Tokophobia and fear of birth: a workshop consensus statement on current issues and recommendations for future research.

Objective: To discuss and develop a statement on the current state of the evidence and opinion in Fear of Childbirth (FoC) and Tokophobia (Tocophobia), and to provide recommendations. Background: A group met in 2019 to discuss the state of clinical and academic knowledge relating to FoC/Tokophobia. Five key areas were agreed as the focus of the meeting. Methods: 12 internationally acknowledged experts, in this or a closely related area (e.g. PTSD) met to discuss their understanding of the evidence for FoC/ Tokophobia and current practice. The consensus described in this paper constitutes the expression of the general opinion of the participants and does not necessarily imply unanimity. Keys points: Work focussed on tokophobia is recent and there remains a wide range of issues, which were addressed in the workshop including complexity in defining prevalence, a theoretical lack of understanding, which creates challenge for robust assessment and the identification of risk factors. An improved aetiological and developmental understanding of the tokophobia is required to underpin appropriate, effective and evidence-based interventions. Evaluation of pathways of care and relevant interventions, should be a focus of future research. Conclusion: Significant gaps remain within the FoC/tokophobia knowledge base. Further research is necessary.

Effects of lapatinib monotherapy: results of a randomised phase II study in therapy-naive patients with locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Lapatinib is a dual inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER-2) tyrosine kinases. This study investigated the pharmacodynamic and clinical effects of lapatinib in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: In total, 107 therapy-naive patients with locally advanced SCCHN were randomised (2 : 1) to receive lapatinib or placebo for 2-6 weeks before chemoradiation therapy (CRT). Endpoints included apoptosis and proliferation rates, clinical response, and toxicity. RESULTS: Versus placebo, lapatinib monotherapy did not significantly increase apoptosis detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labelling or caspase-3 assays. A statistically significant decrease in proliferation using Ki67 assay was observed (P=0.030). In a subset of 40 patients that received 4 weeks of lapatinib or placebo, objective response rate (ORR) was 17% (n=4/24) vs 0% (n=0/16). In the lapatinib single-agent responders, all had EGFR overexpression, 50% had EGFR amplification, and 50% had HER2 expression by immunohistochemistry (including one patient with HER2 amplification). However, these patients showed variable modulation of apoptosis, proliferation, and phosphorylated EGFR on drug treatment. Following CRT, there was a statistically non-significant difference in ORR between lapatinib (70%) and placebo (53%). There was no clear correlation between changes in apoptosis or proliferation and response to chemoradiation. Mucosal inflammation, asthenia, odynophagia, and dysphagia were the most commonly reported adverse events with lapatinib. CONCLUSION: Short-term lapatinib monotherapy did not demonstrate apoptotic changes, but provided evidence of clinical activity in locally advanced SCCHN, and warrants further investigation in this disease.