Individualizing chemotherapeutic treatment of colorectal cancer

Abstract

Patient-specific factors that enter into decisions about the chemotherapy used to treat colorectal cancer are illustrated in several case studies. Genetic polymorphisms in genes that encode drug-metabolizing enzymes may affect the disposition and the risk for toxicity from chemotherapy agents used to treat colorectal cancer. Severe toxicity from 5-fluorouracil has been attributed to a deficiency in dihydropyrimidine dehydrogenase (DPD), but currently there is no widely used genetic test for DPD deficiency. An assay is available for genotypic testing of the enzyme UGT1A1, which is predictive of toxicity from irinotecan. Advanced age, prior pelvic or abdominal radiotherapy, a poor performance status, and increased pretreatment total bilirubin concentration also are associated with irinotecan-related toxicity. A reduction in irinotecan dosage or use of an alternative agent may be warranted in patients with risk factors for toxicity. Positive epidermal growth factor receptor (EGFR) expression by immunohistochemical (IHC) staining does not necessarily predict the response to cetuximab, a monoclonal antibody that binds EGFR, possibly because of the low sensitivity of the test. Carcinoembryonic antigen (CEA) is the tumor marker of choice for monitoring for progression of colorectal cancer. Individualizing chemotherapy based on disease stage, pharmacogenetics, prior therapy, patient age, performance status, and CEA level may help to optimize outcomes from chemotherapy for patients with colorectal cancer.