Comparison of gemcitabine plus platinum analog with gemcitabine alone in advanced pancreatic cancer

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Abstract

BACKGROUND

Several randomized trials have demonstrated an improved survival in patients with advanced pancreatic cancer treated with gemcitabine plus a platinum analog compared with patients treated with single-agent gemcitabine; however, none of these studies has shown a statistically significant survival advantage of combination therapy. It has become clear that trials enrolling larger numbers of patients are needed to prove a statistically significant benefit of therapy with gemcitabine plus a platinum analog.

OBJECTIVE

To determine whether treatment with gemcitabine plus platinum results in better overall survival (OS) than treatment with single-agent gemcitabine in patients with advanced pancreatic cancer.

DESIGN AND INTERVENTION

This was a pooled analysis of data from the French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer (GISCAD) inter-group study (n=326), which compared gemcitabine plus oxaliplatin with gemcitabine, and the German multicenter study (n=195), which compared gemcitabine plus cisplatin with gemcitabine. Both trials had similar inclusion and exclusion criteria and both recruited patients with histologically proven, unresectable, metastatic or locally advanced pancreatic cancer.

OUTCOME MEASURE

The main outcome measure was OS.

RESULTS

Data were available for 503 patients,252 of whom were treated with gemcitabine plus a platinum analog and 251 of whom were treated with single-agent gemcitabine.Overall response rates were significantly higher in patients receiving gemcitabine plus a platinum analog than among those receiving single-agent gemcitabine (22% vs 14%;P =0.028).The median progression-free survival (PFS)for the study population as a whole was 18 weeks. Pooled univariate analysis of PFS revealed a hazard ratio (HR)of 0.75 in favor of combination therapy (P =0.0030).. Subgroup analysis revealed that the beneficial effect of the combination regimen on PFS was greater in the group of patients with locally advanced disease than in the group of patients with more widespread disease (35 vs 21 weeks;=0.051). In addition, among patients with a good performance status, those receiving combined chemo-therapy experienced a longer median PFS than patients treated with single-agent gemcitabine (33 vs 14 weeks; P =0.013).Median OS for the whole cohort was 33 weeks; OS was significantly greater in patients receiving combination chemo-therapy than in patients receiving gemcitabine alone (HR 0.81, P =0.031). The most important predictors of prognosis were stage of disease (P <0.0001) and performance status (P<0.0001). Subgroup comparisons among patients receiving combination therapy revealed significantly longer OS in patients with good performance status (Eastern Cooperative Oncology Group [ECOG] status 0) than in patients with more-aggressive disease (52 vs 36 weeks; P =0.063).

CONCLUSION

The results of this pooled analysis reveal that, in comparison with single-agent gemcitabine therapy, treatment with the combination of gemcitabine plus a platinum analog significantly improves OS and PFS in patients with advanced pancreatic cancer. Combination therapy seems particularly beneficial in patients with a good performance status.

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