Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: A meta-analysis of published randomised trials

Mari, E.; Floriani, Irene; Tinazzi, Angelo; Buda, Alessandro; Belfiglio, Maurizio; Valentini, Umberto; Cascinu, Stefano; Barni, Sandro; Labianca, Roberto; Torri, Valter

doi:10.1023/a:1008377101672

Cited by 341 publications

(147 citation statements)

References 26 publications

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“…Postoperative adjuvant chemotherapy for gastric cancer has been thoroughly explored over the past 10 -15 years. Several recent meta-analyses have indicated that, even with pooled data, postoperative adjuvant systemic therapy produces only a modest improvement in survival (Earle and Maroun, 1999;Mari et al, 2000;Janunger et al, 2001). Likewise, adjuvant radiotherapy alone has also failed to demonstrate any survival benefit (Hallissey et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

et al. 2003

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Chemoradiation is now used more commonly for gastric cancer following publication of the US Intergroup trial results that demonstrate an advantage to adjuvant postoperative chemoradiotherapy. However, there remain concerns regarding the toxicity of this treatment, the optimal chemotherapy regimen and the optimal method of radiotherapy delivery. In this prospective study, we evaluated the toxicity and feasibility of an alternative chemoradiation regimen to that used in the Intergroup trial. A total of 26 patients with adenocarcinoma of the stomach were treated with 3D-conformal radiation therapy to a dose of 45 Gy in 25 fractions with concurrent continuous infusional 5-fluorouracil (5-FU). The majority of patients received epirubicin, cisplatin and 5-FU (ECF) as the systemic component given before and after concurrent chemoradiation. The overall rates of observed grade 3 and 4 toxicities were 38 and 15%, respectively. GIT grade 3 toxicity was observed in 19% of patients, while haematologic grade 3 and 4 toxicities were observed in 23%. Our results suggest that this adjuvant regimen can be delivered safely and with acceptable toxicity. This regimen forms the basis of several new studies being developed for postoperative adjuvant therapy of gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

et al. 2003

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“…Although several meta-analyses have suggested that adjuvant chemotherapy provides a survival benefit for gastric cancer [1][2][3][4][5][6][7], efficacy has been established for only a few treatments in large clinical trials. Postoperative radiotherapy with 5-FU plus leucovorin has become a standard adjuvant regimen in the US [8], and the perioperative triplet regimen of epirubicin, cisplatin, and 5-FU is standard in the UK [9].…”

Section: Introductionmentioning

confidence: 99%

Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy

et al. 2013

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Background We have previously reported the superior feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer during a prospective phase II study. We report 3-year follow-up data on patients enrolled in this study. Patients and methods Fifty-three patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled into this study. They received oral S-1 (80 mg/m 2 /day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m 2 ) on day 1, repeated every 3 weeks (one cycle). Treatment was initiated within 45 days after surgery and repeated for four cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. Three-year overall survival (OS) and disease-free survival (DFS) were evaluated. Results The OS rate at 3 years was 78.4 % [95 % confidence interval (CI), 67.9-90.6 %] and the DFS rate at 3 years was 66.2 % (95 % CI, 54.4-80.7 %). Subgroup analyses according to disease stage showed a 3-year OS and DFS rate of 85.7 % (95 % CI, 74.9-98.1 %) and 70.8 % (95 % CI, 57.1-87.8 %) for stage IIIA, and 62. 123Gastric Cancer (2014( ) 17:348-353 DOI 10.1007 yielded promising OS and DFS in stage IIIA gastric cancer patients who had undergone D2 gastrectomy. We believe that this regimen is a candidate for future phase III trials studying the optimal adjuvant chemotherapy regimen for stage III gastric cancer.

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“…Until recently there has been relatively little evidence of a survival benefit for established cancer therapies in this disease. However, results from a recent US study have shown a significant survival benefit for the use of adjuvant 5-fluorouracil (5-FU) and radiation in patients following curative resection (MacDonald et al, 2001) and a meta-analysis of the available randomised evidence also supports the use of adjuvant chemotherapy following curative resection (Mari et al, 2000).…”

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Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial

et al. 2002

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This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98 -1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03 -1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00 -2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16 -2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07 -1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted.

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Efficacy of adjuvant chemotherapy after curative resection for gastric cancer: A meta-analysis of published randomised trials

Abstract: Chemotherapy produces a small survival benefit in patients with curatively resected gastric cancer. However, taking into account the limitations of literature based meta-analyses, adjuvant chemotherapy is still to be considered as an investigational approach.

Cited by 341 publications

References 26 publications

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

Adjuvant and neoadjuvant therapy for gastric cancer using epirubicin/cisplatin/5-fluorouracil (ECF) and alternative regimens before and after chemoradiation

Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial

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