Toward molecularly selected chemotherapy for advanced gastric cancer: state of the art and future perspectives.
ABSTRACT In the last few years therapeutic options for gastric cancer patients have slowly, but constantly expanded following the introduction of both new chemotherapy agents and innovative indications for treatment. Along with the medical therapy also our knowledge of the molecular mechanisms underlying this disease has progressively improved. However although the available treatment options have undoubtedly increased no clear definitive indications can be made for a standard chemotherapy regimen and we are still unable to accurately select the appropriate treatment for the appropriate patient. Many molecular determinants of response/toxicity to chemotherapy agents have been identified, but only few of them seem to possess the necessary potential for a subsequent application in the clinical practice. Some of these factors have also been indicated as a therapeutic target for a novel class of anti-cancer compounds. This systematic review will analyse available data about these factors with the aim to constitute a starting point for future research.
- Cancer 09/1999; 86(3):547-9. · 5.20 Impact Factor
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ABSTRACT: The aim of this work was to determine whether intratumour contents of thymidine phosphorylase (TP), which converts 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil, and dihydropyrimidine dehydrogenase (DPD), which degrades 5-fluorouracil to inactive molecules, could be useful in predicting the response of patients with metastatic gastric cancer to chemotherapy using 5'-DFUR. Endoscopic biopsy specimens for the measurement of TP and DPD were obtained from the primary lesions before the start of combination chemotherapy, in which 5'-DFUR, cisplatin and mitomycin C were administered. TP and DPD were measured by enzyme-linked immunosorbent assays after the objective responses to chemotherapy had been confirmed. Twenty five patients were enrolled in this study and data for 22 patients in whom responses were confirmed were analysed. The median levels (ranges) of TP and DPD were 80 (4.9-360) and 44 (15-82) U/mg protein, respectively. The median value (range) of TP to DPD ratios was 1.9 (0.25-5.1). Eight patients with a complete or partial response to chemotherapy had significantly higher TP to DPD ratios than did the remaining patients with stable or progressive disease (P = 0.014). When a cut-off level of TP to DPD ratio was defined as the median value, the high-ratio group (n = 11) showed a significantly higher response rate (64% vs. 9.1%, P = 0.024) than the low-ratio group (n = 11). Overall survival of the high-ratio group was significantly longer than that of the low-ratio group (the median survival time; 300 days vs. 183 days, P = 0.047). The efficacy of 5'-DFUR could be optimised by preselecting patients with high TP/ DPD ratios in their tumour tissues, and this would be applicable to the treatment with capecitabine.European Journal of Cancer 08/2004; 40(10):1566-71. · 5.06 Impact Factor
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ABSTRACT: The c-erbB-2 protein is overexpressed in 7% of gastric cancer cases, suggesting that anti-c-erbB-2 antibody therapy (trastuzumab; Herceptin) could be used. We report here a 28-year-old woman with metastatic gastric cancer overexpressing c-erbB-2 (3 + strong membrane staining on immunohistochemistry) who was treated with trastuzumab in combination with chemotherapy. A complete response was obtained with a combination of trastuzumab and oxaliplatin and was maintained with trastuzumab alone for 18 months. The patient relapsed and chemotherapy (capecitabine, docetaxel) was combined with the anti-c-erbB-2 antibody. The patient survived for 4 years with metastatic disease controlled for 2 years by immunochemotherapy. We conclude that the combination of trastuzumab and chemotherapy is efficient in the treatment of metastatic gastric carcinoma with overexpression of the c-erbB-2 protein.Gastric Cancer 02/2005; 8(4):249-52. · 3.99 Impact Factor