Molecularly Targeted Therapy for Metastatic Colon Cancer: Proven Treatments and Promising New Agents

摘要

Treatment algorithms and survival for patients with metastatic colorectal cancer have changed dramatically over the past decade, largely due to the advent of molecularly targeted agents. The lessons we have learned with the integration of bevacizumab and cetuximab/panitumumab into standard therapy is that meaningful clinical end points can be achieved, and more patients with metastatic colorectal cancer are being cured or kept alive with a reasonable quality of life due to these new agents. As we enter this second decade of “modern therapy” for metastatic colorectal cancer, an ever-increasing number of new agents aimed at a variety of targets believed to promote cancer cell growth are being tested in clinical trials, and dozens of studies of novel targeted therapies are ongoing. Moreover, during the next decade, we can expect to see an explosion of new agents that will likely improve clinical outcomes further. This review focuses on molecularly targeted agents that are being used regularly in the treatment of colorectal cancer and highlights a number of new agents/targets that are being explored and appear promising in phase I or early phase II trials. Colorectal cancer remains the second leading cause of cancer death in the United States. 1 Survival for patients with metastatic colorectal cancer, however, has improved dramatically over the past decade. In the mid 1990s, the median overall survival (OS) for patients with metastatic colon cancer treated with a 5-fluorouracil (5-FU)-based regimen was only about 12 months. 2 With the addition of irinotecan and oxaliplatin, OS increased to approximately 18 months, 3 but it has really been the addition of biologic agents that led to a substantial jump in OS, which approaches 30 months in some studies. 4 Along with markedly improved OS, a corresponding leap in response rates has occurred, increasing the number of patients oncologists can reconsider as candidates for metastasectomy with potential curative intent. The dramatic benefits seen with biologic agents have spurred a number of ongoing studies examining the benefits of these agents in the adjuvant setting. This review focuses on molecularly targeted agents that are being used regularly in the treatment of colorectal cancer and highlights a number of new agents/targets that are being explored and appear promising in phase I or early phase II trials.