McCauley D L
Department of Pharmacy, State University of New York, Stony Brook 11794-7310, USA.
Am J Health Syst Pharm. 1996 Mar 1;53(5):521-34; quiz 561-2. doi: 10.1093/ajhp/53.5.521.
The use of high-dose chemotherapy with stem-cell rescue (HDC-SCR) in the treatment of breast cancer is reviewed. The rationale for HDC-SCR in breast cancer is based on the principles of dose response and dose intensity. After conventional-dose chemotherapy, hematopoietic progenitor cells are harvested from the bone marrow or peripheral blood. The patient then undergoes HDC-SCR. Peripheral-blood progenitor cells are becoming the preferred cells for hematopoietic rescue. Most clinical trails of HDC-SCR in metastatic breast cancer have resulted in high overall objective response rates (57-100%), with the highest rates occurring in patients with minimal residual disease or chemotherapy-sensitive disease at the time of high-dose treatment. Most protocols now include induction therapy before HDC-SCR; only patients who show sensitive disease proceed to high-dose therapy. In most studies published to date, the median duration of remission was less than one year from the time of high-dose therapy; however, 10-15% of patients achieved complete remissions lasting two or more years. Most patients relapse, however. Some studies have suggested value of HDC-SCR as consolidation therapy in the adjuvant setting for women at high risk of relapse. Short-term toxicities of HDC-SCR are manageable in experienced hands. Notable long-term adverse effects include leukemia, sterility, pulmonary toxicity, and hemolytic uremic syndrome. Unresolved issues include the utility of purging occult cancer cells from stem-cell-bearing specimens, the best preparative regimen, the implications of autologous graft-versus-host disease, the use of sequential cycles of high-dose chemotherapy, cost-effectiveness, and effectiveness compared with standard therapy. HDC-SCR appears to be a valid option for selected patients with metastatic breast cancer, and in the adjuvant setting for patients at high risk of recurrence. The cost-benefit profile remains to be defined in randomized trials.
本文综述了大剂量化疗联合干细胞救援（HDC-SCR）在乳腺癌治疗中的应用。乳腺癌采用HDC-SCR的理论依据基于剂量反应和剂量强度原则。在常规剂量化疗后，从骨髓或外周血中采集造血祖细胞。然后患者接受HDC-SCR。外周血祖细胞正成为造血救援的首选细胞。大多数转移性乳腺癌HDC-SCR的临床试验总体客观缓解率较高（57-100%），最高缓解率出现在大剂量治疗时残留疾病最少或对化疗敏感的患者中。现在大多数方案在HDC-SCR之前包括诱导治疗；只有显示疾病敏感的患者才进行大剂量治疗。在迄今为止发表的大多数研究中，从大剂量治疗时起缓解的中位持续时间不到一年；然而，10-15%的患者实现了持续两年或更长时间的完全缓解。然而，大多数患者会复发。一些研究表明，HDC-SCR作为复发高危女性辅助治疗中的巩固治疗具有价值。HDC-SCR的短期毒性在经验丰富的医生手中是可控的。显著的长期不良反应包括白血病、不育、肺毒性和溶血尿毒综合征。未解决的问题包括从含干细胞的标本中清除隐匿癌细胞的效用、最佳预处理方案、自体移植物抗宿主病的影响、大剂量化疗序贯周期的使用、成本效益以及与标准治疗相比的有效性。HDC-SCR似乎是转移性乳腺癌特定患者以及复发高危患者辅助治疗中的一个有效选择。成本效益情况仍有待在随机试验中确定。
