Gisselbrecht C, Extra J M, Lotz J P, Devaux Y, Janvier M, Peny A M, Guillevin L, Bremond D, Delain M, Herbrecht R, Lepage E, Maraninchi D
Hôpital Saint-Louis, Paris, France.
Bone Marrow Transplant. 1996 Nov;18(5):857-63.
Dose-intensive treatment followed by ABMT is currently used in different approaches to treat breast cancer patients. An active non cross-resistant regimen combining cyclophosphamide (C), mitoxantrone (M) and melphalan (A) (CMA), was developed as the conditioning regimen before ABMT. The purpose of this phase II study was to evaluate this protocol and the duration of its effect in metastatic patients, who responded to chemotherapy. Criteria for inclusion included histologically documented breast cancer, age < 55 years and the first detection of measurable metastatic lesions. Following first-line chemotherapy in responding patients, histologically negative bone marrow was collected and cryopreserved. Then, intensification with cyclophosphamide (120 mg/kg), mitoxantrone (60 mg/m2), and melphalan (140 mg/m2) was followed by ABMT. Sixty-one metastatic breast cancer patients with a mean age of 40 years were included. Sites of measurable metastases included: liver 24, lung 14, central nervous system four, pleura three, skin six, and chest wall six, nodes eight and bone marrow one. Nineteen patients had lesions in two or more sites, and 22 had bone involvement. The response of 60 patients could be evaluated: before ABMT 31 were in clinical complete response (CR), 22 in partial response > 50% (PR), and seven had new progression. After ABMT, 36 patients were in CR, 16 in PR, one progressed and one was stable. Seven (11.5%) toxic deaths occurred. Mean time for hematological recovery was 32.5 days, without hematopoietic growth factors. Median survival was 33 +/- 9.4 months from the start of therapy, and 25.7 +/- 4.6 months from the date of ABMT. Median event-free survival was 20 months from the start of therapy, and 13 +/- 2 months from ABMT. With a median follow-up of 51 months, probability of actuarial survival, measured from the beginning of initial chemotherapy, was 36%, and event-free survival was 18%. In metastatic breast cancer responding to chemotherapy, high-dose consolidation with CMA and ABMT resulted in a median survival of 33 months. These results lay the ground work for evaluation in a randomized trial in metastatic breast cancer.
剂量密集治疗后进行自体骨髓移植（ABMT）目前被用于多种治疗乳腺癌患者的方法中。一种由环磷酰胺（C）、米托蒽醌（M）和美法仑（A）组成的有效的非交叉耐药方案（CMA）被开发出来作为ABMT前的预处理方案。这项II期研究的目的是评估该方案及其对化疗有反应的转移性患者的疗效持续时间。纳入标准包括组织学确诊的乳腺癌、年龄<55岁以及首次检测到可测量的转移性病变。在有反应的患者接受一线化疗后，收集组织学阴性的骨髓并冷冻保存。然后，给予环磷酰胺（120mg/kg）、米托蒽醌（60mg/m²）和美法仑（140mg/m²）进行强化治疗，随后进行ABMT。纳入了61例平均年龄为40岁的转移性乳腺癌患者。可测量转移灶的部位包括：肝脏24例、肺14例、中枢神经系统4例、胸膜3例、皮肤6例、胸壁6例、淋巴结8例和骨髓1例。19例患者有两个或更多部位的病变，22例有骨转移。60例患者的反应可评估：ABMT前31例为临床完全缓解（CR），22例部分缓解>50%（PR），7例有新进展。ABMT后，36例患者为CR，16例为PR，1例进展，1例稳定。发生了7例（11.5%）毒性死亡。无造血生长因子情况下血液学恢复的平均时间为32.5天。从治疗开始计算的中位生存期为33±9.4个月，从ABMT日期计算为25.7±4.6个月。从治疗开始计算的中位无事件生存期为20个月，从ABMT计算为13±2个月。中位随访51个月，从初始化疗开始计算的精算生存率为36%，无事件生存率为18%。在对化疗有反应的转移性乳腺癌中，采用CMA和ABMT进行高剂量巩固治疗导致中位生存期为33个月。这些结果为转移性乳腺癌的随机试验评估奠定了基础。
