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Translational research in pancreatic ductal adenocarcinoma: current evidence and future concepts

World Journal of Gastroenterology 2014年第31期20卷 10769-10777页

作者： Stephan Kruger Michael Haas Steffen Ormanns Sibylle Bchmann Jens T Siveke Thomas Kirchner Volker Heinemann stefan boeck Department of Internal Medicine Ⅲ and Comprehensive Cancer Center Klinikum Grosshadern Ludwig-Maximilians-University of Munich Department of Pathology Ludwig-Maximilians-University of Munich Department of Internal Medicine Ⅱ Klinikum Rechts der Isar Technical University of Munich

Pancreatic ductal adenocarcinoma(PDA) is one of the major causes for cancer death worldwide. Treatment of metastatic disease remains challenging as only certain patients benefit from advances made with the intensified chemotherapy regimen folinic acid, irinotecan and oxaliplatin, the epidermal growth factor receptor inhibitor erlotinib or the recently FDA-approved nab-paclitaxel. Up to date, no established approach for prediction of treatment response or specific treatment allocation exists. Translational research was able to identify a number of potential biomarkers that might help to improve the dismal prognosis of PDA by facilitating upfront treatment allocation. This topic highlight is focused on current evidence on potential biomarkers for tumor biology, prognosis and prediction of treatment efficacy.

关键词： Biomarker Erlotinib Gemcitabine Human equilibrative nucleoside transporter 1 KRAS Nab-paclitaxel p53 Pancreatic cancer SMAD4 SPARC

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Importance of performance status for treatment outcome in advanced pancreatic cancer

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World Journal of Gastroenterology 2007年第2期13卷 224-227页

作者： stefan boeck Axel Hinke Ralf Wilkowski Volker Heinemann Department of Internal Medicine Ⅲ Klinikum Grosshadern Ludwig-Maximilians- University of Munich Marchioninistrasse 15 81377 Munich Germany WISP Research Institute Karl-Benz-Str. 1 40764 Langenfeld Germany Department of Radiooncology Klinikum Grosshadern Ludwig-Maximilians-University of Munich Marchioninistrasse 15 Munich 81377 Germany

Despite progress in the treatment of advanced and metastatic pancreatic cancer （PC）, the outcome of this disease remains dismal for the majority of patients. Given the moderate efficacy of treatment, prognostic factors may help to guide treatment decisions. Several trials identified baseline performance status as an important prognostic factor for survival. Unfit patients with a Kamofsky performance status （KPS） below 70% only have a marginal benefit from chemotherapy with gemcitabine （Gem） and may often benefit more from optimal supportive care. Once, however, the decision is taken to apply chemotherapy, KPS may be used to select either mono- or combination chemotherapy. Patients with a good performance status （KPS = 90%-100%） may have a significant and clinically relevant survival benefit from combination chemotherapy. By contrast, patients with a poor performance status （KPS ≤ 80%） have no advantage from intensified therapy and should rather receive single-agent treatment.

关键词： Chemotherapy Gemcitabine Pancreatic cancer Performance status Prognostic factor

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UGT1A1 gene polymorphism: Impact on toxicity and efficacy of irinotecan-based regimens in metastatic colorectal cancer

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World Journal of Gastroenterology 2009年第40期15卷 5058-5066页

作者： Christoph Schulz Volker Heinemann Andreas Schalhorn Nikolas Moosmann Thomas Zwingers stefan boeck Clemens Giessen Hans-Joachim Stemmler Department of Haematology & Oncology Ludwig-Maximilians University of MunichCampus Grosshadern Estimate GmbH Konrad-Adenauer-Allee 1

AIM: To investigate the correlation between uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) gene polymorphisms and irinotecan-associated side effects and parameters of drug efficacy in patients with metastatic colorectal cancer (mCRC) receiving a low-dose weekly irinotecan chemotherapeutic regimen. METHODS: Genotypes were retrospectively evaluated by gene scan analysis on the ABI 310 sequencer of the TATAA box in the promoter region of the UGT1A1 gene in blood samples from 105 patients who had received 1st line irinotecan-based chemotherapy for mCRC. RESULTS: The distribution of the genotypes was as follows: wild type genotype (WT) (6/6 ) 39.0%, heterozygous genotype (6/7) 49.5%, and homozygous genotype (7/7) 9.5%. The overall response rate (OR) was similar between patients carrying the (6/7, 7/7) or the WT genotype (6/6) (44.3% vs 43.2%, P = 0.75). Neither time to progression [(TTP) 8.1 vs 8.2 mo, P = 0.97] nor overall survival [(OS) 21.2 vs 18.9 mo, P = 0.73] differed significantly in patients who carried the(6/6) when compared to the (6/7, 7/7) genotype. No significant differences in toxicity were observed: Grade 3 and 4 delayed diarrhoea [(6/7, 7/7) vs (6/6); 13.0% vs 6.2%, P =0.08], treatment delays [(6/7, 7/7) vs (6/6); 25.1% vs 19.3%, P = 0.24] or dose reductions [(6/7, 7/7) vs (6/6); 21.5% vs 27.2%, P = 0.07].CONCLUSION: This analysis demonstrates the non-significant influence of the UGT1A1 gene polymorphism on efficacy and rate of irinotecan-associated toxicity in mCRC patients receiving low-dose irinotecan based chemotherapy.

关键词： Irinotecan Colorectal cancer UGTIA1 Gene polymorphism Toxicity Efficacy Delayed diarrhoea Neutropenia

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行为状态对晚期胰腺癌治疗结局的重要性

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继续医学教育 2007年第9期21卷 1-3页

作者： stefan boeck Axel Hinke Ralf Wilkowski Volker Heinemann 德国慕尼黑大学Klinikum Grosshadern医院内三科 81377

1 引言晚期胰腺癌（PC）是一种难以治愈的疾病，没有合适的治疗方法，其生存期仅限于3～4个月。自从Burris等证明Gem疗效优于大剂量5-氟尿嘧啶（5-Fu）后，Gem单一化疗已成标准治疗方案。多项试验始终支持Gem单一化疗可使中位总生存期... 详细信息

1 引言晚期胰腺癌（PC）是一种难以治愈的疾病，没有合适的治疗方法，其生存期仅限于3～4个月。自从Burris等证明Gem疗效优于大剂量5-氟尿嘧啶（5-Fu）后，Gem单一化疗已成标准治疗方案。多项试验始终支持Gem单一化疗可使中位总生存期（OS）达5～7个月，一年生存率达11％～25％的主张。已有研究人员应用联合化疗改善这一疗效。目前为止，与单一Gem相比，只有两种联合化疗方案：Gem联合埃罗替尼（Erlotinib）以及Gem联合卡培他滨（Capecittabine）可显著延长生存期。

关键词：晚期胰腺癌治疗方法行为状态联合化疗方案 5-氟尿嘧啶标准治疗方案总生存期 Gem

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