Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial

The Lancet

Volumn 389, Issue 10073, 2017, Pages 1011-1024

  Neoptolemos, John P ^a,b   Palmer, Daniel H ^a,c   Ghaneh, Paula ^b   Psarelli, Eftychia E ^a   Valle, Juan W ^d   Halloran, Christopher M ^a,b   Faluyi, Olusola ^c   O'Reilly, Derek A ^e   Cunningham, David ^f   Wadsley, Jonathan ^g   Darby, Suzanne ^g   Meyer, Tim ^h   Gillmore, Roopinder ^h   Anthoney, Alan ⁱ   Lind, Pehr ^j,k   Glimelius, Bengt ^l   Falk, Stephen ^m   Izbicki, Jakob R ⁿ   Middleton, Gary William ^o   Cummins, Sebastian ^o   Ross, Paul J ^p   Wasan, Harpreet ^q   McDonald, Alec ^r   Crosby, Tom ^s   Ma, Yuk Ting ^t   Patel, Kinnari ^u   Sherriff, David ^v   Soomal, Rubin ^w   Borg, David ^x   Sothi, Sharmila ^y   Hammel, Pascal ^z   Hackert, Thilo ^aa   Jackson, Richard ^a   Büchler, Markus W ^aa   more..

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

^b ROYAL LIVERPOOL UNIVERSITY HOSPITAL   (United Kingdom)

^c CLATTERBRIDGE CENTRE FOR ONCOLOGY   (United Kingdom)

^d CHRISTIE HOSPITAL   (United Kingdom)

^e MANCHESTER ROYAL INFIRMARY   (United Kingdom)

^f ROYAL MARSDEN HOSPITAL   (United Kingdom)

^g WESTON PARK HOSPITAL   (United Kingdom)

^h ROYAL FREE HOSPITAL   (United Kingdom)

ⁱ ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

^j KAROLINSKA INSTITUTE   (Sweden)

^k Center for Clinical Research Sormland   (Sweden)

^l UPPSALA UNIVERSITY   (Sweden)

^m BRISTOL HAEMATOLOGY AND ONCOLOGY CENTRE   (United Kingdom)

ⁿ UNIVERSITY OF HAMBURG   (Germany)

^o ROYAL SURREY COUNTY HOSPITAL   (United Kingdom)

^p GUY S HOSPITAL   (United Kingdom)

^q HAMMERSMITH HOSPITAL   (United Kingdom)

^r BEATSON WEST OF SCOTLAND CANCER CENTRE   (United Kingdom)

^s VELINDRE CANCER CENTRE   (United Kingdom)

^t QUEEN ELIZABETH HOSPITAL   (United Kingdom)

^u CHURCHILL HOSPITAL   (United Kingdom)

^v DERRIFORD HOSPITAL   (United Kingdom)

^w IPSWICH HOSPITAL   (United Kingdom)

^x LUND UNIVERSITY HOSPITAL   (Sweden)

^y UNIVERSITY HOSPITAL COVENTRY   (United Kingdom)

^z BEAUJON HOSPITAL   (France)

^aa UNIVERSITY OF HEIDELBERG   (Germany)

more..

Author keywords

[No Author keywords available]

Indexed keywords

C REACTIVE PROTEIN; CAPECITABINE; GEMCITABINE; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIMETABOLITE; DEOXYCYTIDINE;

ACUTE KIDNEY FAILURE; ADULT; AGED; ANEMIA; ARTICLE; CANCER COMBINATION CHEMOTHERAPY; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER RECURRENCE; CANCER SURGERY; CANCER SURVIVAL; CHEMORADIOTHERAPY; CONTROLLED STUDY; CYST; DIARRHEA; DRUG EFFICACY; DRUG POTENTIATION; DRUG SAFETY; FATIGUE; FEMALE; FEVER; HAND FOOT SYNDROME; HEART DISEASE; HUMAN; INFECTION; INFESTATION; LEUKOCYTE COUNT; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASM; MEDIAN SURVIVAL TIME; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MULTIPLE ORGAN FAILURE; NEUTROPENIA; OPEN STUDY; OVERALL SURVIVAL; PANCREAS ADENOCARCINOMA; PANCREAS RESECTION; PHASE 3 CLINICAL TRIAL; POLYP; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SURGICAL MARGIN; SYSTEMIC THERAPY; THROMBOCYTE; THROMBOEMBOLISM; TUMOR VOLUME; ADJUVANT CHEMOTHERAPY; ANALOGS AND DERIVATIVES; CLINICAL TRIAL; COMPARATIVE STUDY; KAPLAN MEIER METHOD; MIDDLE AGED; MORTALITY; PANCREAS CARCINOMA; PANCREAS TUMOR; TREATMENT OUTCOME; VERY ELDERLY;

ADULT; AGED; AGED, 80 AND OVER; ANTIMETABOLITES, ANTINEOPLASTIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CAPECITABINE; CARCINOMA, PANCREATIC DUCTAL; CHEMOTHERAPY, ADJUVANT; DEOXYCYTIDINE; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; PANCREATIC NEOPLASMS; TREATMENT OUTCOME;

EID: 85011349966     PISSN: 01406736     EISSN: 1474547X     Source Type: Journal    
DOI: 10.1016/S0140-6736(16)32409-6     Document Type: Article

References (30)

