Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors.

BACKGROUND: GSK3368715, a first-in-class, reversible inhibitor of type I protein methyltransferases (PRMTs) demonstrated anticancer activity in preclinical studies. This Phase 1 study (NCT03666988) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK3368715 in adults with advanced-stage solid tumors. METHODS: In part 1, escalating doses of oral once-daily GSK3368715 (50, 100, and 200 mg) were evaluated. Enrollment was paused at 200 mg following a higher-than-expected incidence of thromboembolic events (TEEs) among the first 19 participants, resuming under a protocol amendment starting at 100 mg. Part 2 (to evaluate preliminary efficacy) was not initiated. RESULTS: Dose-limiting toxicities were reported in 3/12 (25%) patients at 200 mg. Nine of 31 (29%) patients across dose groups experienced 12 TEEs (8 grade 3 events and 1 grade 5 pulmonary embolism). Best response achieved was stable disease, occurring in 9/31 (29%) patients. Following single and repeat dosing, GSK3368715 maximum plasma concentration was reached within 1 h post dosing. Target engagement was observed in the blood, but was modest and variable in tumor biopsies at 100 mg. CONCLUSION: Based on higher-than-expected incidence of TEEs, limited target engagement at lower doses, and lack of observed clinical efficacy, a risk/benefit analysis led to early study termination. TRIAL REGISTRATION NUMBER: NCT03666988.

Current training provision and training needs in oral health for UK general practice trainees: survey of General Practitioner Training Programme Directors.

BACKGROUND: In the UK the incidence of oral cancers has risen by a third in the last decade, and there have been minimal improvements in survival rates. Moreover, a significant proportion of the population no longer access dental health services regularly, instead presenting their oral health concerns to their General Medical Practitioner. Therefore, General Practitioners (GP) have an important role in the diagnosis of oral health pathologies and the earlier detection of oral cancers. This study aims to understand the current provision of training in oral health and cancer for GP trainees and to identify how unmet training needs could be met. METHODS: A cross-sectional survey of GP Training Programme Directors using an online questionnaire asking about current oral health education training (hospital placements and structured teaching), the competencies covered with trainees and ways to improve oral health training. Quantitative data were analysed using descriptive statistics and content analysis was undertaken of free text responses. RESULTS: We obtained responses from 132 GP Training Programme Directors (GPTPDs), from 13 of the 16 UK medical deaneries surveyed. The majority of respondents (71.2%) indicated that their programmes did not provide any structured oral health training to GP trainees and that ≤ 10% of their trainees were undertaking hospital posts relevant to oral health. GPTPDs were of the view that the quality of oral health training was poor, relative to the specified competencies, and that teaching on clinical presentations of 'normal' oral anatomy was particularly poor. It was envisaged that oral health training could be improved by access to specialist tutors, e-learning programmes and problem-based-learning sessions. Respondents highlighted the need for training sessions to be relevant to GPs. Barriers to improving training in oral health were time constraints, competing priorities and reluctance to taking on the workload of dentists. CONCLUSIONS: This UK-wide survey has identified important gaps in the training of GP trainees in relation to oral health care and cancer detection. Addressing these knowledge and skill gaps, particularly in the identification of oral cancers, will help to improve oral health and, more importantly, the timely diagnosis of oral cancer.

Leiomyosarcoma of the tongue: a case report.

Primary leiomyosarcomas arising from within the tongue are extremely rare. Only eight cases have been previously reported on Medline to our knowledge. We describe a case of a 46-year-old woman who presented with a lesion rapidly increasing in size on the lateral aspect of her tongue, which was excised. We present a completed-5-year follow-up.