A new paradigm of chemotherapy for gastric cancer: speeding up, and more clinical trials to catch up
A new paradigm of chemotherapy for gastric cancer: speeding up, and more clinical trials to catch up
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胃癌化疗新范式：加速推进，更多临床试验迎头赶上
作者：
J. Sakamoto
这是一种有效的治疗手段，并加快了评估新治疗方式的进程。但是，我们应该研究什么样的新型治疗方式呢？与其他主要实体肿瘤相比，我们如何才能弥补在建立胃癌治疗模式方面的延误，而不走十年前不成功的迂回道路[7]？紫杉醇被认为是一种独特的细胞毒药物，有望成为治疗胃癌的新型化疗药物之一。为了了解紫杉醇的作用，有必要对其基础和临床药理进行综述。紫杉醇是一种新的二萜类化合物，它含有一个复杂的环系，称为紫杉环，与一个复杂的酯链相连。这种紫杉烷衍生物是微管蛋白结合剂类的成员。但是，与促进微管解体的微管结合家族中的其他药物不同，紫杉醇将平衡转向微管组装，并通过防止解聚来稳定微管[8，9]。实验研究表明，紫杉醇具有多种生物活性，不同浓度的紫杉醇具有不同的作用机制。在较高剂量下，紫杉醇将分裂细胞阻断在G2/M期，抑制微管解聚，并直接杀死肿瘤细胞。在较低浓度下，紫杉醇可诱导细胞凋亡[10，11]、抑制血管生成和免疫调节。紫杉醇作为治疗卵巢癌、乳腺癌、肺癌的主要药物之一，已广泛应用于临床。由于紫杉醇的作用机制与氟嘧啶类药物完全不同，该药物在治疗胃癌方面可能会有相当大的改善。紫杉醇的安全性已经得到了很好的证实。在最初的临床试验中观察到的严重过敏反应的发生率通过预防性给予抗过敏药物显著减少，其中包括国际和日本胃癌协会2002年的皮质类固醇
tarium of useful agents and to accelerate the process of evaluating new treatment modalities. But what type of novel treatment modalities should we examine? And how can we make up for the delay in establishing gastric cancer treatment modalities, compared with those for other major solid tumors, without going by a roundabout way that was not successful a decade ago [7]? Paclitaxel, which has been heralded as a unique cytotoxic agent, could be one of the most promising novel chemotherapeutic agents for gastric cancer. To understand the effect of paclitaxel, a review of its basic and clinical pharmacology is necessary. Paclitaxel is a novel diterpenoid that contains a complex ring system, called a taxane ring, coupled with a complex ester chain. This taxane derivative is a member of the tubulin-binding agent class. But, unlike other agents in the tubulinbinding family that promote microtubule disassembly, paclitaxel shifts the equilibrium toward microtubule assembly, and stabilizes microtubules by preventing depolymerization [8,9]. Experimental studies have shown that paclitaxel has multiple biological activities, and different mechanisms of action are speculated depending on the concentration of paclitaxel. At a higher dose, paclitaxel blocks dividing cells in the G2/M phase, inhibits microtubular depolymerization, and directly kills tumor cells. At a lower concentration, paclitaxel induces apoptosis [10,11] anti-angiogenesis, and immunomodulation. Paclitaxel has already been used extensively in clinical practice, as one of the key drugs for the treatment of ovarian cancer, breast cancer, and lung cancer. As paclitaxel possesses a totally different mechanism of action compared with that of the fluoropyrimidines, the drug may bring about considerable improvements in the treatment of gastric cancer. The safety profile of paclitaxel has been well established. The incidence of severe hypersensitivity reactions observed in the initial clinical trials has been significantly reduced by the prophylactic administration of antiallergy medication, including a corticosteroid 2002 by International and Japanese Gastric Cancer Associations
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DOI：
10.1016/s1278-3218(02)00178-6
发表时间：
2002-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
J. Macdonald;S. Smalley;J. Benedetti;S.A Hundhal;N. Estes;G.N Stemmermannn;D. Haller;J. Ajani-
通讯作者：
J. Macdonald;S. Smalley;J. Benedetti;S.A Hundhal;N. Estes;G.N Stemmermannn;D. Haller;J. Ajani-
影响因子：
45.3
作者：
GIANNI, L;KEARNS, CM;EGORIN, MJ
通讯作者：
EGORIN, MJ
影响因子：
11.2
作者：
K. Torres;S. B. Horwitz
通讯作者：
K. Torres;S. B. Horwitz
每周一次紫杉醇联合或不联合放射治疗：毒性、药代动力学和反应。
DOI：
--
发表时间：
1996
期刊：
Seminars in oncology.
影响因子：
--
作者：
Glantz,MJ;Choy,H;Akerley,W;Kearns,CM;Egorin,MJ;Rhodes,CH;Cole,BF
通讯作者：
Cole,BF