Khokhar Nushmia Z, Jiang Yixing, Benson Al B, Ajani Jaffer A, Mulcahy Mary F
Gastrointest Cancer Res. 2011 May;4(3):96-105.
Gastric cancer-the second most common cause of cancer-related deaths worldwide-is a global health problem. Most cases present at advanced stages and are incurable due to locally advanced or metastatic disease. Although advanced gastric cancer is relatively chemosensitive, a gold standard chemotherapy regimen has yet to emerge, and response rates are of short duration. Cisplatin and 5-fluorouracil (CF) have emerged as the backbone agents in treating this disease. The pivotal V325 trial demonstrated the efficacy benefit of adding docetaxel to CF (DCF). DCF, however, is associated with significant toxicity, making it less tolerable to patients. As a result, docetaxel-containing regimens have been extensively studied and improved upon to mitigate toxicity while maintaining efficacy. Various dosing and scheduling permutations of the original DCF regimen have emerged, and substitutions with other 5-fluorouraci and platinum analogs have been studied. In this review we highlight some of these studies using docetaxel-based regimens as well as new approaches using targeted therapy, including monoclonal antibodies and tyrosine kinase inhibitors. Continuing efforts to improve the efficacy and tolerability of docetaxel-based chemotherapy, combining pharmacokinetic parameters and pharmacogenetic correlates, will further assist in developing optimized regimens. Emerging data using targeted therapy and biologics in combination with chemotherapy are promising, but results of ongoing studies are required to establish the safety and efficacy of these regimens.
胃癌是全球范围内癌症相关死亡的第二大常见原因，是一个全球性的健康问题。大多数病例在晚期出现，由于局部晚期或转移性疾病而无法治愈。尽管晚期胃癌对化疗相对敏感，但尚未出现金标准化疗方案，且缓解率持续时间较短。顺铂和5-氟尿嘧啶（CF）已成为治疗该疾病的主要药物。关键的V325试验证明了在CF（DCF）中添加多西他赛的疗效益处。然而，DCF与显著的毒性相关，使其对患者的耐受性较差。因此，含多西他赛的方案已被广泛研究并改进，以减轻毒性同时保持疗效。原始DCF方案出现了各种给药剂量和时间安排的变化，并且对用其他5-氟尿嘧啶和铂类类似物替代进行了研究。在本综述中，我们重点介绍了一些使用基于多西他赛的方案的研究以及使用靶向治疗的新方法，包括单克隆抗体和酪氨酸激酶抑制剂。结合药代动力学参数和药物遗传学相关性，持续努力提高基于多西他赛的化疗的疗效和耐受性，将进一步有助于制定优化方案。使用靶向治疗和生物制剂联合化疗的新数据很有前景，但需要正在进行的研究结果来确定这些方案的安全性和疗效。
