Abstract
Colorectal cancer (CRC) is a commonly diagnosed malignancy. The prognosis of patients with unresectable, metastatic colorectal cancer (mCRC) is dismal and medical treatment is mainly palliative in nature. Although chemotherapy remains the backbone of treatment, the landscape is changing with the understanding of its heterogeneity and molecular biology. First-line therapy relies on a combination of chemotherapy and targeted therapies, according to clinical patient characteristics and tumor molecular profile. Here we review current evidence from randomized clinical trials for using chemotherapy doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents. Novel therapies developed for small, selected populations are also discussed.
Highlights
Colorectal cancer (CRC) is a commonly diagnosed malignancy and ranks among the three leading causes of cancer death in developed countries
Four randomized clinical trials (RCTs) have shown that first-line oxaliplatin- or irinotecan-based combination CT schedules offer a similar response rates (RRs) of 34–55%, time to progression (TTP) of 7–8 months and median overall survival (OS) of 14–21 months [3]
Bevacizumab provides a significant incremental gain in PFS when it is added to CT regimens such as 5-FU/leucovorin or bolus IFL, but this gain seems to be reduced when it is combined with more active CT schedules like FOLFOX, XELOX or FOLFIRI
Summary
Colorectal cancer (CRC) is a commonly diagnosed malignancy and ranks among the three leading causes of cancer death in developed countries. Despite improvements in screening methodologies, approximately 20% of patients are diagnosed with metastatic CRC (mCRC), which carries a 14% 5-year survival rate. For patients with unresectable mCRC (representing more than 80% of this population), median survival has significantly increased up to 30 months due to advances in multimodal management, modern cytotoxic chemotherapy (CT) and the introduction of targeted agents. Relevant factors for selecting therapy are disease-related characteristics (clinical presentation, tumor burden, resectability and tumor biology), patient-related factors (performance status, age, comorbidity, socioeconomic factors and expectations) and treatment-related factors (toxicity profile and administration schedule). First-line treatment relies on a CT combination, often in association with a biologic agent, according to the individual molecular status. We review current evidence from randomized clinical trials (RCTs) for using CT doublets or triplets, and for the addition of bevacizumab or anti-epidermal growth factor receptor (EGFR) agents, in the first-line treatment of patients with mCRC. Novel therapies developed for small, selected populations are discussed
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