal and gastric cancer

Given the high rate of distant spread, effective systemic therapy is key to improving survival in patients with colorectal cancer (CRC). The past 40 years have seen progress. The addition of folinic acid (FA) to 5-fluorouracil (5-FU), the use of infusional rather than bolus 5-FU, and the combination of new active agents such as irinotecan and oxaliplatin with 5-FU/FA have each led to an increase in activity. In trials of current combination regimens first-line, response rates (RRs) in excess of 50% and median survival durations longer than 16 months are seen. A recent controlled trial suggests that overall time to progression is maximized and toxicity minimized when an irinotecan/5-FU/FA combination is used first-line, followed by an oxaliplatin/ 5-FU/FA combination on progression. In the adjuvant setting, 5-FU/FA is the standard of care in stage III disease but of uncertain value in stage II patients. The role of new agents such as irinotecan in adjuvant regimens is being assessed. Use of highly active chemotherapy in patients with unresectable disease (particularly liver metastases) achieves responses that allow a subset of patients to proceed to potentially curative surgery. The emergence of novel agents targeted at processes such as tumor angiogenesis will complement cytotoxic chemotherapy, while improved understanding of tumor biology should enable agents to be selected according to the likely sensitivity of the disease in a particular patient. In gastric cancer also, surgery remains the only potentially curative treatment. The extent of dissection required is debated, as is the potential benefit of adjuvant chemoradiotherapy (indeed the degree of resection may interact with the effect of adjuvant treatment). In untreated metastatic gastric cancer, median survival is 3-4 months. This can be increased to around 10 months using chemotherapy. Quality of life is also enhanced. There is no clearly defined standard of care. However, some form of cisplatin/5-FU combination can serve as a reference regimen. As single agents, both irinotecan and docetaxel achieve RRs of around 20% in metastatic CRC. In combination with cisplatin and/or 5-FU a very high and promising RR is achieved. The promise of these agents in combination with 5-FU and 5-FU plus cisplatin is currently being tested in phase III trials.