The Colorectal Cancer Coalition: Reflections on the Future

Abstract

Colorectal cancer is the second main cause of cancerrelated death in the Western world. Currently, approximately 75% of patients with colorectal cancer present with locally advanced disease; however, despite curative surgery, around 40% of patients will still experience disease relapse leading to morbidity and eventual mortality. In the postoperative setting, there is now clear evidence that adjuvant chemotherapy significantly improves clinical outcomes in patients with colorectal cancer. Chemotherapeutic drugs such as fluoropyrimidines and oxaliplatin are now used as part of standard care, and the arsenal of new therapies with significant activity in this disease is steadily growing. Nonetheless, the management of patients with potentially curative, locally advanced stage II and III disease remains an active area of clinical debate as the overall combined 5-year survival for these patients is approximately 65%. Indeed, only one third of the 40% of patients who are at risk of relapse derive any significant benefit from adjuvant chemotherapy treatment. Moreover, in the metastatic disease setting, combinations of fluorouracil with agents such as irinotecan and oxaliplatin plus novel targeted agents such as antivascular endothelial growth factor inhibitors, like bevacizumab (Avastin ® ; Genentech, South San Francisco, CA), and epidermal growth factor receptor inhibitors, such as cetuximab and panitumumab, have also led to significantly improved response rates of approximately 45%–50% and improvements in survival in patients with metastatic disease. Therefore, the therapeutic repertoire for patients with colorectal cancer has now expanded to a point where there are many more choices in terms of treatment, clinical trial design, and greater therapeutic impact than ever before. In addition to these therapeutic advances, there have been a number of other important advances over the past decade, such as genomic, proteomic, and imaging technologies that have begun to have significant implications for both clinical and basic research in colorectal cancer as well as patient management. Advances in technology such as gene expression microarrays, high throughput sequencing, and molecular and functional imaging approaches have begun to facilitate the integration of tumor biology and functional data in patient treatment, allowing a better understanding of how the biology of the disease may impact clinical decision making. Nonetheless, for most therapeutic agents, it is still not currently possible to identify those patients most likely to benefit on the basis of their genetic profile nor is it possible to identify those patients who are likely to experience adverse side effects. Clearly, the identification and understanding of these biological factors has the potential to allow oncologists and the drug development process to appropriately select therapeutic agents while adjusting the dose and combination regimen to allow more successful outcomes and avoid significant toxicity and morbidity. In an attempt to address some of these issues, an international Colorectal Cancer Coalition (CCC) was formed to provide an interactive, integrated, and effective international forum in which to openly address these major challenges now facing the colorectal cancer community. The papers presented in this edition of The Oncologist represent a summary of the key presentations and discussions that took place during the inaugural convocation of the CCC. Although concentrating primarily on the impact of novel and recent advances in the treatment of colorectal cancer, as well as the impact of novel targeted therapies and new technologies, participants engaged in in-depth discussion and challenging debate that both identified