IntroductionMany patients experience unrelieved neuropathic cancer-related pain. Most current analgesic therapies have psychoactive side effects, lack efficacy data for this indication and have potential medication-related harms. The local anaesthetic lidocaine (lignocaine) has the potential to help manage neuropathic cancer-related pain when administered as an extended, continuous subcutaneous infusion. Data support lidocaine as a promising, safe agent in this setting, warranting further evaluation in robust, randomised controlled trials. This protocol describes the design of a pilot study to evaluate this intervention and explains the pharmacokinetic, efficacy and adverse effects evidence informing the design.Methods and analysisA mixed-methods pilot study will determine the feasibility of an international first, definitive phase III trial to evaluate the efficacy and safety of an extended continuous subcutaneous infusion of lidocaine for neuropathic cancer-related pain. This study will comprise: a phase II double-blind randomised controlled parallel-group pilot of subcutaneous infusion of lidocaine hydrochloride 10% w/v (3000 mg/30 mL) or placebo (sodium chloride 0.9%) over 72 hours for neuropathic cancer-related pain, a pharmacokinetic substudy and a qualitative substudy of patients’ and carers’ experiences. The pilot study will provide important safety data and help inform the methodology of a definitive trial, including testing proposed recruitment strategy, randomisation, outcome measures and patients’ acceptability of the methodology, as well as providing a signal of whether this area should be further investigated.Ethics and disseminationParticipant safety is paramount and standardised assessments for adverse effects are built into the trial protocol. Findings will be published in a peer-reviewed journal and presented at conferences. This study will be considered suitable to progress to a phase III study if there is a completion rate where the CI includes 80% and excludes 60%. The protocol and Patient Information and Consent Form have been approved by Sydney Local Health District (Concord) Human Research Ethics Committee 2019/ETH07984 and University of Technology Sydney ETH17-1820.Trial registration numberANZCTR ACTRN12617000747325.

ObjectivesTo describe the contemporary real-world use of cyclizine for nausea or vomiting, and the associated benefits and harms.MethodsThis was a prospective, consecutive case series of routine clinical use of cyclizine for nausea or vomiting in palliative care conducted across 19 sites in Australia, Aotearoa/New Zealand and the UK. Clinical outcomes were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline and 72 hours after initiation of cyclizine. Ad hoc safety reporting continued for 2 weeks.ResultsData were collected from 101 patients between May 2018 and December 2020. Cyclizine was mostly used in combination with another antiemetic. Overall, 79 patients benefited and 32 experienced harm (56 had benefit without harm; 9 had harm without benefit). The most common harms were constipation (13%), somnolence (9%) and confusion (7%), adding to the already high rates of these symptoms at baseline. For the four patients with serious harms (grade ≥3), these were exacerbations of existing symptoms. Nine patients stopped cyclizine at 72 hours and a further 20 patients within 2 weeks. The most common reasons for stopping were lack of benefit and symptom resolution; none stopped because of harms.ConclusionsWhen used as described in a palliative care setting, cyclizine benefits about three-quarters of patients, with about one-third experiencing tolerable harms.

In Chronic Obstructive Pulmonary Disease (COPD), expiratory flow limitation and gas trapping cause an increase in FRC, known as hyperinflation. Hyperinflation impedes diaphragm function, causes breathlessness and reduces exercise capacity. In healthy people, elastic chest compression reduced FRC. Therefore, we investigated whether elastic chest compression could reduce hyperinflation in patients with COPD. METHODS: Eight patients with COPD and gas trapping (RV > 120% predicted) performed body plethysmography at baseline and with elastic chest compression placed at the Xiphisternum and over the abdomen. Participants then underwent two magnetic resonance imaging scans of the thorax without and with elastic chest compression to measure the height, length and angle of the diaphragm at FRC. Data are presented as mean ± SD. RESULTS: COPD participants were 66±7.9 years old with moderate to severe airflow obstruction (FEV 1 = 48.2±19% predicted). Elastic chest compression reduced FRC (148.7±25 vs 138.9±22% predicted, p = 0.002) but did not alter TLC or RV (p = 0.25 and 0.58, respectively). This led to an increase in inspiratory capacity with elastic chest compression of 0.22±0.24L (2.35±0.85 vs 2.57±0.92L, p = 0.04). This was accompanied by an increase in the height and length of the diaphragm as well as a decrease in the angle of the diaphragm (p < 0.01 for all). CONCLUSION: In patients with COPD, elastic chest compression reduced hyperinflation and improved the curvature of the diaphragm. This suggests that an elastic chest compression may be a novel strategy in patients with COPD to improve breathing mechanics, and hence breathlessness and exercise capacity.