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This is the first randomised study to evaluate toxicity and survival outcomes of two neoadjuvant chemoradiotherapy (CRT) regimens for patients with localised oesophageal adenocarcinoma (OAC) or gastro-oesophageal junction (GOJ) adenocarcinoma. The initial results showed comparable toxicity between regimens and pathological complete response (pCR) rate favouring CarPacRT. Herein, we report survival, progression patterns, and long-term toxicity after a median follow-up of 40.7 months. NeoSCOPE was an open-label, UK multicentre, randomised, phase II trial. Eighty-five patients with resectable OAC or GOJ adenocarcinoma, ≥cT3 and/or ≥cN1 (TNM v7), suitable for neoadjuvant CRT, were recruited between October 2013 and February 2015. Patients were randomised to OxCapRT (oxaliplatin 85 mg/m2 on Days 1, 15, and 29; capecitabine 625 mg/m2 orally twice daily on days of radiotherapy [RT]) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m2 on Days 1, 8, 15, 22, and 29). RT dose was 45 Gy/25 fractions/5 weeks. Both arms received induction chemotherapy (two cycles oxaliplatin 130 mg/m2 on Day 1, capecitabine 625 mg/m2 orally twice daily on Days 1–21) before CRT. Surgery was performed 6–8 weeks after CRT. The primary end-point was pCR. Secondary end-points were toxicity, progression-free survival (PFS), overall survival (OS), and patterns of progression. Eighty-five patients were recruited from 17 UK centres. The median OS was 41.7 months (95% confidence interval [CI] 19.6 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable hazard ratio [HR] = 0.48, 95% CIs: 0.24–0.95, P = 0.035). The median PFS was 32.6 months (95% CIs: 17.1 to not reached) in the OxCapRT arm and was not reached in the CarPacRT arm (multivariable HR = 0.54, 95% CIs: 0.29–1.01, P = 0.053). In both arms, the distant progression was twice as common as locoregional progression. OS and PFS favoured neoadjuvant CarPacRT over OxCapRT. Distant was more common than locoregional progression; therefore, priority should be given to optimising the systemic treatment component. EudraCT Number: 2012-000640-10; ClinicalTrials.gov: NCT01843829. • Randomised study of neoadjuvant chemoradiotherapy for oesophageal adenocarcinoma. • The median overall survival was significantly better with CarPacRT. • Across both arms, the distant was more common than locoregional progression. [ABSTRACT FROM AUTHOR]

Concurrent chemoradiotherapy is the standard treatment for anal cancer. Following national UK implementation of intensity-modulated radiotherapy (IMRT), this prospective, national cohort evaluates the one-year oncological outcomes and patient-reported toxicity outcomes (PRO) after treatment. A national cohort of UK cancer centers implementing IMRT was carried out between February to July 2015. Cancer centers provided data on oncological outcomes, including survival, and disease and colostomy status at one-year. EORTC-QLQ core (C30) and colorectal (CR29) questionnaires were completed at baseline and one-year followup. The PRO scores at baseline and one year were compared. 40 UK Cancer Centers returned data with a total of 187 patients included in the analysis. 92% received mitomycin with 5-fluorouracil or capecitabine. One-year overall survival was 94%; 84% were disease-free and 86% colostomy-free at one-year followup. At one year, PRO results found significant improvements in buttock pain, blood and mucus in stools, pain, constipation, appetite loss, and health anxiety compared to baseline. No significant deteriorations were reported in diarrhea, bowel frequency, and flatulence. Urinary symptom scores were low at one year. Moderate impotence symptoms at baseline remained at one year, and a moderate deterioration in dyspareunia reported. With national anal cancer IMRT implementation, at this early pre-defined time point, one-year oncological outcomes were reassuring and resulted in good disease-related symptom control. one-year symptomatic complications following CRT for anal cancer using IMRT techniques appear to be relatively mild. These PRO results provide a basis to benchmark future studies. • Significant improvements in pain, blood in stool and health anxiety at one-year. • No significant deterioration in bowel or urinary symptoms. • Moderate male and female sexual dysfunction reported. • 94% one-year overall survival in a national cohort following anal cancer (chemo)IMRT. [ABSTRACT FROM AUTHOR]

