Meta-analysis of randomized trials: evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer

BMC Cancer. 2008 Mar 28;8:82. doi: 10.1186/1471-2407-8-82.

Abstract

Background: Single-agent gemcitabine (GEM) is a standard treatment for advanced and metastatic pancreatic cancer. This study examines the question whether GEM-based combination chemotherapy can further improve treatment efficacy.

Methods: A meta-analysis was performed to evaluate randomized trials comparing GEM versus GEM+X (X = cytotoxic agent). Fifteen trials including 4465 patients were eligible for an analysis of overall survival, the primary end-point of this investigation.

Results: The meta-analysis revealed a significant survival benefit for GEM+X with a pooled hazard ratio (HR) of 0.91 (95% CI: 0.85 - 0.97, p = 0.004). The overall test for heterogeneity resulted in p = 0.82 (I2 = 0%). The analysis of platinum-based combinations indicated a HR of 0.85 (95% CI: 0.76 - 0.96, p = 0.010), while for fluoropyrimidine-based combinations the HR was 0.90 (95% CI: 0.81 - 0.99, p = 0.030). No risk reduction was observed in the group of trials combining GEM with irinotecan, exatecan or pemetrexed (HR = 0.99). A meta-analysis of the trials with adequate information on baseline performance status (PS) was performed in five trials with 1682 patients. This analysis indicated that patients with a good PS had a marked survival benefit when receiving combination chemotherapy (HR = 0.76; 95% CI: 0.67 - 0.87; p < 0.0001). By contrast, application of combination chemotherapy to patients with an initially poor PS appeared to be ineffective (HR = 1.08; 95% CI: 0.90 - 1.29, p = 0.40).

Conclusion: The meta-analysis of randomized trials indicated a significant survival benefit when GEM was either combined with platinum analogs or fluoropyrimidines. Based on a preliminary subgroup analysis (representing 38% of all patients included in this meta-analysis), pancreatic cancer patients with a good PS appear to benefit from GEM-based cytotoxic combinations, whereas patients with a poor PS seem to have no survival benefit from combination chemotherapy.

Publication types

  • Comparative Study
  • Meta-Analysis

MeSH terms

  • Aminoacridines / administration & dosage
  • Aminoacridines / adverse effects
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Female
  • Humans
  • Male
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Randomized Controlled Trials as Topic
  • Survival Analysis

Substances

  • Aminoacridines
  • Antimetabolites, Antineoplastic
  • Organoplatinum Compounds
  • Oxaliplatin
  • Deoxycytidine
  • fluoroquinacrine
  • gemcitabine
  • Cisplatin