An open-label phase I/II study of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed myeloma
An open-label phase I/II study of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed myeloma
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DOI：
10.1111/ejh.12509
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发表时间：
2015-11-01
影响因子：
3.1
通讯作者：
Alsina, Melissa
中科院分区：
文献类型：
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作者：
Nishihori, Taiga;Baz, Rachid;Alsina, Melissa
我们进行了一项1/2期试验，评估环磷酰胺、硼替佐米、聚乙二醇化脂质体阿霉素和地塞米松（CVDD）联合治疗新诊断的多发性骨髓瘤（MM）。1期研究的主要目的是评价最大计划剂量（MPD）的安全性和耐受性，2期研究的主要目的是评估总体缓解率。患者接受4个剂量水平的6-8个周期的CVDD治疗。无剂量限制性毒性。MPD为环磷酰胺750 mg/m2，第1天静脉注射，硼替佐米1.3mg/m2，第1、4、8、11天静脉注射，多柔比星脂质体30 mg/m2，第4天静脉注射，地塞米松20 mg，硼替佐米当天及之后口服（21天为一周期）。49例患者在MPD接受治疗，其中22%患有高风险骨髓瘤。最常见的3级毒性包括骨髓抑制、感染和疲劳。标准风险队列的总缓解率和完全缓解率分别为91%和26%，高危队列分别为100%和58%。中位随访34个月后，中位无进展生存期为31.3个月。标准风险组和高危组的2年总生存率分别为91.1%和88.9%。CVDD方案耐受性好，对新诊断MM有较高的疗效。
We conducted a phase 1/2 trial evaluating the combination of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly diagnosed multiple myeloma (MM). The primary objective of the phase 1 was to evaluate the safety and tolerability of maximum planned dose (MPD) and the phase 2 was to assess the overall response rate. Patients received 6-8 cycles of CVDD at four dose levels. There were no dose-limiting toxicities. The MPD was cyclophosphamide 750mg/m(2) IV on day 1, bortezomib 1.3mg/m(2) IV on days 1, 4, 8, 11, pegylated liposomal doxorubicin 30mg/m(2) IV on day 4, and dexamethasone 20mg orally on the day of and after bortezomib (21-d cycle). Forty-nine patients were treated at the MPD of which 22% had high-risk myeloma. The most common grade 3 toxicities included myelosuppression, infection, and fatigue. Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively. After a median follow-up of 34months, the median progression-free survival was 31.3months. The 2-yr overall survival was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively. CVDD regimen was well tolerated and was highly active in newly diagnosed MM.