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Meta-Analysis Suggests Fluorouracil or Gemcitabine Is Optimum Adjuvant Treatment for Pancreatic Cancer

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Key Points

  • Chemotherapy with fluorouracil or gemcitabine was the optimum adjuvant treatment for pancreatic adenocarcinoma and reduced mortality after surgery by about one-third.
  • Chemoradiation plus chemotherapy was less effective in prolonging survival and was more toxic than chemotherapy.

A meta-analysis reported in The Lancet Oncologyby Wei-Chih Liao, MD, of National Taiwan University Hospital and colleagues indicates that fluorouracil (5-FU) or gemcitabine is optimal adjuvant therapy for pancreatic adenocarcinoma. Chemoradiation was associated with poorer survival and chemoradiation plus chemotherapy provided no significant additional survival benefit at the cost of greater toxicity.  

Study Details

The systematic review and meta-analysis included 9 studies comparing 5-FU, gemcitabine, chemoradiation, and chemoradiation plus 5-FU or gemcitabine with each other or with observation. Overall survival and grade 3 or 4 toxicities were analyzed using a random-effects Bayesian network meta-analysis.

Overall Survival Outcomes

Compared with observation, the hazard ratios (HRs) for death were 0.62 (95% credible interval [CI] = 0.42–0.88) for 5-FU, 0.68 (95% CI = 0.44–1.07) for gemcitabine, 0.91 (95% CI = 0.55–1.46) for chemoradiation, 0.54 (95% CI = 0.15–1.80) for chemoradiation plus 5-FU, and 0.44 (95% CI = 0.10–1.81) for chemoradiation plus gemcitabine.

The proportion of patients with positive lymph nodes, but not positive resection margins or poorly differentiated or undifferentiated tumors, was inversely associated with the overall survival benefit of adjuvant treatments over observation. The hazard ratios for death increased by 2.5% (95% CI = 0.0–5.3)  per 1% increase in the proportion of patients with positive lymph nodes. After adjustment for this factor, 5-FU (HR = 0.65, 95% CI = 0.49–0.84) and gemcitabine (HR = 0.59, 95% CI = 0.41–0.83) provided a significant overall survival benefit over observation, whereas chemoradiation was associated with significantly poorer overall survival compared with 5-FU (HR = 1.69, 95% CI = 1.12–2.54) and gemcitabine (HR = 1.86, 95% CI = 1.04–3.23). Chemoradiation plus 5-FU did not improve overall survival compared with 5-FU (HR = 0.98, 95% CI = 0.42–2.17) or gemcitabine (HR = 1.08, 95% CI = 0.41–2.69) and chemoradiation plus gemcitabine did not improve overall survival compared with 5-FU (HR = 0.80, 95% CI = 0.30–2.04) or gemcitabine (HR = 0.88, 95% CI = 0.29–2.52).

Toxicity Ranking

Treatment rankings from least to most toxic were chemoradiation, gemcitabine, 5-FU, chemoradiation plus 5-FU, and chemoradiation plus gemcitabine. Odds ratios for grade 3 or 4 nonhematologic adverse effects did not significantly differ in between-treatment comparisons. The only significant difference in between-treatment comparisons for grade 3 or 4 hematologic adverse effects was between chemoradiation plus gemcitabine and chemoradiation plus 5-FU (odds ratio = 13.33, 95% CI = 1.01–169.36).

The investigators concluded, “Our results suggest that adjuvant chemotherapy with fluorouracil or gemcitabine provides an overall survival advantage over observation or chemoradiation, whereas adding chemoradiation to chemotherapy provides little further survival benefit, but increases toxic effects.”

The corresponding author for this study is Yu-Kang Tu, PhD, of National Taiwan University.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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