Gemcitabine, oxaliplatin and 5-FU in advanced bile duct and gallbladder carcinoma: two parallel, multicentre phase-II trials

A D Wagner, P Buechner-Steudel, M Moehler, H Schmalenberg, R Behrens, J Fahlke, A Wein, S Behl, O Kuss, G Kleber, W E Fleig, A D Wagner, P Buechner-Steudel, M Moehler, H Schmalenberg, R Behrens, J Fahlke, A Wein, S Behl, O Kuss, G Kleber, W E Fleig

Abstract

Background: Gemcitabine, oxaliplatin and 5-fluorouracil (5-FU) are active in biliary tract cancer and have a potentially synergistic mode of action and non-overlapping toxicity. The objective of these trials was to determine response, survival and toxicity separately in patients with bile duct cancer (BDC) and gallbladder cancer (GBC) treated with gemcitabine/oxaliplatin/5-FU chemotherapy.

Methods: Eligible patients with histologically proven, advanced or metastatic BDC (n=37) or GBC (n=35) were treated with gemcitabine (900 mg m(-2) over 30 min), oxaliplatin (65 mg m(-2)) and 5-FU (1500 mg m(-2) over 24 h) on days 1 and 8 of a 21-day cycle. Tumour response was the primary outcome measure.

Results: Response rates were 19% (95% CI: 6-32%) and 23% (95% CI: 9-37%) for BDC and GBC, respectively. Median survivals were 10.0 months (95% CI: 8.6-12.4) and 9.9 months (95% CI: 7.5-12.2) for BDC and GBC, respectively, and 1- and 2-year survival rates were 40 and 23% in BDC and 34 and 6% in GBC (intention-to-treat analysis). Major grade III and IV adverse events were neutropenia, thrombocytopenia, elevated bilirubin and anorexia.

Conclusion: Triple-drug chemotherapy achieves comparable results for response and survival to previously reported regimens, but with more toxicity.

Figures

Figure 1
Figure 1
Diagram of patient flow.
Figure 2
Figure 2
Overall survival (Kaplan–Meier) for patients with gallbladder cancer (n=35) and bile duct cancer (n=37) (ITT population). +, censored observations.
Figure 3
Figure 3
Quality of life (QoL), as measured by the FACT-Hep global score. Given are the individual (grey) and mean (black) global QoL scores (with 95% confidence interval), as measured by the FACT-Hep questionnaire. High scores represent a high QoL with the maximum achievable value being 180, the minimum value 0. Quality of life was evaluated at baseline, before cycles 3–13 and at the final evaluation. Percentage values within the figure give the fraction of questionnaires divided by the number of patients still in the study at the respective time point.

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