BEYOND KRAS: Other Markers and Potential Treatment Strategies for KRAS Mutant and Wild-type Patients.
Summary of "BEYOND KRAS: Other Markers and Potential Treatment Strategies for KRAS Mutant and Wild-type Patients."
OPINION
STATEMENT:
Despite the advances and new drug discoveries, the best drug in metastatic colorectal cancer (mcrc) is 5-fluorouracil. This drug is the backbone of FOLFOX and FOLFIRI which are the standard first line cytotoxic regimens in the metastatic setting. The efficacies of these two regimens are equivalent, and the selection of one over the other is largely based on the side effect profile. Bevacizumab is commonly added to each of these regimes in the first line setting. When a patient develops progression of disease on FOLFOX, then treatment with either single agent irinotecan, or FOLFIRI is a typical approach. If FOLFIRI-BEV is used in first line, the FOLFOX is typically given in second line. All patients with metastatic colorectal cancer have their tumor tested for the KRAS mutation in exon 2. If the tumor is KRAS wild-type then either cetuximab or panitumumab, with or without continued irinotecan, may be used. In patients whose tumors are symptomatic, and so requiring a rapid response, cetuximab or panitumumab may be incorporated into second line therapy instead of third line. There are no data supporting the use of cetuximab after progression on panitumumab or vice versa and use of one of these agents after failure on the other is not appropriate. Upon progression on the standard chemotherapies outlined above appropriate patients may be offered participation in a clinical trial. For patients whose tumors are KRAS mutant a clinical trial should be considered upon progression on oxaliplatin and irinotecan-based regimens. New agents and combinations of targeted therapies described below offer promising therapies for patients with both KRAS wild type and mutant tumors. As our molecular knowledge of mcrc advances future therapies will likely tailor an individualized approach based on tumor specific molecular markers.
Affiliation
Colorectal Oncology Section, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 264, New York, NY, 10065, USA, cerceka@mskcc.org.
Journal Details
This article was published in the following journal.
Name: Current treatment options in oncology
ISSN: 1534-6277
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21472513
- DOI: http://dx.doi.org/10.1007/s11864-011-0147-3
Medical and Biotech [MESH] Definitions
Monitoring, Immunologic
Testing of immune status in the diagnosis and therapy of cancer, immunoproliferative and immunodeficiency disorders, and autoimmune abnormalities. Changes in immune parameters are of special significance before, during and following organ transplantation. Strategies include measurement of tumor antigen and other markers (often by RADIOIMMUNOASSAY), studies of cellular or humoral immunity in cancer etiology, IMMUNOTHERAPY trials, etc.
Genome-wide Association Study
An analysis comparing the allele frequencies of all available (or a whole GENOME representative set of) polymorphic markers in unrelated patients with a specific symptom or disease condition, and those of healthy controls to identify markers associated with a specific disease or condition.
Potentiometry
Solution titration in which the end point is read from the electrode-potential variations with the concentrations of potential determining ions. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Tumor Markers, Biological
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Potassium Channels, Voltage-gated
Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.
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