Tawbi Hussein A, Kirkwood John M
Melanoma and Skin Cancer Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Semin Oncol. 2007 Dec;34(6):532-45. doi: 10.1053/j.seminoncol.2007.09.008.
Since the original approval of dacarbazine for the treatment of metastatic malignant melanoma, considerable effort has been expended in attempts to improve survival. This end point is the most unequivocal and ultimately meaningful for patients with cancer but has been one upon which clinical trials conducted to date have failed to demonstrate a meaningful impact. Little data regarding quality of life are currently available, but outside the setting of a clinical trial, a convenient single-agent dose regimen of dacarbazine is probably the best approach, currently. Targeted agents that are designed to abrogate various pathways implicated in signal transduction, cell cycle checkpoints, immunomodulation, and DNA repair offer promising novel approaches for the treatment of metastatic melanoma. However, cytotoxics may be essential backbones for combinations with these molecules. Phase II designs with targeted agents may require new and innovative end points to identify activity. The rational use of agents capable of abrogating drug resistance offers other opportunities for systemic chemotherapy that may then give rise to more rationally developed combinations.
自达卡巴嗪最初获批用于治疗转移性恶性黑色素瘤以来，人们为提高生存率付出了巨大努力。这一终点对癌症患者而言是最明确且最终意义重大的，但迄今为止开展的临床试验均未能证明其有显著影响。目前关于生活质量的数据很少，但在临床试验之外，达卡巴嗪方便的单药剂量方案可能是目前最好的方法。旨在消除涉及信号转导、细胞周期检查点、免疫调节和DNA修复的各种途径的靶向药物为转移性黑色素瘤的治疗提供了有前景的新方法。然而，细胞毒性药物可能是与这些分子联合使用的重要基础。靶向药物的II期设计可能需要新的创新终点来确定活性。合理使用能够消除耐药性的药物为全身化疗提供了其他机会，进而可能产生更合理开发的联合治疗方案。
