Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker
The objective of this study was to evaluate the efficacy and toxicity of infusional 5-fluorouracil (5-FU), folinic acid and oxaliplatin (modified FOLFOX-6) in patients with advanced gastric cancer (AGC), as first-line palliative combination chemotherapy. We also analyzed the predictive or prognostic value of germline polymorphisms of candidate genes associated with 5-FU and oxaliplatin.
Methods: Seventy-three patients were administered a 2 hour infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2) followed by a 46 hour continuous infusion of 5-FU (2,400 mg/m2).
Genomic DNA from the patients' peripheral blood mononuclear cells was extracted. Ten polymorphisms within five genes were investigated including TS, GSTP, ERCC, XPD and XRCC.
Results: The overall response rate (RR) was 43.8%. Median time to progression (TTP) and overall survival (OS) were 6.0 months and 12.6 months, respectively.
Toxicities were generally tolerable and manageable. The RR was significantly higher in patients with a 6-bp deletion homozygote (-6bp/-6bp) in TS-3'UTR (55.0% vs.
30.3% in +6bp/+6bp or +6bp/-6bp, p=0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p=0.038).
The -6bp/-6bp in TS-3'UTR was significantly associated with a prolonged TTP and OS. In a multivariate analysis, the 6-bp deletion in TS-3'UTR was identified as an independent prognostic marker of TTP (hazard ratio = 0.561, p=0.032).
Conclusion: Modified FOLFOX-6 chemotherapy appears to be active and well tolerated as first line chemotherapy in AGC patients.
The 6-bp deletion in TS-3'UTR might be a candidate to select patients who are likely to benefit from 5-FU based modified FOLFOX-6 in future large scale trial.
Author: Bhumsuk Keam, Seock-Ah Im, Sae-Won Han, Hye Seon Ham, Min A Kim, Do-Youn Oh, Se-Hoon Lee, Jee Hyun Kim, Dong-Wan Kim, Tae-You Kim, Dae Seog Heo, Woo Ho Kim and Yung-Jue Bang
Credits/Source: BMC Cancer 2008, 8:148
Published on: 2008-05-28
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