Therapeutic strategy in unresectable metastatic colorectal cancer

Abstract

While surgery is the cornerstone treatment for early-stage colorectal cancer, chemotherapy is the first treatment option for metastatic disease when tumor lesions are frequently not fully resectable at presentation. Mortality from colon cancer has decreased over the past 30 years, but there is still a huge heterogeneity in survival rates that can be mainly explained by patient and tumor characteristics, host response factors, and treatment modalities. The management of unresectable metastatic colorectal cancer is a global treatment strategy, which applies several lines of therapy, salvage surgery, maintenance, and treatment-free intervals. The individualization of cancer treatment is based on the evaluation of prognostic factors for survival (serum lactate dehydrogenase level, performance status), and predictive factors for treatment efficacy [Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status]. The available treatment modalities for metastatic colorectal cancer are chemotherapy (fluoropyrimidine, oxaliplatin, irinotecan), anti-angiogenic agents (e.g. bevacizumab), and anti-epidermal growth factor agents (cetuximab, panitumumab). The increasing number of active compounds dictates the strategy of trials evaluating these treatments either in combination or sequentially. Alternative outcomes that can be measured earlier than overall survival are needed to shorten the duration and reduce the size and cost of clinical trials.

Keywords: chemotherapy; clinical trial; colorectal cancer; molecular targeted therapy.

Conflict of interest statement

The authors declare no conflicts of interest in preparing this article.

Figures

Figure 1

Examples of treatment strategies for metastatic colorectal cancer. CFI, chemotherapy-free interval; chemo, chemotherapy; PD, progression disease.

Figure 2.

Treatment options in unresectable wild-type Kirsten rat sarcoma viral oncogene homolog (KRAS) metastatic colorectal cancer. CT, chemotherapy; EGF, epidermal growth factor. Study acronyms are used for brevity: readers may refer to the cited references in the text for full details of study names and details. OPTIMOX (Tournigand et al., 2006); CONcePT (Grothey et al., 2008); AVF2107g (Hurwitz et al., 2004); PRIME (Douillard et al., 2010); CRYSTAL (Van Cutsem et al., 2009); 181 (Peeters et al., 2010); FOLFIRI3 (Mabro et al., 2006); E3200 (Giantonio et al., 2007); BRITE (Grothey et al., 2008); VELOUR (Van Cutsem et al., 2011); BOND (Cunningham et al., 2004).