Is serum survivin expression a predictive biomarker in locally advanced gastric cancer patients treated with neoadjuvant chemotherapy?

BACKGROUND: The potential prognostic value of survivin is variably reported depending on the gastric cancer. OBJECTIVE: Evaluation of the prognostic and predictive significance of serum survivin and its relation with survival and treatment response rates in patients with locally advanced gastric cancer (LAGC). METHODS: Serum samples were prospectively collected from 50 patients with newly diagnosed LAGC. Serum samples of 32 healthy subjects were also collected as control groups for survivin levels. Serum survivin levels were evaluated at baseline and after three cycles of neoadjuvant chemotherapy in LAGC patients. RESULTS: Median survivin level was 147 IU/L (range = 4.4-4936) at baseline and was 27 IU/L (range = 4.2-4737) after neoadjuvant chemotherapy. The difference between survivin levels of the control group (26 IU/L, range = 3.8-1430) and pre-treatment patient group was statistically significant (p< 0.001). Clinical response to mDCF regimen was classified as progressive (progressive disease) and non-progressive groups (partial response + stable disease). Baseline survivin levels were similar between patients in progressive and non-progressive groups (p= 0.55). Survivin levels were significantly reduced after chemotherapy in non-progressive group (p< 0.001). In contrast, serum survivin levels increased in a stepwise fashion from baseline to post-chemotherapy in patients with progressive disease (p= 0.06). Patients were divided into low and high survivin groups according to baseline median survivin levels. Median DFS was 12.4 and 14.6 months for low and high groups, respectively (p= 0.18). Moreover, median OS was 14.4 and 24.9 months for low and high group, respectively (p= 0.14). CONCLUSION: It can be suggested that serum survivin can be used as a predictor of response to chemotherapy- but not survival- in LAGC patients receiving neoadjuvant mDCF chemotherapy. However, large multicenter prospective studies are required to confirm these results.

Adjuvant bi-weekly combination of cisplatin, infusional 5-fluorouracil and folinic acid followed by concomitant chemoradiotherapy with infusional fluorouracil for high risk operated gastric and gastroesophageal junction adenocarcinoma.

PURPOSE: Chemotherapy and radiotherapy are approved in clinical practice of adjuvant treatment of gastric carcinoma. In present study, we retrospectively evaluated the efficacy and tolerability of an adjuvant treatment protocol including bi-weekly cisplatin, infusional 5-fluorouracil (5-FU) and folinic acid followed by continuous 5-FU infusion during radiotherapy. PATIENTS AND METHODS: Between May 2005 and Dec 2008, 65 curatively resected gastric and gastroesophageal junction adenocarcinoma patients (stage III in 38 and stage IV M0 in 27) received chemotherapy including 50 mg/m2 cisplatin, 200 mg/m2 iv folinic acid, 5-FU 400 mg/m2 iv bolus followed by 5-FU 1600 mg/m2 46h-continuous infusion (CFF) bi-weekly. After 4 cycles of CFF, concomitant 200 mg/m2/day continuous infusion 5-FU and 4500 cGy radiotherapy were administered for 5 weeks. After this chemoradiotherapy an additional 4 cycles of CFF were given. RESULTS: The median follow-up was 15 (6-36) months. Fifty seven (87.7%) patients completed at least 90% of the planned treatment. Median disease free survival was 18 months (95% CI:13.9-22.0) and median overall survival was 19 months (95% CI:15.2-22.8). Common adverse events of all grades were nausea and vomiting (53.8%), leucopenia (42.6%), anemia (30.7%) and diarrhea (20%). The most common grade 3 and 4 toxicities were leucopenia (9.2%), anemia (7.6%), febrile neutropenia (6.1%) and diarrhea (4.6%). CONCLUSION: Bi-weekly CFF chemotherapy followed by continuous 5-FU infusion during radiotherapy is an effective and tolerable regimen for locally advanced operated gastric and gastroesophageal junction adenocarcinoma.