Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Highly Accessed Research article

Modified FOLFOX-6 chemotherapy in advanced gastric cancer: Results of phase II study and comprehensive analysis of polymorphisms as a predictive and prognostic marker

Bhumsuk Keam1, Seock-Ah Im12*, Sae-Won Han1, Hye Seon Ham2, Min A Kim23, Do-Youn Oh12, Se-Hoon Lee12, Jee Hyun Kim12, Dong-Wan Kim12, Tae-You Kim12, Dae Seog Heo12, Woo Ho Kim23 and Yung-Jue Bang12

Author Affiliations

1 Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea

2 Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea

3 Department of pathology, Seoul National University Hospital, Seoul, South Korea

For all author emails, please log on.

BMC Cancer 2008, 8:148  doi:10.1186/1471-2407-8-148

Published: 27 May 2008

Abstract

Background

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 (-6 bp/-6 bp) in TS-3'UTR (55.0% vs. 30.3% in +6 bp/+6 bp or +6 bp/-6 bp, p = 0.034), and C/A or A/A in XPD156 (52.0% vs. 26.1% in C/C, p = 0.038). The -6 bp/-6 bp 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.