Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial.

BACKGROUND: Neoadjuvant chemotherapy before surgery improves survival compared with surgery alone for patients with oesophageal cancer. The OE05 trial assessed whether increasing the duration and intensity of neoadjuvant chemotherapy further improved survival compared with the current standard regimen. METHODS: OE05 was an open-label, phase 3, randomised clinical trial. Patients with surgically resectable oesophageal adenocarcinoma classified as stage cT1N1, cT2N1, cT3N0/N1, or cT4N0/N1 were recruited from 72 UK hospitals. Eligibility criteria included WHO performance status 0 or 1, adequate respiratory, cardiac, and liver function, white blood cell count at least 3 × 10(9) cells per L, platelet count at least 100 × 10(9) platelets per L, and a glomerular filtration rate at least 60 mL/min. Participants were randomly allocated (1:1) using a computerised minimisation program with a random element and stratified by centre and tumour stage, to receive two cycles of cisplatin and fluorouracil (CF; two 3-weekly cycles of cisplatin [80 mg/m(2) intravenously on day 1] and fluorouracil [1 g/m(2) per day intravenously on days 1-4]) or four cycles of epirubicin, cisplatin, and capecitabine (ECX; four 3-weekly cycles of epirubicin [50 mg/m(2)] and cisplatin [60 mg/m(2)] intravenously on day 1, and capecitabine [1250 mg/m(2)] daily throughout the four cycles) before surgery, stratified according to centre and clinical disease stage. Neither patients nor study staff were masked to treatment allocation. Two-phase oesophagectomy with two-field (abdomen and thorax) lymphadenectomy was done within 4-6 weeks of completion of chemotherapy. The primary outcome measure was overall survival, and primary and safety analyses were done in the intention-to-treat population. This trial is registered with the ISRCTN registry (number 01852072) and ClinicalTrials.gov (NCT00041262), and is completed. FINDINGS: Between Jan 13, 2005, and Oct 31, 2011, 897 patients were recruited and 451 were assigned to the CF group and 446 to the ECX group. By Nov 14, 2016, 327 (73%) of 451 patients in the CF group and 302 (68%) of 446 in the ECX group had died. Median survival was 23·4 months (95% CI 20·6-26·3) with CF and 26·1 months (22·5-29·7) with ECX (hazard ratio 0·90 (95% CI 0·77-1·05, p=0·19). No unexpected chemotherapy toxicity was seen, and neutropenia was the most commonly reported event (grade 3 or 4 neutropenia: 74 [17%] of 446 patients in the CF group vs 101 [23%] of 441 people in the ECX group). The proportions of patients with postoperative complications (224 [56%] of 398 people for whom data were available in the CF group and 233 [62%] of 374 in the ECX group; p=0·089) were similar between the two groups. One patient in the ECX group died of suspected treatment-related neutropenic sepsis. INTERPRETATION: Four cycles of neoadjuvant ECX compared with two cycles of CF did not increase survival, and cannot be considered standard of care. Our study involved a large number of centres and detailed protocol with comprehensive prospective assessment of health-related quality of life in a patient population confined to people with adenocarcinomas of the oesophagus and gastro-oesophageal junction (Siewert types 1 and 2). Alternative chemotherapy regimens and neoadjuvant chemoradiation are being investigated to improve outcomes for patients with oesophageal carcinoma. FUNDING: Cancer Research UK and Medical Research Council Clinical Trials Unit at University College London

The Campbells: lordship, literature and liminality

The Campbells have the potential to offer much to the theme of literature and borders, given that the kindred’s astonishing political success in the late medieval and early modern period depended heavily upon the ability to negotiate multiple frontiers: between Highlands and Lowlands; between Gaelic Scotland and Ireland, and, especially after the Reformation, with England and the matter of Britain. This paper will explore the literary dimension to Campbell expansionism, from the Book of the Dean of Lismore in the earlier sixteenth century, to poetry addressed to dukes of Argyll in the earlier eighteenth century. Particular attention will be paid to the literary proclivities of the household of the Campbells of Glenorchy on either side of what appears to be a major watershed in 1550; and to the agenda of the Campbell protégé John Carswell, first post-Reformation bishop of the Isles, and author of the first printed book in Gaelic in either Scotland or Ireland, Foirm na n-Urrnuidheadh (‘The Form of Prayers’), published at Edinburgh in 1567

Scotichronicon, by Walter Bower

Vol. 8, ed. D. E. R. Watt, 1987, xxxii + 410 pp; Vol. 2, ed. John and Winifred MacQueen, 1989, xxx + 528 pp; Vol. 5, ed. Simon Taylor and D. E. R. Watt, 1990, xxx + 520 pp; Vol. 6, ed. Norman F. Shead, Wendy B. Stevenson and D. E. R. Watt, 1991, xxxiv + 506 pp; Aberdeen: Aberdeen University Press

Robert Henryson

Robert Henryson lived between c. 1440 and the opening years of the sixteenth century. William Dunbar's poem “I that in heill was,” composed by 1506, states that death “In Dunfermlyne… has done rovne /With maister Robert Henrisoun” (81-82). Dunbar's description of Henryson as “maister” is echoed in designations given to him on the title-pages of sixteenth-century printed editions of his Fables and Testament of Cresseid. Three charters of the late 1470s from Dunfermline Abbey are also witnessed by a “magister” Robert Henryson, and it is likely that they refer to the poet. The title “Maister ” indicates that Henryson was university educated; this may have been at Glasgow, where there is documentary evidence of a Robert Henryson being admitted as a licentiate in arts and a bachelor in decreets (canon law) in 1462. But Henryson may alternatively or additionally have taken a degree on the continent, like so many Scots of his day. The title-pages of the prints also describe Henryson as schoolmaster in Dunfermline. The grammar school in Dunfermline was linked to its Benedictine abbey, and a schoolmaster there would have had considerable social standing. The charters that name Robert Henryson also refer to him as a notary public. Notaries had authority to make legal deeds and instruments. Depending on their authorization, they could act as recorders at civil or ecclesiastical courts, and many notaries were also clerics, though there is no evidence that Henryson took this route. The precision of the legal references in Henryson's poetry speaks to a close acquaintance with the workings of the law. There is some later evidence for individuals combining the role of schoolmaster and notary public in Scotland.</p