Docetaxel is a semisynthetic taxane that acts primarily by promoting microtubule assembly and preventing the depolymerization of assembled microtubules, thereby inducing mitotic block and inhibition of cell proliferation. This agent also induces apoptosis and appears to prevent angiogenesis. Although docetaxel has shown efficacy in a wide variety of tumors, it has only recently been evaluated in the treatment of gastrointestinal cancers. Data from preclinical studies have shown that docetaxel has substantial in vitro and in vivo activity against gastric, esophageal, and pancreatic tumors. The cytotoxic activity of docetaxel is generally time- and dose-dependent, and greater than that produced by other chemotherapeutic agents, including paclitaxel and anthracyclines. Studies evaluating combination regimens suggest that docetaxel has additive-to-synergistic antitumor activity against gastrointestinal cancers over that produced by the individual agents, and the increased antitumor activity appears to be schedule-dependent. These data suggest that docetaxel has promising therapeutic activity in the treatment of gastrointestinal cancers and provides a rationale for its inclusion in therapeutic protocols either as a single agent or in combination regimens. In addition to combination regimens with conventional chemotherapeutic agents, early studies with a number of novel molecularly targeted therapies in combination with docetaxel have shown encouraging results. These studies provide a basis for pursuing future clinical trials with docetaxel-based combinations of novel therapies for improving response rates in the treatment of gastrointestinal cancers.

中文翻译：

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多西他赛治疗胃肠道癌的临床前经验。

多西紫杉醇是一种半合成紫杉烷，主要通过促进微管组装和防止组装的微管解聚，从而诱导有丝分裂阻滞和抑制细胞增殖而发挥作用。该剂还诱导凋亡，并似乎预防血管生成。尽管多西紫杉醇已显示出对多种肿瘤的功效，但直到最近才在胃肠道癌的治疗中对其进行了评估。临床前研究的数据表明，多西紫杉醇对胃，食道和胰腺肿瘤具有重要的体外和体内活性。多西紫杉醇的细胞毒活性通常是时间和剂量依赖性的，并且比其他化疗药物（包括紫杉醇和蒽环类药物）产生的细胞毒活性更高。评估联合用药方案的研究表明，多西他赛对胃肠道癌症的累加协同抗肿瘤活性超过单个药物所产生的抗肿瘤活性，并且增加的抗肿瘤活性似乎是时间表依赖性的。这些数据表明，多西紫杉醇在胃肠道癌症的治疗中具有有希望的治疗活性，并为将其作为单一药物或联合治疗方案纳入治疗方案提供了理论依据。除了与常规化学治疗剂的联合治疗方案之外，早期与多种新型分子靶向疗法联合多西他赛的研究也显示出令人鼓舞的结果。