Pharmaceutical Investigation for Individualized and Optimal Cancer Pharmacotherapy.

Abstract

After the year 2000, the treatment of cancer remarkably changed, including the development of outpatient cancer chemotherapy. Meanwhile, we have encountered many clinical problems related to cancer patient pharmacy services. To resolve these problems, I have tried to establish the individualized and optimal cancer pharmacotherapy utilizing the findings of basic research. In this review, three topics of my research will be introduced. 1) In 2005, information regarding the genetic polymorphism of UGT1A1*28 was described in the package insert of the drug irinotecan in the United States. At that time, however, there was little similar information for Japanese patients. Through clinical research, we demonstrated that UGT1A1*6 was a significant factor for neutropenia, as induced by irinotecan. 2) Tyrosine kinase inhibitors are mainly used at a fixed dose, but wide interpatient variability has been observed relative to their pharmacokinetics and/or pharmacodynamics. To overcome these variations, clinical and basic pharmacological research on erlotinib, sorafenib and sunitinib was carried out. Especially, in sunitinib therapy, we demonstrated that the breast cancer resistant protein in the intestine functions as a limiting factor for oral absorption, and that therapeutic drug monitoring could be helpful for avoiding severe toxicities, resulting in prolonged progression-free survival. 3) We quantitatively assessed side effect management by pharmacist intervention for outpatient chemotherapy. We calculated the improvement ratio between before and after pharmacist intervention, and found that 135 suggestions (50.8%) led to significant improvements, indicating that pharmacist intervention could be useful for attenuating the side effects of cancer chemotherapies.