含沙利度胺的联合化疗方案与沙利度胺单药对复发难治多发性骨髓瘤的疗效比较

Cyclophosphamide thalidomide and dexamethasone combination chemotherapy in comparision with single-agent thalidomide in relapsed and refractory multiple myloma

目的观察沙利度胺、环磷酰胺、地塞米松(CTD)联合化疗在复发、难治多发性骨髓瘤(multiple myeloma,MM)中的疗效及副反应,并同沙利度胺单药进行对比。方法对2006年4月至2009年3月中山大学附属第一医院14例复发、难治MM患者给予CTD方案化疗,每4周为1个疗程。以26例接受沙利度胺单药治疗的复发、难治MM患者作为历史对照。所有患者接受中位3个疗程(1～20个疗程)的化疗。采用EBMT疗效评价标准评价疗效,按国立癌症研究所的常规毒性判定标准评价不良反应。结果CTD组总反应率66.7%,其中接近完全缓解(nCR)2例(16.7%),部分缓解(PR)2例(16.7%),轻微反应(MR)4例(33.3%),无变化(NC)4例(33.3%),中位显效疗程数为2个疗程,达最佳疗效中位疗程数为3个疗程。CTD做为二线治疗的疗效和缓解程度要高于三线治疗的患者。与沙利度胺单药的疗效相比,虽然总反应率无统计学意义,但CTD组缓解程度要高于沙利度胺单药,后者无一例患者达nCR。CTD方案的毒副反应轻微,表现为Ⅰ～Ⅱ级的白细胞减少(42.8%)、血小板减少(21.4%)、嗜睡(35.7%)、腹胀便秘(35.7%)等,经对症处理后可缓解,同沙利度胺单药相比并未增加其毒副反应。结论CTD方案对于复发、难治MM患者具有较好的疗效,且用药方便,副反应轻微,可门诊给药。

Objective This study was designed to compare the efficacy of thalidomide-based combination regimen（cyelo- phosphamide,thalidomide and dexamethasone） with that of thalidomide as a single agent in retapsed/refractory multiple myeloma（MM） ,and analyze their toxicities. Methods Twenty-six patients who had received thalidomide regimen were taken as a historical control group, 14 cases with replapsed/refractory multiple myeloma were treated with CTD regimen in a 28-day cycle. The patients received a median of 3 cycles（ range, 1 -20 cycles） of the treatment. Response to CTD was evaluated according to the criteria of European Group for Blood and Marrow Transplantation（EBMT） ;adverse events were graded according to the National Cancer Institute Common Toxicity Criteria. Results Overall response rates were 66. 7% in cases with CTD. 2 cases obtained near complete remission （nCR）, 2 had partial remission （PR）, 4 had minimal response （MR） and 2 were of no change （NC）. CTD had higher efficacy and remission degree as second-line therapy compared with third-line therapy. The median initial effective time was 2 cycles and the median optimal efficacy time was 3 cycles. There was no significant difference in overall response rate between CTD and single-agent thalidomide. However, nCR occurred in 2 cases with CTD and no nCR was observed in single-agent thalidomide. Grade Ⅰ - Ⅱ adverse events, including leucocytopenia （ 42. 8% ）, thrombocytopenia （ 21.4% ）, somnolence （ 35.7 % ）, abdominal distention and constipation（35. 7% ） could be relieved by symptomatic treatment not influencing chemotherapy regimen. Conclusion CTD regimen was an effective and safe method in treating relapsed/refractory MM. CTD regimen was used conveniently and not expensive. It can be even applied in outpatient.