Introduction: Fluoropyrimidines (5-fluorouracil and capecitabine) are used in the treatment of various cancers. The enzyme dihydropyrimidine dehydrogenase (DPD) plays a key role in their metabolism (Lunenburg 2020). Some patients have reduced DPD activity leading to an increased risk of severe/fatal toxicity (Amstutz et al., 2017). In March 2020, the EMA Pharmacovigilance Risk Assessment Committee recommended DPD deficiency testing prior to starting fluoropyrimidines (UK Chemotherapy Board, 2020). Testing for DPD was introduced at Mount Vernon in March 2021. Aims and objectives: To review if DPD testing meets the standards set by the UKCB and as agreed with the consultant team. To ascertain if: All patients starting fluoropyrimidines are being tested for DPD prior to treatment. All patients being tested for DPD have no delays in treatment. Method: Data was collected retrospectively over 10 months from March 2021 to December 2021. Information from blood test reports, ChemoCare and patient notes were obtained. Results: 348 patients were initiated on fluoropyrimidinebased therapy. Compliance with audit standards is summarised in table 1. 4.7% (n = 15) of patients did not have a DPD test, with reasons unknown. The turnaround time for DPD results varied each month but averaged at 10 days. For some patients, this caused a delay in starting treatment whereas others were delayed due to the DPD test not being ordered on time, chair capacity, and other reasons. Obtaining results from different pathology systems (i.e. Guy’s and St Thomas’, North West London, Watford General, and Royal Marsden) also led to delays. Discussion: This analysis shows that > 95% of patients are being routinely tested for DPD however testing pathway delays are having an impact on patients starting treatment. Overall, 40% of the standards are being adhered to (standards 3 and 4); however, some standards have not been achieved (standards 1, 2 and 5). Recommendation: Create a centralised portal system for which all DPD results are reported and accessible. Due to multiple laboratory sites where DPD testing is conducted, there is difficulty in chasing available results, consequently leading to delays in treatment. Having a central reporting system could also save costs as it prevents patients being re-tested. Interface DPD results into electronic prescribing systems to ensure no prescribing errors. Currently, the results are being manually typed by clinicians onto ChemoCare. Integrated reporting will ensure appropriate patient flow and prevent human errors and delays in treatment. Further investigation on the impact DPD testing has had on reducing fluoropyrimidine toxicity. Present the results of this audit at doctor’s educational meetings and to nursing and pharmacy staff (delivered by the educational lead pharmacist). A collaborative approach can help improve strategies for DPD testing. Re-audit by the end of 2022 to ensure that improvements are sustained after the above recommendations have been implemented. Conclusion: DPD testing is a novel approach to preventing fluoropryimidine toxicity. This audit revealed that not all national standards are being adhered to; consequently leading to treatment delays. However, effective training and a centralised system should increase compliance with the standards set by the UKCB and as agreed with the consultant team. [ABSTRACT FROM AUTHOR]

Background Platinum-based combination chemotherapy is standard treatment for the majority of patients with advanced non-small-cell lung cancer (NSCLC). The trial investigates the importance of the choice of platinum agent and dose of cisplatin in relation to patient outcomes. Methods The three-arm randomised phase III trial assigned patients with chemo-naïve stage IIIB/IV NSCLC in a 1:1:1 ratio to receive gemcitabine 1250 mg/m 2 on days 1 and 8 of a 3-week cycle with cisplatin 80 mg/m 2 (GC80) or cisplatin 50 mg/m 2 (GC50) or carboplatin AUC6 (GCb6) for a maximum of four cycles. Primary outcome measure was survival time, aiming to test for a difference between treatment arms and also assess non-inferiority with pre-defined margin selected as hazard ratio (HR) of 1.2. Secondary outcome measures included response rate, adverse events and quality of life (QoL). Findings The trial recruited 1363 patients. Survival time differed significantly across the three treatment arms (p = 0.046) with GC50 worst with median 8.2 months compared to 9.5 for GC80 and 10.0 for GCb6. HRs (adjusted) for GC50 compared to GC80 was 1.13 (95% confidence interval [CI] 0.99–1.29) and for GC50 compared to GCb6 was 1.23 (95% CI: 1.08–1.41). GCb6 was significantly non-inferior to GC80 (HR = 0.93, upper limit of one-sided 95% CI 1.04). Adjusting for QoL did not change the findings. Best objective response rates were 29% (GC80), 20% (GC50) and 27% (GCb6), p < 0.007. There were more dose reductions and treatment delays in the GCb6 arm and more adverse events (60% with at least one grade 3–4 compared to 43% GC80 and 30% GC50). Interpretation In combination with gemcitabine, carboplatin at AUC6 is not inferior to cisplatin at 80 mg/m 2 in terms of survival. Carboplatin was associated with more adverse events and not with better quality of life. Cisplatin at the lower dose of 50 mg/m 2 has worse survival which is not compensated by better quality of life. ClinicalTrials.gov identifier NCT00112710 . EudraCT Number 2004-003868-30. Cancer Research UK trial identifier CRUK/04/009. [ABSTRACT FROM AUTHOR]

