Perez R P, Hamilton T C, Ozols R F, Young R C
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Cancer. 1993 Feb 15;71(4 Suppl):1571-80. doi: 10.1002/cncr.2820710424.
Chemotherapy for advanced ovarian cancer remains suboptimal. Despite the improvements in objective response rates realized with cisplatin-based combination chemotherapeutic regimens, most patients still die of refractory cancer. Drug resistance has emerged as the single most important determinant of treatment outcome. Laboratory studies have provided substantial insights into the cellular mechanisms of resistance to the commonly used chemotherapeutic agents. Decreased drug accumulation, metabolic drug inactivation, and repair or tolerance to drug-induced cellular injury all contribute to resistance at the cellular level. Identification of these mechanisms has facilitated the development of specific treatment strategies, many of which are in or nearing clinical trials. These strategies include dose intensification, inhibition of P-glycoprotein function, inhibition of cellular glutathione synthesis, and inhibition of cellular DNA repair. The initial results from clinical trials that use these strategies provide reasonable grounds for optimism. In addition, efforts to identify new drugs with activity against resistant cells continue. One such drug, taxol, has significant activity in tumors refractory to conventional therapy. These approaches offer hope that intensive laboratory and clinical efforts ultimately will translate into real improvements in the efficacy of chemotherapy for ovarian cancer.
晚期卵巢癌的化疗效果仍不尽人意。尽管基于顺铂的联合化疗方案使客观缓解率有所提高，但大多数患者仍死于难治性癌症。耐药性已成为治疗结果的最重要单一决定因素。实验室研究为常用化疗药物的耐药细胞机制提供了大量见解。药物蓄积减少、药物代谢失活以及对药物诱导的细胞损伤的修复或耐受均在细胞水平上导致耐药。对这些机制的识别促进了特定治疗策略的发展，其中许多策略正在进行或即将进入临床试验。这些策略包括剂量强化、抑制P-糖蛋白功能、抑制细胞谷胱甘肽合成以及抑制细胞DNA修复。使用这些策略的临床试验的初步结果提供了乐观的合理依据。此外，寻找对耐药细胞有活性的新药的工作仍在继续。一种这样的药物，紫杉醇，对传统治疗难治的肿瘤具有显著活性。这些方法带来了希望，即密集的实验室和临床努力最终将转化为卵巢癌化疗疗效的真正改善。
