Popat Rakesh, Oakervee Heather, Williams Catherine, Cook Mark, Craddock Charles, Basu Supratik, Singer Charles, Harding Stephen, Foot Nicola, Hallam Simon, Odeh Liz, Joel Simon, Cavenagh Jamie
Department of Haematology, St. Bartholomew's Hospital, London, UK.
Br J Haematol. 2009 Mar;144(6):887-94. doi: 10.1111/j.1365-2141.2008.07572.x. Epub 2009 Jan 12.
This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2.5-10.0 mg/m(2)) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7.5 mg/m(2) and bortezomib 1.3 mg/m(2). The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD (n = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD (P < 0.05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.
这项多中心I/II期研究调查了低剂量静脉注射美法仑联合硼替佐米对复发多发性骨髓瘤（MM）患者的最大耐受剂量（MTD）、安全性和疗效。患者在28天周期的第1、4、8和11天接受硼替佐米1.3mg/m²，在第2天接受递增剂量的静脉注射美法仑（2.5 - 10.0mg/m²），最多8个周期。对于病情进展或稳定的患者添加20mg地塞米松。共纳入53例患者。MTD定义为美法仑7.5mg/m²和硼替佐米1.3mg/m²。总缓解率（ORR）为68%（23%完全或接近完全缓解[CR/nCR]），而在MTD组（n = 33）中ORR为76%（34% CR/nCR）。中位随访17个月后，无进展生存期的中位数为10个月，在MTD组升至12个月（与非MTD方案相比，P < 0.05）。总生存期的中位数为28个月，但在MTD组尚未达到。3/4级不良事件包括血小板减少（62%）、中性粒细胞减少（57%）、感染（21%）和神经病变（15%）。硼替佐米和低剂量静脉注射美法仑联合治疗对复发MM患者是一种安全且高效的方案。这些数据表明该联合方案值得进一步研究。
