Unintentional combining enzalutamide with a moderate CYP2C8 inhibitor in a patient with metastatic castration-resistant prostate cancer: a case report.

BACKGROUND: Enzalutamide, registered for the treatment of metastatic castration-resistant prostate cancer (mCRPC), is an inducer of multiple CYP-enzymes. Enzalutamide itself is mainly converted by CYP2C8 to the active metabolite N-desmethylenzalutamide (NDME). Due to a pharmacokinetic interaction, combining enzalutamide with a moderate CYP2C8 inhibitor might result in higher enzalutamide concentrations. Addressing this interaction is challenging since pharmacokinetic data are missing. CASE PRESENTATION: We present a case of a Caucasian male with mCRPC who was treated with enzalutamide and a moderate CYP2C8 inhibitor, clopidogrel, concomitantly. Plasma trough levels (Ctrough) of enzalutamide and its active metabolite N-desmethylenzalutamide (NDME) were determined and compared when treated with and without clopidogrel. The sum concentration of enzalutamide and NDME was not affected by coadministration of a moderate CYP2C8 inhibitor. Both treatments were well tolerated and no major side effect were observed. CONCLUSION: This case report shows that enzalutamide can be safely prescribed while cotreated with a moderate CYP2C8-inhibitor, without reducing the dose. More research is warranted to make a statement about the effect of enzalutamide on clopidogrel.

A non-interventional retrospective cohort study of the interaction between methotrexate and proton pump inhibitors or aspirin.

INTRODUCTION: Methotrexate (MTX) is an antifolate drug, which is frequently used in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular secretion, which could lead to MTX toxicity. However, the evidence of the clinical relevance of this drug-drug interaction is inconsistent. No previous studies into the effect of low dose aspirin on the elimination of MTX in high-dose therapy have been performed. Therefore, we evaluated the interaction between MTX and PPIs or aspirin. METHODS: We conducted a non-interventional retrospective cohort study in patients treated with high dose MTX (≥500mg/m2 or >1000mg), between 2009 and 2016 at the OLVG ("Onze Lieve Vrouwe Gasthuis, Oost") in Amsterdam, the Netherlands. Patients were included if MTX concentrations were determined at 24, 48 or 72hours after high dose MTX treatment. We categorised the cycles of high dose MTX therapy into delayed elimination or normal elimination. Differences in patient characteristics and MTX dosing regimen were compared between all groups by X2-test, Fisher's exact probability test or Mann-Whitney U-test. RESULTS: In total, 89 high dose MTX cycles were included. Delayed MTX elimination was observed in 27 (30.3%) cycles. Co-administration of a PPI was significantly more frequent in the delayed elimination group than in the normal elimination group (P<0.001). There was no statistical effect observed by co-administration of aspirin. CONCLUSION: The use of PPIs during high dose MTX treatment can lead to delayed MTX elimination. Discontinuation of PPIs during high dose MTX treatment is recommended. Co-administration of aspirin did not influence the elimination of MTX, but further research is needed.

[Overdenture prostheses on implants versus complete dentures]. / Overkappingsprothese op implantaten versus volledige prothese.

OBJECTIVE: To establish the treatment outcome of implant retained overdentures (IRD) versus complete dentures (CD) in which the outcome assessment focuses on the patient's subjective evaluation ('denture-satisfaction and chewing ability'). DESIGN: A multicenter randomized clinical trial (prospective). SETTING: The department of Oral Function and Prosthetic Dentistry of the University of Nijmegen, the department of Oral and Maxillofacial Surgery of the University Hospital Nijmegen and the department of Oral and Maxillofacial Surgery and Maxillofacial Prosthodontics of the University Hospital Groningen. METHODS: In this study 151 patients with severely resorbed mandibles participated, treatment had been assigned according to a balanced allocation method. Denture satisfaction and chewing ability were assessed using questionnaires before and 1 year after treatment. RESULTS: Before treatment all patients were dissatisfied with their mandibular denture and they could hardly chew tough or had food. One year after treatment the IRD-group was satisfied with their mandibular denture, whereas only one third of the CD-group was satisfied. With respect to the chewing ability the IRO-group scored significantly better than the CD-group (p < or = 0.0001). CONCLUSION: For patients with a severely resorbed mandible, overdentures retained by dental implants appear to provide a more satisfactory solution to their denture-related problems.

Patient satisfaction and chewing ability with implant-retained mandibular overdentures: a comparison with new complete dentures with or without preprosthetic surgery.

PURPOSE: The objective of this study was to compare denture satisfaction and chewing ability of edentulous patients treated with dental implant-retained overdentures or with full dentures with or without previous preprosthetic surgery. PATIENTS AND METHODS: This study was a controlled clinical trial. Thirty-eight men and 52 women participated in the study. The mean height of the anterior mandible was 21 mm (range, 16 to 25 mm), measured on a lateral cephalometric radiograph. The subjects were randomly assigned to the three treatment modalities. The main outcome measures were denture satisfaction and chewing ability, which were assessed using questionnaires focusing on denture-related complaints and the ability to chew different types of food, and an overall denture satisfaction score. RESULTS: Based on the baseline data from the "denture complaints" and "chewing ability" questionnaires, nine interpretable factors could be extracted. Two factors did not vary following treatment and were excluded from the outcome analysis. At the 1-year evaluation five of seven factors showed significantly better scores for the two surgical groups than for the control group. The same was found for the overall denture satisfaction rate. CONCLUSION: Overdentures retained by dental implants or complete dentures made after a vestibuloplasty and deepening of the floor of the mouth provide a more satisfactory solution for denture-related problems than complete dentures alone. For the scale "functional complaints lower denture," the overdenture group showed even a significantly better score than the preprosthetic surgery group.

Patient satisfaction with implant-retained mandibular overdentures. A comparison with new complete dentures not retained by implants--a multicentre randomized clinical trial.

OBJECTIVES: The aim of this study was to establish the treatment outcome of full denture treatment with or without implant support, in which the outcome assessment focuses on the patient's subjective evaluation ('denture-satisfaction'). DESIGN: A multicenter randomized clinical trial. SUBJECTS: Thirty-two men and 118 women (mean age 56 +/- 9, range 35-84 years) participated in the study. The mean height of the mandible was 13 +/- 2 mm, measured on a lateral cephalometric radiograph. The patients were randomly assigned to either a group treated with implant-retained mandibular overdentures and a new maxillary denture, or to a control group treated with a new set of complete dentures. MAIN OUTCOME MEASURES: Denture satisfaction was assessed using questionnaires focusing on denture-related complaints and 'a general satisfaction rate'. RESULTS: Based on the baseline data, from the 'denture complaints' questionnaire six interpretable factors could be extracted. One factor did not vary following treatment and was excluded from the outcome analysis. At the 1-year evaluation three out of five factors showed significantly better scores for the group treated with implants than for the control-group. The same was found for the general satisfaction rate. CONCLUSION: For patients with a severely resorbed mandible, overdentures retained by dental implants appear to provide a more satisfactory solution to their denture-related problems.