Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.
Tandem high-dose chemotherapy supported by hematopoietic progenitor cells yields prolonged survival in stage IV breast cancer.
复制标题
由造血祖细胞支持的串联高剂量化疗可以延长 IV 期乳腺癌的生存期。
作者：
J. Bitran;B. Samuels;L. Klein;S. Hanauer;L. Johnson;J. Martinec;E. Harris;J. Kempler;J. Kempler;W. White
这项II期研究的目的是确定在IV期乳腺癌患者中使用两个(串联)疗程的大剂量烷化剂与骨髓或外周血祖细胞支持的可行性。在常规化疗中达到CR或PR的IV期乳腺癌患者参加了II期试验，大剂量环磷酰胺7500 mg/m2和硫替巴675 mg/m2(C+T)，随后180天内大剂量美法兰(M)140 mg/m2。骨髓和/或GM-CSF动员的外周血造血祖细胞用于支持大剂量C+T和大剂量M。中位年龄为45岁(32-56岁)。中位PS为0，与常规化疗相比，所有患者均获得CR(4/27，15%)或PR(23/27，85%)。所有27名女性均接受了大剂量C+T治疗。主要毒性反应为粘膜炎(81%)和腹泻(81%)；2名患者(7%)死于感染并发症。C+T后，中性粒细胞(ANC>；500个/亩1)和血小板(>；20000个/亩1)血液学恢复的中位时间分别为12天和23天。C+T后，22例患者中有18例接受大剂量M治疗；主要不良反应为恶心、呕吐(70%)和粘膜炎(91%)。ANC血液学恢复的中位时间为13天，血小板恢复的中位时间为18天。大剂量C+T和大剂量M的总有效率为67%(CR，15/27例，56%)和PR*(除持续性溶骨病或骨显像阳性外，所有可测量的疾病完全消失)3/27例(11%)。中位随访时间为24个月，24个月时精算无复发或治疗失败的几率为56%。在30个月时，56%的患者还活着。对于获得CR或PR的患者，24个月后复发或治疗失败的精算成功率为88%。在IV期乳腺癌患者中，与常规化疗相比，获得CR或PR的患者，大剂量联合ABMT化疗可以延长无复发生存期。
The aim of this phase II study was to determine the feasibility of using two (tandem) courses of high-dose alkylating agents with bone marrow or peripheral blood progenitor cell support in women with stage IV breast cancer. Women with stage IV breast cancer who had achieved a CR or PR during conventional chemotherapy were enrolled in a phase II trial of high-dose cyclophosphamide 7500 mg/m2 and thiotepa 675 mg/m2 (C+T) followed within 180 days by high-dose melphalan (M) 140 mg/m2. Bone marrow and/or GM-CSF mobilized peripheral blood hematopoietic progenitor cells were used to support high-dose C+T and high-dose M. Twenty-seven women were enrolled in this trial. The median age was 45 years (range 32-56). The median PS was 0 and all patients had achieved either a CR (4/27, 15%) or PR (23/27, 85%) to conventional chemotherapy. All 27 women underwent high dose C+T. The predominant toxicities were mucositis (81%), and diarrhea (81%); two patients (7%) died from infectious complications. Following C+T, the median time to hematologic recovery for neutrophils (ANC > 500 cells/mu 1) was 12 days and for platelets (>20 000 cell/mu 1), 23 days. Following C+T, 18 of 22 patients received high dose M; the predominant toxicities were nausea, vomiting (70%), and mucositis (91%). The median time to hematologic recovery for the ANC was 13 days and for platelets, 18 days. The overall response after high dose C+T and high dose M was 67% (CR, 15/27 patients (56%) and PR* (complete resolution of all measurable disease but persistent lytic disease or positive bone scan) 3/27 patients (11%). With median follow-up of 24 months, the actuarial freedom from relapse or treatment failure is 56% at 24 months. At 30 months 56% of patients are alive. For patients who achieve a CR or PR* the actuarial freedom from relapse or treatment failure at 24 months is 88%. In women with stage IV breast cancer who attain a CR or PR to conventional chemotherapy, tandem high-dose chemotherapy with ABMT can lead to prolonged relapse-free survival.