The role of pharmacogenetics and pharmacogenomics in improving translational medicine.

The approval of new medicines has slowed significantly over the past years. In order to accelerate the development of new compounds, novel approaches in drug development are required. Translational medicine or research, an emerging discipline on the frontier of basic science and medical practice, has the potential to enhance the speed and efficiency of the drug development process through the utilization of pharmacogenetics and pharmacogenomics. Pharmacogenetics is the study of genetic causes of individual variations in drug response whereas pharmacogenomics deals with the simultaneous impact of multiple mutations in the genome that may determine the patient's response to drug therapy. The utilization of these methods in the drug development process may therefore identify patient sub-populations that exhibit more effective responses and/or an improved benefit/risk profile upon treatment. The authors provide examples of the use of pharmacogenetics and pharmacogenomics in the fields of cardiovascular, pulmonary, oncological, and bone diseases and also highlight the potential economic value of their development.

Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia.

PURPOSE: The concomitant use of intravenous (IV) iron as a supplement to erythropoiesis-stimulating agents in patients with chemotherapy-induced anemia is controversial. This study was designed to evaluate the efficacy and safety of darbepoetin alpha given with IV iron versus with local standard practice (oral iron or no iron). PATIENTS AND METHODS: In this multicenter, randomized, open-label, phase III study, 396 patients with nonmyeloid malignancies and hemoglobin (Hb) less than 11 g/dL received darbepoetin alpha 500 microg with (n = 200) or without (n = 196) IV iron once every 3 weeks (Q3W) for 16 weeks. RESULTS: The hematopoietic response rate (proportion of patients achieving Hb >or= 12 g/dL or Hb increase of >or= 2 g/dL from baseline) was significantly higher in the IV iron group: 86% versus 73% in the standard practice group (difference of 13% [95% CI, 3% to 23%]; P = .011). Fewer RBC transfusions (week 5 to the end of the treatment period) occurred in the IV iron group: 9% versus 20% in the standard practice group (difference of -11% [95% CI, -18% to -3%]; P = .005). Both treatments were well tolerated with no notable differences in adverse events. Serious adverse events related to iron occurred in 3% of patients in the IV iron group and were mostly gastrointestinal in nature. CONCLUSION: Addition of IV iron to darbepoetin alpha Q3W in patients with chemotherapy-induced anemia was well tolerated, resulting in an improved hematopoietic response rate and lower incidence of transfusions compared with darbepoetin alpha alone.