Pharmacodynamic analysis of eribulin safety in breast cancer patients using real‐world postmarketing surveillance data
| Autor: | Valentina Fermanelli, Yusuke Tanigawara, Yukinori Sakata, Hidefumi Kasai, Toshiaki Takahashi, Toshiyuki Matsuoka, Mika Ishii, Takahisa Kawamura |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Oncology Cancer Research medicine.medical_specialty Postmarketing surveillance Breast Neoplasms Neutropenia 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Breast cancer Elimination rate constant Clinical Research Internal medicine Product Surveillance Postmarketing medicine Humans neutropenia Computer Simulation postmarketing surveillance 030212 general & internal medicine Furans eribulin Serum Albumin Aged Aged 80 and over business.industry Original Articles General Medicine Ketones Middle Aged medicine.disease Metastatic breast cancer pharmacodynamic chemistry 030220 oncology & carcinogenesis Pharmacodynamics Absolute neutrophil count Female Original Article Neoplasm Recurrence Local business pharmacometric Eribulin |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | Postmarketing surveillance is useful to collect safety data in real‐world clinical settings. In this study, we applied postmarketing real‐world data on a mechanistic model analysis for neutropenic profiles of eribulin in patients with recurrent or metastatic breast cancer. Demographic and safety data were collected using an active surveillance method from eribulin‐treated recurrent or metastatic breast cancer patients. Changes in neutrophil counts over time were analyzed using a mechanistic pharmacodynamic model. Pathophysiological factors that might affect the severity of neutropenia were investigated, and neutropenic patterns were simulated for different treatment schedules. Clinical and laboratory data were collected from 401 patients (5199 neutrophil count measurements) who had not received granulocyte colony‐stimulating factor and were eligible for pharmacodynamic analysis. The estimated mean parameters were as follows: mean transit time = 104.5 h, neutrophil proliferation rate constant = 0.0377 h−1, neutrophil elimination rate constant = 0.0295 h−1, and linear coefficient of drug effect = 0.0413 mL/ng. Low serum albumin levels and low baseline neutrophil counts were associated with severe neutropenia. The probability of grade ≥3 neutropenia was predicted to be 69%, 27%, and 27% for patients on standard, biweekly, and triweekly treatment scenarios, respectively, based on virtual simulations using the developed pharmacodynamic model. In conclusion, this is the first application of postmarketing surveillance data to a model‐based safety analysis. This analysis of safety data reflecting authentic clinical settings will provide useful information on the safe use and potential risk factors of eribulin. |
| Databáze: | OpenAIRE |
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