美法仑和泼尼松联合长春新碱、卡莫司汀、美法仑、环磷酰胺及泼尼松治疗多发性骨髓瘤的比较：东部肿瘤协作组E2479研究结果

Comparison of melphalan and prednisone with vincristine, carmustine, melphalan, cyclophosphamide, and prednisone in the treatment of multiple myeloma: results of Eastern Cooperative Oncology Group Study E2479.

作者信息

Oken M M, Harrington D P, Abramson N, Kyle R A, Knospe W, Glick J H

机构信息

The Virginia Piper Cancer Institute and the University of Minnesota, Minneapolis 55407, USA.

出版信息

Cancer. 1997 Apr 15;79(8):1561-7.

PMID:9118039

Abstract

BACKGROUND

The Eastern Cooperative Oncology Group (ECOG) performed a Phase III comparison of melphalan and prednisone (MP) with vincristine, carmustine (BCNU), melphalan, cyclophosphamide, and prednisone (VBMCP) in an attempt to determine which of these regimens should be the standard treatment for multiple myeloma.

METHODS

Four hundred seventy-nine previously untreated patients with multiple myeloma from 23 ECOG institutions were enrolled. Treatment, assigned by randomization, consisted of either 4-week cycles of MP or 5-week cycles of VBCMP. After 1 year of induction therapy, patients received MP or VBMCP maintenance therapy at 6- and 8- week intervals, respectively, until relapse. Patients who experienced treatment failure with MP were eligible for crossover therapy with VBMCP.

RESULTS

Objective responses were obtained for 51% of patients receiving MP, as compared with 72% of patients receiving VBMCP (P < 0.001). Response duration was also longer with VBMCP (median, 18 months with MP vs. 24 months with VBMCP; P = 0.007). Overall survival was not significantly different between MP and VBMCP (P = 0.30). The 5-year survival for VBMCP was 26%, as compared with 19% for MP. VBMCP was associated with more nausea, peripheral nerve toxicity, alopecia, and neutropenia, but the infection rate was equal to that observed with MP. Both regimens were generally well tolerated. The main exception was that elderly patients who were confined to bed had a higher risk of death with VBMCP. The two regimens produced a similar incidence of late secondary myelodysplastic syndrome and acute leukemia. Crossover VBMCP for patients failing with MP was only minimally effective, with an objective response rate of 20% and median survival of 11 months after crossover.

CONCLUSIONS

VBMCP is more effective than MP in producing and sustaining remission of multiple myeloma. It is associated with a marginal survival advantage and an apparently greater chance of surviving 5 years for patients who can tolerate moderately intensive combination chemotherapy. Cancer 1997;79:1561-7. 1997 American Cancer Society.

摘要

背景

东部肿瘤协作组（ECOG）对美法仑和泼尼松（MP）与长春新碱、卡莫司汀（BCNU）、美法仑、环磷酰胺和泼尼松（VBMCP）进行了一项III期比较研究，试图确定这些方案中哪一种应作为多发性骨髓瘤的标准治疗方案。

方法

招募了来自23个ECOG机构的479例既往未接受过治疗的多发性骨髓瘤患者。通过随机分组进行治疗，治疗方案包括4周疗程的MP或5周疗程的VBCMP。诱导治疗1年后，患者分别每6周和8周接受MP或VBMCP维持治疗，直至复发。接受MP治疗失败的患者有资格接受VBMCP交叉治疗。

结果

接受MP治疗的患者中51%获得了客观缓解，而接受VBMCP治疗的患者中这一比例为72%（P<0.001）。VBMCP的缓解持续时间也更长（MP组中位缓解持续时间为18个月，VBMCP组为24个月；P=0.007）。MP和VBMCP的总生存期无显著差异（P=0.30）。VBMCP的5年生存率为26%，而MP为19%。VBMCP与更多的恶心、外周神经毒性、脱发和中性粒细胞减少相关，但感染率与MP组观察到的相同。两种方案总体耐受性良好。主要例外是卧床的老年患者接受VBMCP治疗时死亡风险更高。两种方案导致晚期继发性骨髓增生异常综合征和急性白血病的发生率相似。MP治疗失败的患者接受VBMCP交叉治疗的效果甚微，交叉治疗后的客观缓解率为20%，中位生存期为11个月。