Medline ® Abstracts for References 21,23
Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis.
Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, Wang HP, Tu YK
Lancet Oncol. 2013;14(11):1095. Epub 2013 Sep 12.
BACKGROUND: Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3-4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis.
METHODS: We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression.
FINDINGS: Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42-0·88) for fluorouracil, 0·68 (0·44-1·07) for gemcitabine, 0·91 (0·55-1·46) for chemoradiation, 0·54 (0·15-1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10-1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49-0·84) and gemcitabine (0·59, 0·41-0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12-2·54) or gemcitabine (1·86, 1·04-3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01-169·36).
INTERPRETATION: Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Gemcitabine Adjuvant Therapy for Resected Pancreatic Cancer: A Meta-analysis.
Yu Z, Zhong W, Tan ZM, Wang LY, Yuan YH
Am J Clin Oncol. 2015;38(3):322.
Gemcitabine (GEM) is an approved treatment for unresectable pancreatic cancer; however, its role in treating resected pancreatic cancer is less clear. The aim of this study was to investigate the evidence of the role of adjuvant GEM therapy on survival in resected pancreatic cancer. Four phase III randomized trials of adjuvant GEM in patients with resected pancreatic cancer were identified and the hazard ratio (HR) for overall survival were used in this meta-analysis; 2 studies compared GEM treatment with best supportive care and 2 studies with 5-fluorouracil/folinic acid therapy. The pooled data (n=2017 patients) indicated that the overall survival data were homogenous among the studies (Q=4.371; I=31.37%; P=0. 224). The combined HR significantly favors GEM over the other treatments. The overall HR was 0.88 (range, 0. 720 to 0.940; P=0.014). The results indicate that GEM prolongs overall survival compared with other treatments after the resection of pancreatic cancer.
Departments of *Gastroenterology and Hepatology†Network Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.