Prospective randomized trial of short-term neoadjuvant chemotherapy for advanced gastric cancer

Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohnohigashi, Osaka-Sayama, Osaka 589-8511, Japan.
European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology (Impact Factor: 3.01). 10/2010; 36(10):963-8. DOI: 10.1016/j.ejso.2010.06.012
Source: PubMed


We performed short-term neoadjuvant chemotherapy (s-NAC) to examine whether anticancer drugs can change the proliferative ability of cancer cells in gastric cancer patients.
Chemotherapy was performed for 72 h before gastrectomy in 63 gastric cancer patients. Patients were classed into four groups: Group F, 16 cases who received a single administration of 5-fluorouracil (5-FU); Group C, 15 cases who received a single administration of cis-diamminedichloroplatinum (CDDP; cisplatin); Group FC, 16 cases who received both 5-FU+CDDP; and a Control group, 16 cases who did not receive chemotherapy. We reviewed neoadjuvant biopsy tissue and gastric cancer tissue delivered by operation in these cases. The TUNEL method and immunohistochemistry with an anti-MIB-1 antibody were used to evaluate cellular apoptosis and proliferative ability, respectively. The apoptotic index (AI) and an MIB-1 index (MI) were also calculated.
There were no differences in AI or MI in biopsy tissue between the groups. The AI of gastric cancer tissue in Group FC was significantly higher than in the other groups (P < 0.01). The MI of Group FC was significantly lower than in the other groups (P < 0.05). In addition, after s-NAC operation there was a significant inhibition of proliferative potency and an induction of apoptosis in Group FC.
Combination of CDDP and 5-FU reduced proliferative potency and increased cellular apoptosis in gastric cancer cells.

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    • "patients experienced NAC-related grade3/4 side-effects, including anorexia, leukopenia, thrombocytopenia, liver dysfunction and massive bleeding from GC. In Imano's study [48], no severe side effects of NAC happened. Schuhmacher [49] reported 8 (32%) patients experiencing toxicity (2 renal toxicity [maximum grade 2], 1 cardiac toxicity [grade 3], 4 nausea [maximum grade 3] and vomiting [maximum grade 3], and 1 neutropenia [grade 2]). "
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    ABSTRACT: The effect of neoadjuvant chemotherapy (NAC) on Gastric carcinoma (GC) has been extensively studied, while its survival and surgical benefits remain controversial. This study aims to perform a meta-analysis of high-quality randomized controlled trials (RCTs), comparing efficacy, safety and other outcomes of NAC followed by surgery with surgery alone (SA) for GC. We systematically searched databases of MEDLINE, EMBASE, The Cochrane Library and Springer for RCTs comparing NAC with SA when treating GC. Reference lists of relevant articles and reviews, conference proceedings and ongoing trial databases were also searched. Primary outcomes were 3-year and 5-year survival rates, survival time, and total and perioperative mortalities. Secondary outcomes included down-staging effects, R0 resection rate, and postoperative complications. Meta-analysis was conducted where possible comparing items using relative risks (RRs) and weighted mean differences (WMDs) according to type of data. NAC-related objective response, safety and toxicity were also specifically analyzed. A total of 9 RCTs comparing NAC (n = 511) with SA (n = 545) published from 1995 to 2010 were identified. SA tended to be accompanied with higher overall mortality rate than NAC (46.03% vs 40.61%, RR: 0.83, 95% CI: 0.65-1.06, P = 0.14). Significantly, higher incidence of cases without regional lymph node metastasis observed upon resection were achieved among patients receiving NAC than those undergoing SA (25.68% vs 16.95%, RR: 1.92, 95% CI: 1.20-3.06, P = 0.006). All other parameters were comparable. Of the evaluable patients, 43.0% demonstrated either complete or partial response. The comprehensive NAC-related side-effect rate was 18.2% among patients available for safety assessment. NAC contributes to lowering nodal stages, and potentially reduces overall mortality. Response rate may be an important influential factor impacting advantages, with chemotherapy-related adverse effects as a drawback. This level 1a evidence doesn't support NAC to outweigh SA in terms of survival and surgical benefits when dealing with GC.
    Full-text · Article · Jan 2014 · PLoS ONE
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    Full-text · Chapter · Dec 2011
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    ABSTRACT: Background: The objective of the present meta-analysis was to estimate the magnitude of survival benefits of neoadjuvant chemotherapy (NAT) in resectable cancer of the gastric and gastroesophageal junction. Materials and methods: We searched PubMed, Embase, the Cochrane Library, ISI Web of Knowledge, Chinese biomedical literature database, Chinese Scientific Journals full-text database of retrieved articles from their inception to 2013. Two reviewers independently retrieved study and data extraction of included studies. Results regarding the overall survival and progression-free survival in the meta-analysis were expressed as hazard ratios (HRs) with 95% confidence intervals (CI). Results: Twelve randomized control trials (n=1755) were eligible for final meta-analysis. NAT was associated with a statistically significant benefit in terms of overall survival (HR=0.72; 95% CI, 0.56-0.93, P=0.01), progression-free survival (HR=0.73; 95% CI, 0.62-0.87, P=0.0003), 5-year survival rate [relative risk (RR)=1.36; 95% CI, 1.10-1.67, P=0.0004], and curative resection rate (RR=1.11; 95% CI, 1.03-1.20, P=0.009). Five-year survival rate increased from 30% to 42% with NAT. No significant difference with regards to overall postoperative complications rate (RR=1.08; 95% CI, 0.92-1.27, P=0.28) was found between 2 groups. Conclusion: There is convincing evidence for a survival benefit of NAT over surgery alone in patient with cancer of the gastric and gastroesophageal junction.
    No preview · Article · Aug 2014 · Journal of Clinical Gastroenterology