O'Day Steven, Boasberg Peter
Department of Medicine, Keck School of Medicine, University of Southern California, 1975 Zonal Avenue, KAM 500, Los Angeles, CA 90089-9034, USA.
Surg Oncol Clin N Am. 2006 Apr;15(2):419-37. doi: 10.1016/j.soc.2005.12.002.
The management of metastatic melanoma in 2005 remains a major clinical challenge. Multidisciplinary treatment planning and careful attention to sites of metastases, tumor biology, and comorbid conditions are critical to making the best clinical decisions for individual patients. No standard of care exists because no systemic therapies have yet shown efficacy in phase III trials. Single-agent or combination chemotherapy has not impacted over-all survival, and response rates are of short duration. High-dose IL-2 produces durable responses in a small subset (7%) of highly selected patients and has considerable toxicity and quality-of-life trade-offs. Biochemotherapy results in overall higher responses, but its impact on overall survival has been disappointing and its toxicity and expense are considerable. Re-searchers are further investigating biochemotherapy modifications with maintenance biotherapy and CNS consolidation in effort to increase durability of responses and prevent or delay the devastating sequela of CNS metastases. Despite a disappointing past, the advancement of science and a better understanding of critical cellular targets and pathways make the future of melanoma research encouraging. Clinical trials are actively studying novel immune potentiators, cytotoxics, and targeted therapies. Combinations of these new agents will likely be necessary to advance the treatment of the dis-ease. All patients should be encouraged to participate in clinical trials.
2005年转移性黑色素瘤的治疗仍是一项重大临床挑战。多学科治疗规划以及对转移部位、肿瘤生物学和合并症的密切关注对于为个体患者做出最佳临床决策至关重要。由于尚无系统疗法在III期试验中显示出疗效，因此不存在标准治疗方案。单药或联合化疗对总生存期没有影响，且缓解率持续时间短。高剂量白细胞介素-2在一小部分（7%）经过严格筛选的患者中产生持久缓解，但有相当大的毒性且会影响生活质量。生物化疗导致总体缓解率更高，但其对总生存期的影响令人失望，且毒性和费用相当可观。研究人员正在进一步研究生物化疗的改良方法，包括维持生物治疗和中枢神经系统巩固治疗，以提高缓解的持久性，并预防或延迟中枢神经系统转移的灾难性后果。尽管过去令人失望，但科学的进步以及对关键细胞靶点和信号通路的更好理解使黑色素瘤研究的未来充满希望。临床试验正在积极研究新型免疫增强剂、细胞毒素和靶向疗法。可能需要联合使用这些新药物来推进该疾病的治疗。应鼓励所有患者参加临床试验。
