Weaver C H, Zhen B, Schwartzberg L S, Leff R, Magee M, Geier L, Deaton K, Lewkow L, Buckner C D
Clinical Research Division of Response Oncology, Inc., Memphis, TN, USA.
Bone Marrow Transplant. 1998 Aug;22(3):245-51. doi: 10.1038/sj.bmt.1701324.
This study was designed to determine the maximum tolerated dose (MTD) of high-dose melphalan (HDM), with peripheral blood stem cell support, that could be given twice within 90 days to patients with multiple myeloma. Twenty patients received tandem HDM at 160, 180 or 200 mg/m2 and a total of 55 were treated at the estimated MTD of 200 mg/m2. Seventeen of 55 (31%) did not receive cycle 2; six because of low CD34+ cell yields, three because of severe (n = 1) or fatal toxicities (n = 2) and eight for other reasons. The median interval between doses for 38 patients was 70 days (range 41-225). Three of 55 patients (5%) died of treatment-related causes. In patients completing two cycles of HDM, at any dose level, the complete remission rate improved from 15% following cycle 1 to 55% following cycle 2. The probabilities of survival, event-free survival and relapse or progression at 18 months for the 55 patients treated at the MTD were 0.84, 0.76 and 0.20, respectively, with a median follow-up of 19 months (range 9-36) from mobilization chemotherapy. It was concluded that two cycles of HDM, 200 mg/m2, could be administered to approximately 70% of patients under the age of 66 with multiple myeloma in a median interval of 70 days, with improvement in CR rates.
本研究旨在确定在接受外周血干细胞支持的情况下，大剂量美法仑（HDM）在90天内可对多发性骨髓瘤患者进行两次给药的最大耐受剂量（MTD）。20例患者接受了160、180或200mg/m²的串联HDM治疗，共有55例患者接受了估计MTD为200mg/m²的治疗。55例患者中有17例（31%）未接受第2周期治疗；6例因CD34+细胞产量低，3例因严重毒性（n = 1）或致命毒性（n = 2），8例因其他原因。38例患者两次给药之间的中位间隔为70天（范围41 - 225天）。55例患者中有三例（5%）死于治疗相关原因。在完成两个周期HDM治疗的患者中，无论剂量水平如何，完全缓解率从第1周期后的15%提高到第2周期后的55%。在MTD剂量下接受治疗的55例患者在18个月时的生存率、无事件生存率和复发或进展概率分别为0.84、0.76和0.20，自动员化疗起的中位随访时间为19个月（范围9 - 36个月）。得出的结论是，对于年龄在66岁以下的多发性骨髓瘤患者，约70%可在中位间隔70天的情况下接受两个周期200mg/m²的HDM治疗，且完全缓解率有所提高。
