Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

Ståhl, Michael; Wilke, H.; Fink, U.; Stuschke, Martin; Walz, Martin K.; Siewert, J R; Molls, M.; Fett, W; Makoski, H. B.; Breuer, Nils; Schmidt, Ulrich; Niebel, W.; Sack, H.; Eigler, F. W.; Seeber, S.

doi:10.1200/jco.1996.14.3.829

Cited by 136 publications

(99 citation statements)

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“…However, cisplatin-based chemotherapy dose not sufficiently improve their overall survival, even when combined with additional irradiation (Stahl et al, 1996;Bosset et al, 1997). The results of these clinical trials suggest that it might be necessary to select the most effective therapy for each case in order to improve survival of patients with OSCC, especially advanced OSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, nm23-H1 is likely to relate to responsiveness to cisplatin-based chemotherapy in patients with OSCC. Stahl et al (1996) have reported that overall 3-year survival rate was 33% in patients with T2-4 oesophageal carcinoma who underwent preoperative chemoradiotherapy and surgery. Likewise, we found that overall 3-year survival rate of 32 OSCC patients included in this study was 39.6%.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the prognosis of patients with locally advanced OSCC remains poor despite significant progress in surgical treatment. Several regimens of cisplatin-based chemotherapy and/or chemoradiotherapy have been applied to treatment of patients with OSCC (Kok et al, 1996;Stahl et al, 1996;Bosset et al, 1997); however, these clinical trials have not shown significant improvement in overall survival so far. These results mean that it may be necessary to distinguish responders from non-responders in cisplatin-based chemotherapy in order to determine a more effective therapy and to improve the poor prognosis of this disease.…”

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The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma

et al. 1999

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Summary Recently, nm23-H1, an anti-metastasis gene, has been reported to correlate with sensitivity to chemotherapeutic agents including cisplatin in human breast and ovarian carcinoma cells. The aim of this study was to evaluate a role for nm23-H1 in responsiveness to cisplatin-based chemotherapy in patients with oesophageal squamous cell carcinoma (OSCC). The expression of nm23-H1 protein was examined immunohistochemically in 32 eligible patients with OSCC who underwent adjuvant chemotherapy with cisplatin, etoposide, and 5-fluorouracil after tumour resection. Fifteen (46.9%) of 32 patients were positive for nm23-H1 staining and 17 (53.1%) were negative. Both disease-free survival and overall survival rates of nm23-H1-negative patients were significantly shorter than in nm23-H1-positive patients (P < 0.01 for both). There was no significant difference in clinicopathologic characteristics between nm23-H1-positive and nm23-H1-negative groups. Multivariate analysis also showed that nm23-H1 expression was the most significant factor for overall survival of OSCC patients included in this study (P = 0.0007). To further study the role of nm23-H1, a human OSCC cell line (YES-2) was transfected with a plasmid containing a fragment of the nm23-H1 cDNA in an antisense orientation. Reduced expression of nm23-H1 protein in the antisensetransfected (AS) clones was found by Western blot analysis as compared to wild-type YES-2 and YES-2/Neo (clone transfected with the neomycin resistance gene alone). MTT (3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide) assay showed that reduced expression of the nm23-H1 protein in AS clones was consistent with the degree of increased resistance to cisplatin but not etoposide or 5-fluorouracil. These data support the conclusion that reduced expression of nm23-H1 may be associated with resistance to cisplatin, suggesting the value of nm23-H1 expression as a prognostic marker for OSCC patients who are to undergo cisplatin-based chemotherapy. © 1999 Cancer Research Campaign Keywords: nm23; cisplatin; chemotherapy; prognosis; oesophageal squamous cell carcinoma 469British Journal of Cancer (1999) 81(3), 469-475 © 1999 Cancer Research Campaign Article no. bjoc.1999 Received 17 September 1998 Revised 1 February 1999 Accepted 21 April 1999Correspondence to: N Iizuka, Department of Bioregulatory Function, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan follow-up periods respectively. One patient was excluded because of loss to follow-up. Therefore, the present study was undertaken in 32 patients retrospectively selected. One course of cisplatinbased chemotherapy consisted of etoposide 120 mg m -2 per day and 5-fluorouracil (5-FU) 500 mg m -2 per day by intravenous (i.v.) continuous infusion on days 3-5, and cisplatin 50 mg m -2 per day by i.v. bolus infusion on days 1 and 8. Seven (21.9%) of 32 patients underwent only 1 course of this regimen because of sideeffects, while 25 patients (78.1%) underwent two course of this regimen following resection. All patient...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma

et al. 1999

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“…The results of this study, together with the criteria for patient selection and study design, have been extensively described elsewhere (Stahl et al, 1996(Stahl et al, , 2005.…”

