Selinexor population pharmacokinetic and exposure–response analyses to support dose optimization in patients with diffuse large B-cell lymphoma
| Autor: | Hanbin Li, Russ Wada, Justin C Bader, Sharon Shacham, Shijie Tang, Jatin P. Shah, Hongmei Xu |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Oncology Cancer Research medicine.medical_specialty Adolescent Population Cmax Toxicology Young Adult 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) Adverse effect education Aged Aged 80 and over Pharmacology Volume of distribution education.field_of_study business.industry Lymphoma Non-Hodgkin Clinical Studies as Topic Middle Aged Triazoles medicine.disease Lymphoma Regimen Hydrazines Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis Female Lymphoma Large B-Cell Diffuse business Diffuse large B-cell lymphoma |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 88:69-79 |
| ISSN: | 1432-0843 0344-5704 |
| Popis: | Characterize the population PK and exposure–response (ER) relationships of selinexor in patients with diffuse large B-cell lymphoma (DLBCL) (efficacy endpoints) or other non-Hodgkin’s lymphoma (NHL) patients (safety endpoints) to determine the optimal dose in patients with DLBCL. This work included patients from seven clinical studies, with 800 patients for PK, 175 patients for efficacy and 322 patients for safety analyses. Logistic regression models and Cox-regression models were used for binary and time-to-event endpoints, respectively. Model-based simulations were performed to justify dose based on balance between efficacy and safety outcome. Selinexor pharmacokinetics were well-described by a two-compartment model with body weight as a significant covariate on clearance and central volume of distribution and gender on clearance. Overall response rate (ORR) in patients with DLBCL increased with day 1 Cmax and decreased in patients with higher baseline tumor size (p |
| Databáze: | OpenAIRE |
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