Fanny Leenhardt1,2,3,4, Marie Alexandre5, Severine Guiu6,5, Stephane Pouderoux5, Melanie Beaujouin7, Gerald Lossaint8, Laurent Philibert9, Alexandre Evrard10,6,11, William Jacot6,5. 1. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France. fanny.leenhardt@icm.unicancer.fr. 2. Service Pharmacie, Institut du Cancer de Montpellier, Université de Montpellier, 208 rue des Apothicaires, 34298, Montpellier, France. fanny.leenhardt@icm.unicancer.fr. 3. Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Montpellier, France. fanny.leenhardt@icm.unicancer.fr. 4. Institut du Cancer de Montpellier, 208 Avenue des Apothicaires, Montpellier, France. fanny.leenhardt@icm.unicancer.fr. 5. Département d'oncologie Médicale, Institut du Cancer de Montpellier, Université de Montpellier, 208 rue des Apothicaires, 34298, Montpellier, France. 6. Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Montpellier, France. 7. Centre de Recherche Clinique, Institut du Cancer de Montpellier, 208 rue des Apothicaires, 34298, Montpellier, France. 8. Département de Recherche Clinique, Institut du Cancer de Montpellier, Université de Montpellier, 208 rue des Apothicaires, 34298, Montpellier, France. 9. Service Pharmacie, Institut du Cancer de Montpellier, Université de Montpellier, 208 rue des Apothicaires, 34298, Montpellier, France. 10. Laboratoire de Pharmacocinétique, Faculté de Pharmacie, Université de Montpellier, Montpellier, France. 11. Laboratoire de Biochimie et Biologie Moléculaire, Centre Hospitalier Universitaire Nîmes, Nîmes, France.
Abstract
PURPOSE: Pharmacist consultation is unfrequently performed in oncology clinical trials that include patients who often have many co-treatments increasing the risk of drug-drug interactions (DDI). The aim of this study was to determine whether best possible medication history (BPMH) by hospital pharmacist at inclusion and therapeutic drug monitoring could be used for DDI risk evaluation and for current oral targeted therapy management. METHODS: A prospective clinical trial (ALCINA 2, NCT04025541) was carried out in metastatic breast cancer cohort treated by palbociclib to conduct pharmacokinetics-toxicity correlation study. BPMH was prospectively performed by the hospital pharmacist at each trial inclusion, followed by a contact to the patient's community pharmacy to complete the collected data. Pharmacokinetic analysis was performed on blood samples collected at day 15 of cycle 1 of palbociclib treatment. RESULTS: Pharmacist interventions indicated that at inclusion, current medications were incomplete for 63% of the enrolled patients (32/51). It allowed the real-time management of high-risk DDI detected in third of patients. The palbociclib Ctrough geometric median (min-max) was significantly higher in cohort with potential DDI [106 ng/mL (66.7-113)], than cohort without potential DDI [70.1 ng/mL (54.1-89.7)], p = 0.0284. CONCLUSION: This is the first prospective study evaluating the relevance of proactive BPMH by pharmacist with contact to the community pharmacy during the inclusion step of a clinical trial to ensure the efficacy and safety of the investigated drug. This investigation was thus able to highlight the statistically significant impact of these DDI on palbociclib plasma concentration variation during the clinical trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04025541.
PURPOSE: Pharmacist consultation is unfrequently performed in oncology clinical trials that include patients who often have many co-treatments increasing the risk of drug-drug interactions (DDI). The aim of this study was to determine whether best possible medication history (BPMH) by hospital pharmacist at inclusion and therapeutic drug monitoring could be used for DDI risk evaluation and for current oral targeted therapy management. METHODS: A prospective clinical trial (ALCINA 2, NCT04025541) was carried out in metastatic breast cancer cohort treated by palbociclib to conduct pharmacokinetics-toxicity correlation study. BPMH was prospectively performed by the hospital pharmacist at each trial inclusion, followed by a contact to the patient's community pharmacy to complete the collected data. Pharmacokinetic analysis was performed on blood samples collected at day 15 of cycle 1 of palbociclib treatment. RESULTS: Pharmacist interventions indicated that at inclusion, current medications were incomplete for 63% of the enrolled patients (32/51). It allowed the real-time management of high-risk DDI detected in third of patients. The palbociclib Ctrough geometric median (min-max) was significantly higher in cohort with potential DDI [106 ng/mL (66.7-113)], than cohort without potential DDI [70.1 ng/mL (54.1-89.7)], p = 0.0284. CONCLUSION: This is the first prospective study evaluating the relevance of proactive BPMH by pharmacist with contact to the community pharmacy during the inclusion step of a clinical trial to ensure the efficacy and safety of the investigated drug. This investigation was thus able to highlight the statistically significant impact of these DDI on palbociclib plasma concentration variation during the clinical trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT04025541.
Authors: Wan Sun; Karen J Klamerus; Lisa M Yuhas; Sylvester Pawlak; Anna Plotka; Melissa O'Gorman; Leonid Kirkovsky; Maha Kosa; Diane Wang Journal: Clin Pharmacol Drug Dev Date: 2017-04-21
Authors: Rossana Roncato; Lorenzo Gerratana; Lorenza Palmero; Sara Gagno; Ariana Soledad Poetto; Elena Peruzzi; Martina Zanchetta; Bianca Posocco; Elena De Mattia; Giovanni Canil; Martina Alberti; Marco Orleni; Giuseppe Toffoli; Fabio Puglisi; Erika Cecchin Journal: Front Pharmacol Date: 2022-07-22 Impact factor: 5.988