Current and emerging therapies for metastatic colorectal cancer: applying research findings to clinical practice.
OBJECTIVE
The results of clinical trials that led to modern first- and second-line chemotherapeutic regimens for metastatic colorectal cancer, including studies of recently introduced monoclonal antibody products that target vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), are described, as well as new therapeutic targets being studied and challenges in research to identify and evaluate new therapies.


CONCLUSIONS
Modern chemotherapy regimens for first-line treatment of metastatic colorectal cancer contain fluorouracil, leucovorin, either oxaliplatin or irinotecan, and the VEGF inhibitor bevacizumab. The EGFR inhibitors cetuximab and panitumumab currently are reserved for second- or third-line therapy, but their role could change as the results of clinical research become available. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin pathway, src kinases, and insulin-like growth factor-1 receptor are among the targets of current research. Identifying the subset of patients with metastatic colorectal cancer who stand to benefit from a particular therapy presents a challenge in conducting clinical research.


CONCLUSIONS
Modern chemotherapeutic and monoclonal antibody regimens have improved survival in patients with meta-static colorectal cancer. The optimal combinations, timing, and sequence of agents remain to be determined.
Hecht
J Randolph
JR
University of California Los Angeles (UCLA) Gastrointestinal Oncology Program, David Geffen School of Medicine at UCLA, 10945 Le Conte Avenue, Los Angeles, CA, USA. jrhecht@mednet.ucla.edu
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D024221:Antineoplastic Protocols; D000068258:Bevacizumab; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D066246:ErbB Receptors / Q000187:drug effects; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D000077150:Oxaliplatin
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D066246:ErbB Receptors; D002166:Camptothecin