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.
European Study Group for Pancreatic Cancer
MetadataShow full item record
<h4>Background</h4>The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer.<h4>Methods</h4>We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m<sup>2</sup> gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m<sup>2</sup> oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434.<h4>Findings</h4>Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group.<h4>Interpretation</h4>The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma.<h4>Funding</h4>Cancer Research UK.
Version of record
European Study Group for Pancreatic Cancer
Carcinoma, Pancreatic Ductal
Antineoplastic Combined Chemotherapy Protocols
Aged, 80 and over
Medicine (RMH Smith Cunningham)
License start date
Lancet (London, England), 2017, 389 (10073), pp. 1011 - 1024
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/
Showing items related by title, author, creator and subject.
PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer. Ghaneh, P; Hanson, R; Titman, A; Lancaster, G; Plumpton, C; Lloyd-Williams, H; Yeo, ST; Edwards, RT; Johnson, C; Abu Hilal, M; Higginson, AP; Armstrong, T; Smith, A; Scarsbrook, A; McKay, C; Carter, R; Sutcliffe, RP; Bramhall, S; Kocher, HM; Cunningham, D; Pereira, SP; Davidson, B; Chang, D; Khan, S; Zealley, I; Sarker, D; Al Sarireh, B; Charnley, R; Lobo, D; Nicolson, M; Halloran, C; Raraty, M; Sutton, R; Vinjamuri, S; Evans, J; Campbell, F; Deeks, J; Sanghera, B; Wong, W-L; Neoptolemos, JP (2018-02)<h4>Background</h4>Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The ...
Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma. Neuzillet, C; Tijeras-Raballand, A; Ragulan, C; Cros, J; Patil, Y; Martinet, M; Erkan, M; Kleeff, J; Wilson, J; Apte, M; Tosolini, M; Wilson, AS; Delvecchio, FR; Bousquet, C; Paradis, V; Hammel, P; Sadanandam, A; Kocher, HM (2019-05)Cancer-associated fibroblasts (CAF) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Stromal heterogeneity may explain differential pathophysiological roles of the stroma (pro- versus ...
Sodergren, MH; Mangal, N; Wasan, H; Sadanandam, A; Balachandran, VP; Jiao, LR; Habib, N (2020-11)Advances in surgery, peri-operative care and systemic chemotherapy have not significantly improved the prognosis of pancreatic cancer for several decades. Early clinical trials of immunotherapy have yielded disappointing ...