Clinical overview: adjuvant therapy of gastrointestinal cancer

Abstract

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.

A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer

“…However, even in patients presenting with early stage disease, about 60% eventually have local relapse or distant metastases after curative resection [4]. Various adjunctive therapies (such as chemotherapy, radiation therapy [RT], or immunotherapy) have been studied in an attempt to improve survival in patients with resectable gastric cancer [5][6][7]. The role of adjuvant therapies has only recently been clariWed, following the results of three well designed randomized studies with more than 500 patients included in each, all showing a survival beneWt [8][9][10].…”

Novel, isoform-selective, cholecystokinin A receptor antagonist inhibits colon and pancreatic cancers in preclinical models through novel mechanism of action

“…The cell suspension (5 million cells/mouse) was implanted subcutaneously in NSG mice. Once the tumors reached 100-200 mm 3 , the animals were randomized within the respective cell line and treated orally at 50 mg/kg/day. PNB-028 was dissolved in 20% DMSO+80% PEG-300 and administered by oral gavage.…”

“…Cancer cells were implanted subcutaneously in NSG mice and when tumor volume reached 100-200 mm 3 , the animals were randomized and treated with vehicle or 50 mg/kg/day PNB-028 orally. Tumor volume was measured thrice weekly and animals were sacrificed when tumors reached >1,500 mm 3 .…”

“…These cancers are the second and third leading causes of cancer-related deaths in the USA, respectively. Chemotherapy, radiotherapy, and surgery are the only choices available to treat colon and pancreatic cancers (2)(3)(4). Due to failure to diagnose at an early stage, the 5-year survival rate of these cancer patients is much less than that of many other cancers (1,5).…”

Study on the ERCC1 gene polymorphism response to chemotherapy and prognosis of gastric cancer

“…Surgery is the main treatment for early-stage disease, but most of these patients have advanced cancer or have local or distant recurrence by the time of diagnosis (MacDonald, 2004). Therefore, neoadjuvant chemotherapy followed by surgery has become a main treatment method for prolonging the survival of these patients.…”