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首页> 外文期刊>Clinical cancer research: an official journal of the American Association for Cancer Research >Rationally Designed Pharmacogenomic Treatment Using Concurrent Capecitabine and Radiotherapy for Glioblastoma; Gene Expression Profiles Associated with Outcome
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Rationally Designed Pharmacogenomic Treatment Using Concurrent Capecitabine and Radiotherapy for Glioblastoma; Gene Expression Profiles Associated with Outcome

机译：使用卡培他滨同时放疗合理设计药物基因组学治疗胶质母细胞瘤;与结果相关的基因表达谱

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Purpose: Previous preclinical studies suggested that concurrent capecitabine and radiation could be an effective new treatment modality for glioblastoma (GBM). In the current study, we investigate toxicity and response to this regimen and explore associations between gene expression and patient outcome.Experimental Design: Eighteen newly diagnosed GBM patients received concurrent capecitabine at 625 mg/m2 BID (25% escalation) and irradiation (60 Gy total) for 6 weeks followed by 4 weeks of capecitabine only. Maintenance capecitabine was administered for 14 days every 3 weeks until progression or unacceptable toxicity. Expression analysis of 94 genes involved in capecitabine metabolism and radiation response was done on tissues obtained before therapy. The relationship of gene expression with time-to-progression (TTP) and overall survival (OS) was investigated using univariate Cox proportional hazards regression, semi-supervised principle component analysis, and class prediction modeling.Results: The maximum tolerated dose of capecitabine was 625 mg/m2 BID. Median patient TTP and OS were 247 and 367 days, respectively. Cox regression identified 24 genes significantly (P < 0.025) associated with patient outcome. Semi-supervised principle component analysis identified two patient populations significantly different in both TTP (P = 0.005) and OS (P = 0.015). Class prediction modeling determined that eight genes (RAD54B, MTOR, DCTD, APEX2, TK1, RRM2, SLC29A1, and ERCC6) could collectively classify patients into outcome subgroups with 100% accuracy and precision.Conclusions: Capecitabine and concurrent radiation for newly diagnosed GBM seems to be well tolerated and comparable to temozolomide and radiation. A gene expression profile predictive of patient outcome that may be useful in patient stratification for therapy was also elucidated.
机译：目的：先前的临床前研究表明，同时使用卡培他滨和放疗可能是胶质母细胞瘤（GBM）的有效新治疗方式。在本研究中，我们研究了该方案的毒性和反应性，并探讨了基因表达与患者预后之间的关系。实验设计：18名新诊断的GBM患者接受了625 mg / m2 BID（25％递增）的卡培他滨同时照射（60 Gy）总共6周，然后仅使用卡培他滨4周。每3周给予卡培他滨维持治疗14天，直至进展或出现不可接受的毒性。在治疗前获得的组织上进行了涉及卡培他滨代谢和放射反应的94个基因的表达分析。使用单变量Cox比例风险回归，半监督主成分分析和分类预测模型研究基因表达与进展时间（TTP）和总生存时间（OS）的关系。结果：卡培他滨的最大耐受剂量为出价：625 mg / m2。患者的TTP和OS中位数分别为247和367天。 Cox回归确定与患者预后相关的24个基因（P <0.025）。半监督主成分分析确定了两个患者群体的TTP（P = 0.005）和OS（P = 0.015）显着不同。分类预测模型确定了八个基因（RAD54B，MTOR，DCTD，APEX2，TK1，RRM2，SLC29A1和ERCC6）可以将患者以100％的准确度和准确度归类为结局亚组。具有良好的耐受性，可与替莫唑胺和放射线媲美。还阐明了预测患者结果的基因表达谱，该基因表达谱可用于患者分层治疗。

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