Romano Alessandra, Chiarenza Annalisa, Conticello Concetta, Cavalli Maide, Vetro Calogero, Di Raimondo Cosimo, Cunsolo Rosario, Palumbo Giuseppe Alberto, Di Raimondo Francesco
Department of Clinical and Molecular Biomedicine, Section of Haematology, University of Catania, Catania, Italy; Division of Hematology, Azienda Policlinico-OVE, Catania, Italy; Fondazione Umberto Veronesi, Rome, Italy.
Eur J Haematol. 2014 Sep;93(3):207-13. doi: 10.1111/ejh.12325. Epub 2014 Apr 18.
In vitro studies have shown synergistic anti-myeloma effects of bortezomib combined with alkylating agents or anthracycline. We tested safety and efficacy of the combination of bortezomib, doxorubicin cyclophosphamide, and dexamethasone (ABCD) in the treatment of relapsed/refractory myeloma.
ABCD consisted of bortezomib given intravenous (IV) at dosage 1.3 mg/m(2) , dexamethasone 40 mg IV on days 1, 4, 8, and 15, pegylated liposomal doxorubicin (PLD) 20 mg IV on days 1 and 15, plus cyclophosphamide 100 mg/d per os for 15 d. Between January 2008 and February 2009, 24 patients received a median of four 28-d ABCD cycles (range 1-6). All patients had been already treated with a median of two previous lines of treatment (range 1-6): 38% were resistant to previous therapies and 62% were relapsed.
Clinical response was observed in 12 patients (50%), including 29% of very good partial remissions or better. Side effects included hematological toxicity (31% any grade), grades 3-4 thrombocytopenia (9%), grades 3-4 anemia (17%). Non-hematological toxicity affected 32% of administered cycles and included gastrointestinal disturbances (54%), peripheral neuropathy (8%), and infections (8%). After a median follow-up of 21.5 months (range 2-44 months), median of progression-free survival (PFS) was 8.7 months and median overall survival was 22.5 months. Achieving at least partial response within the second cycle was associated with a better PFS (19.5 months vs. 3.5 months), P = 0.03, HR 0.35 (CI 95% 0.13-0.90).
ABCD is safe and effective for relapsed/refractory MM subjects previously treated with novel agents.
体外研究显示硼替佐米与烷化剂或蒽环类药物联合具有协同抗骨髓瘤作用。我们测试了硼替佐米、阿霉素、环磷酰胺和地塞米松（ABCD方案）联合治疗复发/难治性骨髓瘤的安全性和疗效。
ABCD方案包括静脉注射剂量为1.3mg/m²的硼替佐米，第1、4、8和15天静脉注射40mg地塞米松，第1和15天静脉注射20mg聚乙二醇化脂质体阿霉素（PLD），加口服环磷酰胺100mg/d，共15天。2008年1月至2009年2月，24例患者接受了中位4个28天的ABCD周期治疗（范围1 - 6个周期）。所有患者此前已接受中位2线治疗（范围1 - 6线）：38%对先前治疗耐药，62%复发。
12例患者（50%）观察到临床反应，包括29%达到非常好的部分缓解或更好。副作用包括血液学毒性（31%为任何级别）、3 - 4级血小板减少（9%）、3 - 4级贫血（17%）。非血液学毒性影响32%的给药周期，包括胃肠道紊乱（54%）、周围神经病变（8%）和感染（8%）。中位随访21.5个月（范围2 - 44个月），无进展生存期（PFS）中位数为8.7个月，总生存期中位数为22.5个月。在第二个周期内达到至少部分缓解与更好的PFS相关（19.5个月对3.5个月），P = 0.03，风险比0.35（95%置信区间0.13 - 0.90）。
ABCD方案对于先前接受过新型药物治疗的复发/难治性骨髓瘤患者是安全有效的。
