Pimasertib, a selective oral MEK1/2 inhibitor: absolute bioavailability, mass balance, elimination route, and metabolite profile in cancer patients.

AIM: This trial (NCT: 01713036) investigated the absolute bioavailability, mass balance and metabolite profile of pimasertib in a new design combining these investigations in a single group of patients. METHODS: Six male patients with pathologically confirmed, locally advanced or metastatic solid tumours were enrolled. Exclusion criteria included Eastern Cooperative Oncology Group performance status >1. In Part A of the trial, patients received a 60 mg oral dose of unlabelled pimasertib followed by an intravenous (i.v.) tracer dose of [14 C]pimasertib 2 µg (equalling 9 kBq) as a bolus injection, one hour after the oral dose, on Day 1. On Day 8, all patients received 60 mg pimasertib capsules spiked with 2.6 MBq of [14 C]pimasertib. Patients received 60 mg oral unlabelled pimasertib twice daily from Day 3 to Day 21 of Part A and in subsequent 21-day cycles in Part B. RESULTS: Following i.v. administration, [14 C]pimasertib exhibited a geometric mean total body clearance of 45.7 l h-1 (geometric coefficient of variation [geometric CV]: 47.2%) and a volume of distribution of 229 l (geometric CV: 42.0%). Absolute bioavailability was 73%. The majority of the oral [14 C] dose (85.1%) was recovered in excreta. Total radioactivity was mainly excreted into urine (52.8%) and faeces (30.7%) with 78.9% of the [14 C] dose recovered as metabolites. Two major circulating metabolites were identified in plasma: a carboxylic acid (M445) and a phosphoethanolamine conjugate (M554). The safety profile was in line with the published pimasertib trials. CONCLUSION: Pimasertib showed a favourable pharmacokinetic profile with high absolute bioavailability and a unique metabolic pathway (conjugation with phosphoethanolamine).

[Detection of recurrent head and neck cancer with positron emission tomography]. / Fej-nyaki tumorok daganatkiújulásának megítélése pozitronemissziós tomográfia alkalmazásával.

Differentiation between recurrence and post-therapeutic lesions in patients with previously treated head and neck cancer can be a real diagnostic problem. The authors discuss the role of positron emission tomography in restaging of this disease by a retrospective analysis based on 20 scans of 17 patients. PET findings were correct in identifying tumors in 85% of patients (11/13) in the group of positive PET results. All negative PET findings (4/4) were also correct during the follow-up. PET results were validated in 88% (15/17) of the patients. In one case silent distant metastases were also detected. PET is a reliable method in restaging previously treated head and neck cancer patients as it can differentiate post-therapeutic changes from tumor relapse.

[Platysma myocutaneous island flap reconstruction after excision of a tongue-tongue base tumor]. / Platysma myocutan lebeny-rekonstrukció nyelv-nyelvgyöki daganat mútéte után.

The authors' aim was to introduce a simple, safe and reliable method for reconstruction of soft tissue defects after excision of carcinomas of the tongue, tongue base and posterior part of the floor of the mouth. The musculocutaneous flaps are options of larger soft tissue defects in the maxillofacial area. After excision of a tongue-tongue base tumour with mandibular splitting method a platysma myocutaneous flap was applied for reconstruction. The flap was taken from an appropriate place convenient to functional acceptions and was adapted anatomically into the defect. The result was that the patient healed primarily with undisturbed blood circulation of the flap. The functional rehabilitation period was short, the flap tolerated the irradiation. The authors observed that the use of the platysma island flap can be an option for reconstruction of defects after ablative surgery on the tongue-tongue base. This simple method worked reliable even after intra-arterial cytostatic treatment. The acceptable functional result depends on the placement of the island flap on the neck flap prepared for neck dissection.