Purpose The protease inhibitor bortezomib attenuates the action of NF-κB and has shown preclinical activity alone and in combination with chemotherapy. Design A Phase I dose-escalation study was performed administering bortezomib (0.7, 1.0, 1.3 and 1.6 mg m on days 1 and 8 from cycle 2 onwards) in combination with Epirubicin 50 mg m intravenously on day 1, Carboplatin AUC 5 day 1 and Capecitabine 625 mg m BD days 1-21 every 21 days (VECarboX regimen), in patients with advanced oesophagogastric adenocarcinoma. The primary objective was to define the maximum tolerated dose (MTD) of Bortezomib when combined with ECarboX. Results 18 patients received bortezomib 0.7 ( n = 6), 1.0 ( n = 3), 1.3 ( n = 6) and 1.6 mg m ( n = 3) and a protocol amendment reducing the capecitabine dose to 500 mg m BD was enacted due to myelotoxicity. Common treatment-related non-haematological adverse events of any grade were fatigue (83.3 %), anorexia (55.6 %), constipation (55.6 %) and nausea (55.6 %). Common Grade 3/4 haematological toxicities were neutropenia (77.8 %) and thrombocytopenia (44.4 %). Objective responses were achieved in 6 patients (33.3 %) and a further 5 patients (27.8 %) had stable disease for >8 weeks. Conclusions The addition of Bortezomib to ECarboX is well tolerated and response rates are comparable with standard chemotherapy. [ABSTRACT FROM AUTHOR]

Is a nurse-led telephone intervention a viable alternative to nurse-led home care and standard care for patients receiving oral capecitabine? Results from a large prospective audit in patients with colorectal cancer Home care nursing has been shown to be a valuable service for patients receiving oral chemotherapy; however, associated costs can be high and telephone-based services may be more cost-effective options. This prospective audit explored the usefulness of a nurse-led telephone intervention for supporting cancer patients treated with Capecitabine, comparing historical findings from a randomised trial evaluating a home-based intervention over standard care with a modified nurse-led telephone follow-up intervention. Self-reported toxicity and service use were assessed in 298 patients who received nurse-led telephone follow-up, compared with historical data from 164 patients (81 receiving standard care and 83 home care intervention). Findings suggested that nurse-led telephone follow-up can potentially lead to reduced toxicity (chest pain, vomiting, oral mucositis, nausea, insomnia) when compared with standard care, and that it has a similar impact on the management of some symptoms when compared with home care (i.e. vomiting, oral mucositis), although it was not as effective as the home care intervention for other toxicities (diarrhoea and insomnia). These encouraging findings need to be explored further using a randomised trial design before we reach any conclusions. Further research should also include a health economics study to assess the cost-effectiveness of the telephone-based services for patients receiving oral chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: The prescribing of oral chemotherapy agents previously available only in the intravenous formulation, such as capecitabine, has afforded many benefits including reduced administration costs and improved patient acceptability. However, it has introduced the new challenge of ensuring patient adherence to therapy. It is therefore necessary to quantify adherence, and with a view to improving services, explore factors that may impact on medication taking behavior.Methods: Patients with a diagnosis of breast or colorectal cancer and prescribed capecitabine were recruited from a UK teaching hospital. Data regarding self-reported adherence, beliefs about medicines, side effects, and satisfaction with information received about capecitabine were recorded.Results: Non-adherence was reported by 23.3% of the 43 participants. Capecitabine therapy was perceived necessary by 97.6%, but almost one-third of participants had strong concerns. Side effects were reported by 80% of participants, with Palmar–Plantar erythrodysesthesia and fatigue most troubling participants. Complete satisfaction with information received was reported by 65% of participants; however, dissatisfaction about how to tell if capecitabine is working and the proposed duration of therapy was expressed by 42.9% and 37.3% of participants, respectively.Conclusions: Adherence to capecitabine is high with a strong conviction that the therapy is necessary. However, concerns were expressed regarding the experience of side effects. Patients have unmet information needs regarding the processes involved with monitoring capecitabine efficacy and determination of therapy duration. Healthcare professionals may therefore wish to consider a greater focus on involving patients in the monitoring of their care with respect to efficacy and planned treatment schedules. [ABSTRACT FROM PUBLISHER]

