Reducing the time before consulting with symptoms of lung cancer:a randomised controlled trial in primary care

Background: Most individuals with lung cancer have symptoms for several months before presenting to their GP. Earlier consulting may improve survival. Aim: To evaluate whether a theory-based primary care intervention increased timely consulting of individuals with symptoms of lung cancer. Design and setting: Open randomised controlled trial comparing intervention with usual care in two general practices in north-east Scotland. Method: Smokers and ex-smokers aged ≥55 years were randomised to receive a behavioural intervention or usual care. The intervention comprised a single nurse consultation at participants' general practice and a self-help manual. The main outcomes were consultations within target times for individuals with new chest symptoms (≤3 days haemoptysis, ≤3 weeks other symptoms) in the year after the intervention commenced, and intentions about consulting with chest symptoms at 1 and 6 months. Results: Two hundred and twelve participants were randomised and 206 completed the trial. The consultation rate for new chest symptoms in the intervention group was 1.19 (95% confidence interval [CI] = 0.92 to 1.53; P = 0.18) times higher than in the usual-care group and the proportion of consultations within the target time was 1.11 (95% CI = 0.41 to 3.03; P = 0.83) times higher. One month after the intervention commenced, the intervention group reported intending to consult with chest symptoms 31 days (95% CI = 7 to 54; P = 0.012) earlier than the usual care group, and at 6 months this was 25 days (95% CI = 1.5 to 48; P = 0.037) earlier. Conclusion: Behavioural intervention in primary care shortened the time individuals at high risk of lung disease intended to take before consulting with new chest symptoms (the secondary outcome of the study), but increases in consultation rates and the proportions of consultations within target times were not statistically significant. © British Journal of General Practice.

Developing a complex intervention to reduce time to presentation with symptoms of lung cancer

Background - Lung cancer is the commonest cause of cancer in Scotland and is usually advanced at diagnosis. Median time between symptom onset and consultation is 14 weeks, so an intervention to prompt earlier presentation could support earlier diagnosis and enable curative treatment in more cases. Aim - To develop and optimise an intervention to reduce the time between onset and first consultation with symptoms that might indicate lung cancer. Design and setting - Iterative development of complex healthcare intervention according to the MRC Framework conducted in Northeast Scotland. Method - The study produced a complex intervention to promote early presentation of lung cancer symptoms. An expert multidisciplinary group developed the first draft of the intervention based on theory and existing evidence. This was refined following focus groups with health professionals and high-risk patients. Results - First draft intervention components included: information communicated persuasively, demonstrations of early consultation and its benefits, behaviour change techniques, and involvement of spouses/partners. Focus groups identified patient engagement, achieving behavioural change, and conflict at the patient–general practice interface as challenges and measures were incorporated to tackle these. Final intervention delivery included a detailed self-help manual and extended consultation with a trained research nurse at which specific action plans were devised. Conclusion -The study has developed an intervention that appeals to patients and health professionals and has theoretical potential for benefit. Now it requires evaluation.

Double-blind, placebo-controlled, randomized study of eicosapentaenoic acid diester in patients with cancer cachexia

Purpose: Eicosapentaenoic acid (EPA) has been proposed to have specific anticachectic effects. This trial compared EPA diethyl ester with placebo in cachectic cancer patients for effects on weight and lean body mass. Patients and Methods: Five hundred eighteen weight-losing patients with advanced gastrointestinal or lung cancer were studied in a multicenter, double-blind, placebo controlled trial. Patients were randomly assigned to receive a novel preparation of pure EPA at a dose of 2 g or 4 g daily or placebo (2g EPA, n = 175; 4 g EPA, n = 172; placebo, n = 171). Patients were assessed at 4 weeks and 8 weeks. Results: The groups were well balanced at baseline. Mean weight loss at baseline was 18% (n = 518). Over the 8-week treatment period, both intention-to-treat analysis and per protocol analysis revealed no statistically significant improvements in survival, weight, or other nutritional variables. There was, however, a trend in favor of EPA with analysis of the primary end point, weight, at 8 weeks showing a borderline, nonsignificant treatment effect (P = .066). Relative to placebo, mean weight increased by 1.2 kg with 2 g EPA (95% CI, 0 kg to 2.3 kg) and by 0.3 kg with 4g EPA (-0.9 kg to 1.5 kg). Conclusion: The results indicate no statistically significant benefit from single agent EPA in the treatment of cancer cachexia. Future studies should concentrate on other agents or combination regimens. © 2006 by American Society of Clinical Oncology.

Synthesis and biological evaluation of potential anti-cancer agents

The new technology of combinational chemistry has been introduced to pharmaceutical companies, improving and making more efficient the process of drug discovery. Automated combinatorial chemistry in the solution-phase has been used to prepare a large number of compounds of anti-cancer screening. A library of caffeic acid derivatives has been prepared by the Knoevenagel condensation of aldehyde and active methylene reagents. These products have been screened against two murine adenocarcinoma cell lines (MAC) which are generally refractive to standard cytotoxic agents. The target of anti-proliferative action was the 12- and 15-lipoxygenase enzymes upon which these tumour cell lines have been shown to be dependent for proliferation and metastasis. Compounds were compared to a standard lipoxygenase inhibitor and if found to be active anti-proliferative agents were tested for their general cytotoxicity and lipoxygenase inhibition. A solid-phase bound catalyst, piperazinomethyl polystyrene, was devised and prepared for the improved generation of Knoevenagel condensation products. This piperazinomethyl polystyrene was compared to the traditional liquid catalyst, piperidine, and was found to reduce the amount of by-products formed during reaction and had the advantage of easy removal from the reaction. 13C NMR has been used to determine the E/Z stereochemistry of Knoevenagel condensation products. Soluble polymers have been prepared containing different building blocks pendant to the polymer backbone. Aldehyde building blocks incorporated into the polymer structure have been subjected to the Knoevenagel condensation. Cleavage of the resultant pendant molecules has proved that soluble linear polymers have the potential to generate combinatorial mixtures of known composition for biological testing. Novel catechol derivatives have been prepared by traditional solution-phase chemistry with the intention of transferring their synthesis to a solid-phase support. Catechol derivatives prepared were found to be active inhibitors of lipoxygenase. Soluble linear supports for the preparation of these active compounds were designed and tested. The aim was to develop a support suitable for the automated synthesis of libraries of catechol derivatives for biological screening.