Influence of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib: A Randomized Crossover Pharmacokinetic Study.

Regorafenib exposure could potentially be influenced by an interaction with acid-reducing drugs. In this crossover trial, patients were randomized into two sequence groups consisting of three phases: regorafenib intake alone, regorafenib with concomitant esomeprazole, and regorafenib with esomeprazole 3 hours prior. The primary end point was the relative difference (RD) in geometric means for regorafenib 0-24-hour area under the concentration-time curve (AUC0-24h ) and was analyzed by a linear mixed model in 14 patients. AUC0-24h for regorafenib alone was 55.9 µg·hour/mL (coefficient of variance (CV): 40%), and for regorafenib with concomitant esomeprazole or with esomeprazole 3 hours prior AUC0-24h was 53.7 µg·hour/mL (CV: 34%) and 53.6 µg·hour/mL (CV: 43%), respectively. No significant differences were identified when regorafenib alone was compared with regorafenib with concomitant esomeprazole (RD: -3.9%; 95% confidence interval (CI): -20.5 to 16.1%; P = 1.0) or regorafenib with esomeprazole 3 hours prior (RD: -4.1%; 95% CI: -22.8 to 19.2%; P = 1.0). These findings indicate that regorafenib and esomeprazole can be safely combined in clinical practice.

[Fatal pulmonary tumour embolism as initial manifestation of an occult coecum tumour]. / Fatale pulmonale tumorembolie als eerste manifestatie van een occulte coecumtumor.

A 57-year-old woman without significant medical history presented. She had suffered from dyspnoea for the past 2 days and persistent spasmodic abdominal complaints for the past 2 weeks. Physical examination revealed tachypnoea, tachycardia and slight abdominal tenderness. Laboratory investigations revealed hypoxaemia and a strongly elevated D-dimer level. Thorax radiography revealed no abnormalities and no indications for pulmonary embolism were revealed by the CT. Abdominal ultrasound revealed multiple enlarged lymph nodes. Shortly after admission and despite resuscitation the patient died. Autopsy revealed massive pulmonary tumour embolism that originated from a primary lymphogenic metastasized coecum carcinoma. Pulmonary tumour embolism is characterised by tumour cells in the pulmonary vascular system, which exhibit no continuity with parenchymal metastases. Due to the less than specific findings revealed by history taking, physical examination and additional tests, the condition is rarely diagnosed ante mortem.