Symptom Relief With Cetuximab for Patients With Metastatic Colorectal Cancer

Introduction

Colorectal cancer remains a major public health problem in most developed countries. In Europe, it is the third most common cancer in men and the second in women. In the United States it is estimated that 147,000 patients were diagnosed with colorectal cancer in 2009. When diagnosed in early stages, survival rate at 5 years is up to 90%; however, in metastatic disease 5-year survival rates are still very poor.

Abstract

The introduction of novel targeted therapies in the management of metastatic colorectal cancer (mCRC) has modified the natural history of this disease in the last years. New compounds with antiepidermal growth factor receptor (EGFR) or antiangiogenic activity have been progressively introduced to the clinical practice. Among these, cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligandbinding domain EGFR has demonstrated antitumor activity in monotherapy or in combination with chemotherapy. Up to 80% patients with metastatic colorectal cancer have unresectable disease. Therefore, palliation is the main aim in the management of these patients. Progression-free survival (PFS) is a valid endpoint for trials in the palliative setting in mCRC. Other endpoints, frequently considered as secondary endpoints such as response rate (RR) or overall survival (OS) are also very important. However, improvement of quality of life (QoL) and appropriate symptom management are major issues in the therapeutic strategy and these are occasionally considered in some trials.

Recent retrospective data indicate that KRAS mutation status has an important role as a predictive factor for response to anti-EGFR therapy. Treatment with cetuximab in patients with KRAS mutated tumor has no benefit or might be even deleterious in combinations with oxaliplatin.

This review summarizes the most important achievements in the issue of symptomatic control and palliation induced by cetuximab therapy and provides a brief overview about the main clinical trials assessing its benefit in addition to different chemotherapy schedules and the role of KRAS mutational status as predictive factor for response.

Keywords

Cetuximab, advanced colon cancer, EGFR