Abstract: Aim: To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Materials and methods: Between 2001 and 2004, 50 patients with stage III/IV SCCHN (0 to 2 performance status) were enrolled into this study. The capecitabine dose was between 450 and 550mg/m2 twice daily, continuously for 28 days. The radiotherapy dose was 5500cGy in 20 fractions over 4 weeks. No intensity-modulated radiation was used. We evaluated the complete response rate, toxicity, locoregional control, overall survival, disease-free survival and cancer-specific survival. Results: The median age was 55 (range 38–76) years; 72% had stage IV disease. The median follow-up was 6 years on the 30 surviving patients. Eighty-two per cent of patients completed the course of capecitabine and 94% completed prescribed radiotherapy. There were no treatment-related deaths, grade 3/4 haematological or renal toxicity. Five patients developed drug-related grade 3/4 acute toxicity (cardiac, skin, bowel); 47 developed grade 3/4 mucositis from chemoradiotherapy. Twenty-two (44%) patients required tube feeding and the tube dependency rate at 1 year was 6%. The complete response rate at 3 months was 90% (45/50 patients). Relapse occurred in 17/50 (34%) patients by 5 years. The locoregional control, overall survival, cancer-specific survival and disease-free survival rates at 3 years were 78, 72, 82 and 62%, respectively, and at 5 years were 72, 64, 75 and 56%, respectively. Conclusion: This schedule of synchronous capecitabine for locally advanced SCCHN is well tolerated. The local control in this series compares favourably with other synchronous chemoradiotherapy reports. Chronic dysphagia and tube dependence is uncommon with this approach. Capecitabine as targeted therapy given with each fraction of radiotherapy and administered orally may have significant advantages over intravenous, 3 weekly cisplatin. [Copyright &y& Elsevier]

Cytotoxic, also known as antineoplastic, drugs remain an important weapon in the fight against cancer. This study considers the water quality implications for the Thames catchment (United Kingdom) arising from the routine discharge of these drugs after use, down the drain and into the river. The review focuses on 13 different cytotoxic drugs from the alkylating agent, antimetabolite, and anthracycline antibiotic families. A geographic-information-system-based water quality model was used in the present study. The model was informed by literature values on consumption, excretion, and fate data to predict raw drinking water concentrations at the River Thames abstraction points at Farmoor, near Oxford, and Walton, in West London. To discover the highest plausible values, upper boundary values for consumption and excretion together with lower removal values for sewage treatment were used. The raw drinking water cytotoxic drug maximum concentrations at Walton (the higher of the two) representative of mean and low flow conditions were predicted to be 11 and 20 ng/L for the five combined alkylating agents, 2 and 4 ng/L for the three combined antimetabolites, and 0.05 and 0.10 ng/L the for two combined anthracycline antibiotics, respectively. If they were to escape into tap water, then the highest predicted concentrations would still be a factor of between 25 and 40 below the current recommended daily doses of concern. Although the risks may be negligible for healthy adults, more concern may be associated with special subgroup populations, such as pregnant women, their fetuses, and breast-feeding infants, due to their developmental vulnerability. [ABSTRACT FROM AUTHOR]

Looks at the trend of pregnancies with neural-tube defects in women of Indian or Pakistani origin in North Thames (West) Region of the United Kingdom. The effect of red-cell folate deficiency on pregnancy and coronary heart disease; The need for identification of the cause of the trend in North West Thames, education in folate supplementation, and investigation of folate supplementation as a cardioprotective measure.