Section: Patientsmentioning

confidence: 99%

The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma

et al. 2005

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The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy7surgical resection), and the presence of genetic polymorphisms in genes involved in folate metabolism. In total, 68 patients who took part in a prospective multicentric trial received 5-fluorouracil (FU)-based radiochemotherapy, optionally followed by surgery. DNA was extracted from pretherapeutic tumour biopsies and was subsequently genotyped for common genetic polymorphisms of three genes (MTHFR C677T, MTR A2756G, TS tandem repeat polymorphism) involved in folate metabolism and potentially in sensitivity to 5-FU-based chemotherapy. The genotypes were correlated with tumour response to polychemotherapy, radiochemotherapy and with overall survival. Tumours with the MTR wild-type genotype (2756AA) showed a median survival time of 16 months, whereas tumours with an MTR variant genotype (2756AG/2756GG) showed a median survival time of 42 months (P ¼ 0.0463). No prognostic impact could be verified for the genotypes of the MTHFR genes and the TS gene. Among tumours treated with radiochemotherapy and subsequent resection, MTR variant genotype showed higher histopathological response rate than tumours with MTR wild-type genotype (P ¼ 0.0442). In contrast, no significant relationship between clinically determined tumour regression after polychemotherapy and polymorphisms of the three genes under analysis was observed. In conclusion, pretherapeutic determination of the MTR A2756G polymorphism may predict survival of multimodally treated oesophageal squamous cell carcinomas. Determination of MTHFR C677T and TS tandem repeat polymorphism has no predictive value.

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“…Recently, although neo-adjuvant chemoradiotherapy (CRT) followed by oesophagectomy has become widespread after several favourable pilot studies were reported (Poplin et al, 1996;Stahl et al, 1996;Ancona et al, 1997;Ide, 1997), contradictory data have also been published (Bosset et al, 1997;Tamin et al, 1998). A major problem in this context seems to be that a lower rate of cancerrelated deaths after combined treatment is counterbalanced by a higher rate of treatment-associated mortality.…”

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confidence: 99%

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

et al. 2002

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The ability to predict patients' responses to chemoradiotherapy by analyzing pre-treatment biopsy specimens would be valuable for managing oesophageal squamous-cell cancer. To this end, the expression of p53, thymidine phosphorylase and vascular endothelial cell growth factor was analyzed by immunohistochemistry in 52 patients with oesophageal squamous-cell cancer prior to chemoradiotherapy. Treatment consisted of radiotherapy (40 Gy) and 5 day-infusion of 5-Fluorouracil (500 mg m 72 per day) combined with cisplatin (10 mg m 72 per day). Following treatment, imaging and endoscopic reassessment was performed to establish treatment response. Thirty-one patients underwent radical surgery and 21 patients were treated with an additional 20 Gy of radiotherapy. Of the tumours studied, 58% were p53-positive, 40% thymidine phosphorylase-positive and 44% vascular endothelial cell growth factor-positive. A clinical response was observed in 36 patients (69%) and was negatively associated with thymidine phosphorylase expression (P=0.02) and vascular endothelial cell growth factor expression (P50.001). However, the 5-year survival rate was significantly lower only in patients with vascular endothelial cell growth factor-positive tumours (P=0.037). Multivariate analysis identified vascular endothelial cell growth factor as a significant independent prognostic factor (P=0.0147). These results suggest that expression of angiogenic factors has predictive value for the treatment response and outcome of patients with oesophageal cancer.

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Combined preoperative chemotherapy and radiotherapy in patients with locally advanced esophageal cancer. Interim analysis of a phase II trial.

Cited by 136 publications

References 15 publications

The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma

The nm23-H1 gene as a predictor of sensitivity to chemotherapeutic agents in oesophageal squamous cell carcinoma

The prognostic significance of genetic polymorphisms (Methylenetetrahydrofolate Reductase C677T, Methionine Synthase A2756G, Thymidilate Synthase tandem repeat polymorphism) in multimodally treated oesophageal squamous cell carcinoma

Expression of angiogenic factors predicts response to chemoradiotherapy and prognosis of oesophageal squamous cell carcinoma

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