Ayash L J, Elias A, Schwartz G, Wheeler C, Ibrahim J, Teicher B A, Reich E, Warren D, Lynch C, Richardson P, Schnipper L, Frei E, Antman K
Department of Cancer Pharmacology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
J Clin Oncol. 1996 Nov;14(11):2984-92. doi: 10.1200/JCO.1996.14.11.2984.
Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration.
Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support.
Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively.
Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.
在接受环磷酰胺（6000mg/m²）、噻替派（500mg/m²）和卡铂（800mg/m²）（CTCb）强化治疗周期及自体骨髓移植（ABMT）后，21%的转移性乳腺癌患者在中位50个月时仍无疾病进展。本试验研究了大剂量美法仑序贯CTCb是否能改善疾病反应及持续时间。
对诱导治疗至少有部分反应（PRS）的女性患者给予美法仑（140或180mg/m²），并给予外周血祖细胞（PBPC）和粒细胞集落刺激因子（G-CSF）支持。对她们作为门诊患者进行监测。恢复后，患者住院接受CTCb治疗，并给予骨髓、PBPC和G-CSF支持。
检查了67名女性的数据，距CTCb治疗的中位时间为25个月。使用美法仑后，49名（73%）患者因发热（89%）、粘膜炎（35%）或感染（15%）需要住院（中位住院时间为8天）。所有患者均接受了CTCb治疗。对于前33名患者，从开始使用美法仑到进行CTCb的中位天数为24天。在CTCb治疗期间，11名患者出现肝毒性（1例死于肝静脉闭塞病[VOD]）后，强化治疗之间的间隔延长至35天，未再出现问题。23名患者（34%）在CTCb治疗后中位16个月时无疾病进展。整个组的中位无进展生存期（PFS）和生存时间分别估计为11个月和20个月。
与单次强化CTCb相比，大剂量美法仑序贯CTCb治疗至今未产生更优的PFS。本报告讨论了与患者选择、诱导耐药的作用以及可能对结果产生不利影响的烷化剂给药方案相关的因素。
