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三氧化二砷、抗坏血酸、异环磷酰胺和泼尼松联合治疗复发难治性多发性骨髓瘤患者的临床活性。

The clinical activity of arsenic trioxide, ascorbic acid, ifosfamide and prednisone combination therapy in patients with relapsed and refractory multiple myeloma.

作者信息

Li Xin, Sun Wan-Jun

机构信息

Department of Hematology and Oncology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People's Republic of China.

Department of Hematology, Second Artillery General Hospital, Beijing, People's Republic of China.

出版信息

Onco Targets Ther. 2015 Apr 9;8:775-81. doi: 10.2147/OTT.S81022. eCollection 2015.

Abstract

This study aimed to investigate the activity of arsenic trioxide (As2O3) combined with ascorbic acid, ifosfamide, and prednisone chemotherapy in patients with repeatedly relapsed and refractory multiple myeloma (MM). Here, we retrospectively analyzed medical data of 30 MM patients showing progressive disease after receiving at least two previous lines of treatment including an immunomodulatory agent (thalidomide or lenalidomide) and a proteasome inhibitor. There were 19 men and eleven women, aged 54-73 (median 65) years, in this study. The distribution of different isotypes included immunoglobulin G(IgG) (12 patients), IgA (six patients), IgD (three), and light chain (nine patients). All the patients were Durie-Salmon stage III and had relapsed at least three times; the median cycles of prior therapies was 15 (range 10-18). The patients were treated with As2O3, ascorbic acid, and CP (ifosfamide 1 g on day 1, day 3, day 5, and day 7; prednisone 30 mg taken orally for 2 weeks). As2O3 was administered as an intravenous infusion at a dose of 10 mg/d and ascorbic acid at a dose of 2 g/d for 14 days of each 4-week cycle. The results showed that after 2 cycles of therapy, there were five patients that attained partial response, 15 had minimal response, five had no change, and five had progressive disease. The overall response rate was 66.7% (20/30 cases), 50% (10/20 cases), and 40% (2/5 cases), respectively, after 2, 4, and 6 cycles of the therapy. But there were no patients that attained complete remission. The median time of overall survival and progression-free survival were 48 (29-120) and 6 (2-8) months, respectively. The most common treatment-related adverse events included neutropenia, fatigue, anemia, thrombocytopenia, and infection that could be tolerated. The results showed that As2O3 combined with ascorbic acid, ifosfamide, and prednisone chemotherapy may be a choice treatment for repeatedly relapsed and refractory MM patients.

摘要

本研究旨在探讨三氧化二砷(As2O3)联合抗坏血酸、异环磷酰胺和泼尼松化疗方案用于多次复发及难治性多发性骨髓瘤(MM)患者的疗效。在此,我们回顾性分析了30例MM患者的医疗数据,这些患者在接受至少两线包括免疫调节剂(沙利度胺或来那度胺)和蛋白酶体抑制剂的既往治疗后出现疾病进展。本研究中有19名男性和11名女性,年龄在54 - 73岁(中位年龄65岁)。不同免疫球蛋白亚型分布包括免疫球蛋白G(IgG)(12例患者)、IgA(6例患者)、IgD(3例)和轻链型(9例患者)。所有患者均为Durie - Salmon III期,且至少复发3次;既往治疗的中位周期数为15(范围10 - 18)。患者接受As2O3、抗坏血酸及CP方案(异环磷酰胺在第1、3、5和7天各1 g;泼尼松30 mg口服2周)治疗。As2O3以10 mg/d的剂量静脉输注,抗坏血酸以2 g/d的剂量给药,每4周周期持续14天。结果显示,治疗2个周期后,有5例患者达到部分缓解,15例患者有微小反应,5例患者病情无变化,5例患者病情进展。治疗2、4和6个周期后的总缓解率分别为66.7%(20/30例)、50%(10/20例)和40%(2/5例)。但无患者达到完全缓解。总生存和无进展生存的中位时间分别为48(29 - 120)个月和6(2 - 8)个月。最常见的治疗相关不良事件包括中性粒细胞减少、乏力、贫血、血小板减少和感染,均可耐受。结果表明,As2O3联合抗坏血酸、异环磷酰胺和泼尼松化疗可能是多次复发及难治性MM患者的一种治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/651c/4399549/79db3834c6dc/ott-8-775Fig1.jpg

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