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Colorectal cancer is one of the most common malignancies and a leading cause of death. It is estimated that during 2006 there were 412,900 new cases of colorectal carcinoma diagnosed in Europe and 207,500 deaths.1 The five-year survival of patients with metastatic disease is less than 7%. Hepatic metastases are present in 15-25% of patients at the time of diagnosis of colorectal cancer, and another 15-20% will develop metachronous liver metastases within five years following resection of the primary tumor.2 Progression of liver disease also leads to significant clinical morbidity, which is frequently correlated with overall survival.1 The earlier identification of liver metastases should improve the management and survival of patients with colorectal cancer.1
Unfortunately, only a small proportion - between 10 and 15% - of patients with liver metastases only are primary candidates for potentially curative liver resection, since surgery is limited to those with a good performance status, and those who fall within ‘limited disease criteria’ (generally four or fewer tumors in one lobe of <4cm each, not involving major vascular structures). Of those who do have a complete surgical resection undertaken with curative intent, the five-year survival rate is 30–40%, with at least two-thirds of patients developing recurrent liver metastases within two years after surgery.4 The majority of patients with liver metastases are initially not candidates for liver resection and are managed with systemic chemotherapy; there have been major palliative advances in this field over the last 10 years. Until the mid-1990s the only available drug—which had limited activity in metastatic colorectal cancer—was fluorouracil (5FU). The last decade has seen a rapid evolution of systemic chemotherapies for metastatic colorectal cancer with the development of new cytotoxic agents such as oxaliplatin and irinotecan; oral analogs (Capecitabine; Xeloda® and UFT-tegafur); and targeted biologicals such as bevacizumab (a monoclonal antibody against vascular endothelial growth factor) and cetuximab and panitumumab (monoclonal antibodies against the epidermal growth factor receptor type-1).
Combined with 5FU plus leucovorin (LV), irinotecan-based (FOLFIRI) and oxaliplatin-based (FOLFOX) regimens have evolved as standard first- and second-line treatments for metastatic colorectal cancer (see Table 1). More recently, phase II/III clinical trials have shown that the addition of bevacizumab increases the activity of 5FU/LV, irinotecan combinations,5 and oxaliplatin-based (FOLFOX) regimens.6 Recent trials (XELOXA/NO16966 and CRYSTAL) have suggested that biologicals may not provide the level of added benefit that was originally hoped for.7