Berenson James R, Matous Jeffrey, Swift Regina A, Mapes Russell, Morrison Blake, Yeh Howard S
Institute for Myeloma and Bone Cancer Research and Oncotherapeutics Inc, West Hollywood, CA 90069, USA.
Clin Cancer Res. 2007 Mar 15;13(6):1762-8. doi: 10.1158/1078-0432.CCR-06-1812.
This multicenter, open-label, phase I/II dose escalation study assessed the safety/tolerability and initial efficacy of arsenic trioxide/bortezomib/ascorbic acid (ABC) combination therapy in patients with relapsed/refractory multiple myeloma.
Enrolled in six cohorts, patients were given arsenic trioxide (0.125 or 0.250 mg/kg), bortezomib (0.7, 1.0, or 1.3 mg/m(2)), and a fixed dose of ascorbic acid (1 g) i.v. on days 1, 4, 8, and 11 of a 21-day cycle for a maximum of eight cycles. The primary end point was safety/tolerability of the ABC regimen.
Twenty-two patients (median age, 63 years) were enrolled, having failed a median of 4 (range, 3-9) prior therapies. One occurrence of grade 4 thrombocytopenia was observed. One patient had asymptomatic arrhythmia and withdrew from the study. Objective responses were observed in 6 (27%) patients, including two partial responses and four minor responses. Median progression-free survival was 5 months (95% confidence interval, 2-9 months), and median overall survival had not been reached. The 12-month progression-free survival and overall survival rates were 34% and 74%, respectively. One (minor response) of six patients receiving the lowest dose of bortezomib (0.7 mg/m(2)) and 5 (2 partial responses and 3 minor responses) of 16 patients receiving the higher doses (1.0 or 1.3 mg/m(2)) responded.
The ABC regimen was well tolerated by most patients, and it produced preliminary signs of efficacy with an objective response rate of 27% in this heavily pretreated study population. These findings warrant further clinical evaluation of the ABC combination for treatment of relapsed/refractory multiple myeloma.
本多中心、开放标签的I/II期剂量递增研究评估了三氧化二砷/硼替佐米/抗坏血酸（ABC）联合疗法在复发/难治性多发性骨髓瘤患者中的安全性/耐受性及初始疗效。
患者入组六个队列，在21天周期的第1、4、8和11天静脉注射三氧化二砷（0.125或0.250 mg/kg）、硼替佐米（0.7、1.0或1.3 mg/m²）以及固定剂量的抗坏血酸（1 g），最多进行八个周期。主要终点是ABC方案的安全性/耐受性。
共纳入22例患者（中位年龄63岁），之前的治疗方案中位数为4种（范围3 - 9种），均治疗失败。观察到1例4级血小板减少症。1例患者出现无症状性心律失常并退出研究。6例（27%）患者观察到客观缓解，包括2例部分缓解和4例微小缓解。中位无进展生存期为5个月（95%置信区间，2 - 9个月），中位总生存期尚未达到。12个月无进展生存率和总生存率分别为34%和74%。接受最低剂量硼替佐米（0.7 mg/m²）的6例患者中有1例（微小缓解）有反应，接受较高剂量（1.0或1.3 mg/m²）的16例患者中有5例（2例部分缓解和3例微小缓解）有反应。
ABC方案在大多数患者中耐受性良好，在这个经过大量预处理的研究人群中产生了初步疗效迹象，客观缓解率为27%。这些发现值得对ABC联合疗法治疗复发/难治性多发性骨髓瘤进行进一步临床评估。
