Clinical overview: adjuvant therapy of gastrointestinal cancer

Adjuvant therapy has been tested widely in the treatment of cancers of the stomach, pancreas, and large bowel. In the USA, the use of postoperative chemoradiation in stomach cancer is considered a standard of care after the publication of the Intergroup Study 0116 in September 2001. This study demonstrated significant benefit in overall and disease-free survival for patients receiving postoperative treatment with fluorouracil (5-FU)/leucovorin chemotherapy and radiation after gastric resection. Adjuvant chemotherapy is not considered to be of significant benefit, and such therapy for patients with resected gastric cancer is investigational. There is interest in the use of neoadjuvant chemotherapy strategies as preoperative treatment followed by surgical resection. This approach has been tested in a randomized study of over 500 patients carried out by the Medical Research Council in the UK. This study demonstrated that patients receiving preoperative and postoperative epirubicin, cisplatin, 5-FU (ECF) chemotherapy, had a downstaging of tumor size, an increase in rates of curative resection, and an increase in disease-free but not overall survival. With pancreatic cancer, there is a controversy over postoperative chemoradiation after pancreatic resection. A recently completed Intergroup Study compared gemcitabine to 5-FU chemotherapy given before and after radiation in resected pancreatic cancer. Over 500 patients have been accrued to this study, which recently closed. In Western Europe, the results of a large clinical trial (ESPAC) have suggested that chemoradiation is not beneficial in patients with resected pancreatic cancer. In large bowel cancer, 5-FU-based adjuvant chemotherapy regimens are superior to surgery alone, particularly in node-positive patients. The use of newer combinations including 5-FU/leucovorin plus irinotecan and 5-FU/ leucovorin plus oxaliplatin are also of interest as chemotherapy in resected colon cancer patients. The recent publication of the MOSAIC trial demonstrated that 5-FU/leucovorin/oxaliplatin (FOLFOX 4) improves progression-free survival in node-positive patients over 5-FU/leucovorin alone. The results of studies of 5-FU/ leucovorin and irinotecan both in Europe (PETACC) and the USA (IFL vs 5-FU/leucovorin) are awaited with interest. Another area of interest in resected colon cancer is the use of molecular genetic monitoring to assess the likelihood of patient relapse. The data over the past several years have demonstrated that patients whose tumors do not have deletion of the deleted in colon cancer (DCC) gene on chromosome 18 have an improved outcome. Recent data are available with tumors that demonstrate microsatellite instability (MSI). Such tumors represent about 15% of all colon cancers and have an improved outcome when compared to those not expressing MSI, and may not benefit from adjuvant chemotherapy.