1. 1 Kleeff, J, Korc, M, Apte, M, et al. Pancreatic cancer. Nat Rev Dis Primers, 2, 2016, 16022.
2. 2 Cunningham, D, Chau, I, Stocken, DD, et al. Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer. J Clin Oncol 27 (2009), 5513–5518.
3. 3 Von Hoff, DD, Ervin, T, Arena, FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369 (2013), 1691–1703.
4. 4 Sultana, A, Tudur Smith, C, Cunningham, D, et al. Meta-analyses of chemotherapy for locally advanced and metastatic pancreatic cancer. J Clin Oncol 25 (2007), 2607–2615.
5. 5 Conroy, T, Desseigne, F, Ychou, M, et al. Groupe Tumeurs Digestives of Unicancer, PRODIGE Intergroup. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364 (2011), 1817–1825.
6. 6 Neoptolemos, JP, Dunn, JA, Moffitt, DD, et al., for the members of the European Study Group for Pancreatic Cancer (ESPAC). ESPAC-1: A European, randomized controlled study of adjuvant chemoradiation and chemotherapy in resectable pancreatic cancer. Lancet 358 (2001), 1576–1585.
7. 7 Neoptolemos, JP, Stocken, DD, Friess, H, et al., for the members of the European Study Group for Pancreatic Cancer (ESPAC). A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (2004), 1200–1210.
8. 8 Oettle, H, Neuhaus, P, Hochhaus, A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA 310 (2013), 1473–1481.
9. 9 Neoptolemos, JP, Stocken, DD, Tudur Smith, C, et al. Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials. Br J Cancer 100 (2009), 246–250.
10. 10 Valle, JW, Palmer, D, Jackson, R, et al. Optimal duration and timing of adjuvant chemotherapy after definitive surgery for ductal adenocarcinoma of the pancreas: ongoing lessons from the ESPAC-3 study. J Clin Oncol 32 (2014), 504–512.
11. 11 Liao, WC, Chien, KL, Lin, YL, et al. Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis. Lancet Oncol 14 (2013), 1095–1103.
12. 12 Neoptolemos, JP, Cox, T, Bayesian analysis unravels pancreas cancer adjuvant therapy. Lancet Oncol 14 (2013), 1034–1035.
13. 13 Neoptolemos, JP, Stocken, DD, Bassi, C, et al., European Study Group for Pancreatic Cancer. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 304 (2010), 1073–1081.
14. 14 Campbell, F, Smith, RA, Whelan, P, et al. Classification of R1 resections for pancreatic cancer: the prognostic relevance of tumour involvement within 1 mm of a resection margin. Histopathology 55 (2009), 277–283.
15. 15 Sobin, LH, Gospodarowicz, MK, Wittekind, C, (eds.) TNM classification of malignant tumours 7th edn. UICC 7th edn 2009, 2010, Wiley-Blackwell, Oxford.
16. 16 Peto, R, Peto, J, Asymptotically efficient rank invariant test procedures. J R Stat Soc Ser A Stat Soc 135 (1972), 185–207.
17. 17 Cox, DR, Regression models and life tables. J R Stat Soc 34 (1972), 187–220.
18. 18 White, IR, Royston, P, Wood, AM, Multiple imputation using chained equations: issues and guidance for practice. Stat Med 30 (2011), 377–399.
19. 19 Akaike, H, A new look at the statistical model identification. IEEE Trans Automat Contr 19 (1974), 716–723.
20. 20 Schoenfeld, D, Partial residuals for the proportional hazards regression model. Biometrika 69 (1982), 239–241.
21. 21 Schemper, M, Smith, TL, A note on quantifying follow-up in studies of failure time. Contr Clin Trials 17 (1996), 343–346.
22. 22 Trotti, A, Pajak, TF, Gwede, CK, et al. TAME: development of a new method for summarising adverse events of cancer treatment by the Radiation Therapy Oncology Group. Lancet Oncol 8 (2007), 613–624.
23. 23 Henderson, R, Diggle, P, Dobson, A, Joint modelling of longitudinal measurements and event time data. Biostatistics 1 (2000), 465–480.
24. 24 Peto, R, Pike, MC, Armitage, P, et al. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. Analysis and examples. Br J Cancer 35 (1977), 1–39.
25. 25 Uesaka, K, Boku, N, Fukutomi, A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet 388 (2016), 248–257.
26. 26 Sinn, M, Liersch, T, Gellert, K, et al. CONKO-005: Adjuvant therapy in R0 resected pancreatic cancer patients with gemcitabine plus erlotinib versus gemcitabine for 24 weeks—a prospective randomized phase III study. J Clin Oncol, 33(suppl), 2015 abstr 4007.
27. 27 Vivaldi, C, Caparello, C, Musettini, G, et al. First-line treatment with FOLFOXIRI for advanced pancreatic cancer in clinical practice: patients' outcome and analysis of prognostic factors. Int J Cancer, 2016, 10.1002/ijc.30125 published online April 2.
28. 28 Reni, M, Cereda, S, Rognone, A, et al. A randomized phase II trial of two different 4-drug combinations in advanced pancreatic adenocarcinoma: cisplatin, capecitabine, gemcitabine plus either epirubicin or docetaxel (PEXG or PDXG regimen). Cancer Chemother Pharmacol 69 (2012), 115–123.
29. 29 Greenhalf, W, Ghaneh, P, Neoptolemos, JP, et al., European Study Group for Pancreatic Cancer. Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 Trial. J Natl Cancer Inst, 106, 2014, djt347.
30. 30 Capello, M, Lee, M, Wang, H, et al. Carboxylesterase 2 as a determinant of response to irinotecan and neoadjuvant FOLFIRINOX therapy in pancreatic ductal adenocarcinoma. J Natl Cancer Inst, 107, 2015, djv132.