Efficacy of adjuvant XELOX and FOLFOX6 chemotherapy after D2 dissection for gastric cancer

AIM: To compare the efficacy of capecitabine and oxaliplatin (XELOX) with 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX6) in gastric cancer patients after D2 dissection. METHODS: Between May 2004 and June 2010, patients in our gastric cancer database who underwent D2 dissection for gastric cancer at the First Affiliated Hospital of Sun Yat-Sen University were retrospectively analyzed. A total of 896 patients were enrolled into this study according to the established inclusion and exclusion criteria. Of these patients, 214 received the XELOX regimen, 48 received FOLFOX6 therapy and 634 patients underwent surgery only without chemotherapy. Overall survival was compared among the three groups using Cox regression and propensity score matchedpair analyses. RESULTS: Patients in the XELOX and FOLFOX6 groups were younger at the time of treatment (median age 55.2 years; 51.2 years vs 58.9 years), had more undifferentiated tumors (70.1%; 70.8% vs 61.4%), and more lymph node metastases (80.8%; 83.3% vs 57.7%), respectively. Overall 5-year survival was 57.3% in the XELOX group which was higher than that (47.5%) in the surgery only group (P = 0.062) and that (34.5%) in the FOLFOX6 group (P = 0.022). Multivariate analysis showed that XELOX therapy was an independent prognostic factor (hazard ratio = 0.564, P < 0.001). After propensity score adjustment, XELOX significantly increased overall 5-year survival compared to surgery only (58.2% vs 44.2%, P = 0.025) but not compared to FOLFOX6 therapy (48.5% vs 42.7%, P = 0.685). The incidence of grade 3/4 adverse reactions was similar between the XELOX and FOLFOX6 groups, and more patients suffered from hand-foot syndrome in the XELOX group (P = 0.018). CONCLUSION: Adjuvant XELOX therapy is associated with better survival in patients after D2 dissection, but does not result in a greater survival benefit compared with FOLFOX6 therapy.

Role of silencing phosphatase of regenerationg liver-3 expression by microRNA interference in the growth of gastric cancer

Background Accumulated evidences demonstrate that phosphatase of regeneration liver-3 （PRL-3） is associated with metastasis of multiple tumor types, and has been validated as a potential therapeutic target for metastasis. High expression of PRL-3 was implicated in lymph node metastasis of gastric cancer. In the present study, we investigated the role of silencing PRL-3 expression by microRNA （miRNA） interference in gastric cancer growth. Methods RNA interference, mediated by recombinant lentivirus expressing artificial PRL-3 miRNA, was employed to knockdown PRL-3 expression in human SGC7901 gastric cancer cells. MTT assay and tumor implantation experiment were conducted to determine the role of PRL-3 in the proliferation of SGC7901 cells and tumor growth. Results Transfection of recombinant lentivirus expressing artificial PRL-3 miRNA significantly suppressed the proliferation of SGC7901 cells in vitro. The implanted tumor size of the PRL-3 transfection group was （1.92±0.18） cm^3, significantly smaller compared with controls （P 〈0.001）. Conclusions Knockdown of PRL-3 significantly suppressed the proliferation of SGC7901 cells in vitro and tumor growth in vivo. PRL-3 plays a key role in the growth of gastric cancer. PRL-3 should be considered as a potential therapeutic target.

Evaluation of para-aortic nodal dissection for locoregionally advanced gastric cancer with 1-3 involved para-aortic nodes

Background Prophylactic para-aortic nodal dissection （PAND） has no proven benefits for potentially curable advanced gastric cancer.However,the value of therapeutic PAND for involved para-aortic nodes （PANs） in patients with locally advanced gastric cancers has not been determined yet.Methods Between 1998 and 2010,157 gastric cancer patients with 1-3 involved PANs underwent extended D2 （D2＋） lymphadenectomy plus PAND （PAND group,n=69） or extended D2 lymphadenectomy alone （non-PAND group,n=88）.The clinicopathologic features and prognostic data were compared between the two groups.A propensity score-adjusted analysis was used for a balanced comparison.Results The rate of PAN metastasis was 40.6％ （28/69） in the PAND group.The 5-year survival rate was significantly higher in the PAND group than in the non-PAND group （43.7％ vs.31.8％,P=-0.044）.Compared to the non-PAND group,the death hazard ratios in the PAND group were 0.45 （95％ CI 0.274-0.739; P=0.002） and 0.536 （95％ CI 0.328-0.861; P=-0.0097） by multivariate analysis without and with propensity score adjustment respectively.Recurrence rate at 5 years was 39.1％ in the PAND group and 43.2％ in the non-PAND group （P=0.628）.Conclusion Extended D2 lymphadenectomy plus PAND is associated with superior outcomes for advanced gastric cancer patients with 1-3 involved PANs.