Background: Bortezomib (B), known as Velcade, is a reversible proteasome inhibitor approved for relapsed/refractory multiple myeloma (RRMM) patients (pts). The standard of care protocol includes eight cycles of intravenous push (IVP) injections of B and oral dexamethasone (D), which increases the toxicity. Here, we describe the results of an open-label, phase II clinical trial employing only four cycles of B/D. Methods: RRMM pts treated with at least one previous therapy qualified for the trial. Pts were treated with B 1.3 mg/m2IVP or subcutaneous (SC) on day 1, 4, 8, and 11, followed by a 10-day rest, Q21 days for four cycles; followed by maintenance therapy with once weekly B 1.6 mg/m2IVP or SC on day 1, 8, 15, and 22, followed by 13 days’ rest, repeated Q36 day. Pts received D 20 mg on the days of and days after B. Pts with a complete response (CR) were removed. Those with a partial response (PR) or stable disease (SD) were placed on maintenance therapy until progressive disease (PD), unacceptable toxicity, or pts’ decision to stop. Results: A total of 24 pts were enrolled. CR was observed in six pts (25%), PR in eight pts (33%), and SD in nine pts (37.5%). Moreover, 14 of the 24 pts (58.3%) had PR or better. Four pts had PD during induction. The grade 3 toxicities included fatigue (58%), sensory neuropathy (54%), and thrombocytopenia (50%); the grade 4 toxicities were thrombocytopenia (12.5%), fatigue (12.5%), and sensory neuropathy (12.5%). Conclusions: A short course of B/D, plus maintenance with B, is well tolerated in RRMM pts. Long-term maintenance with B/D could become an alternative to new agents.
背景：硼替佐米（Bortezomib，商品名万珂）是一种可逆性蛋白酶体抑制剂，已获批用于治疗复发/难治性多发性骨髓瘤患者。标准治疗方案包含八个周期的硼替佐米静脉推注联合口服地塞米松治疗，但该方案会增加毒性反应。本研究报道一项采用仅四个周期硼替佐米/地塞米松治疗的开放标签II期临床试验结果。方法：本研究纳入至少接受过一线治疗的复发/难治性多发性骨髓瘤患者。诱导期治疗方案为：第1、4、8、11天接受硼替佐米1.3 mg/m²静脉推注或皮下注射，随后停药10天，每21天为一个周期，共进行四个周期；随后进入维持治疗阶段：第1、8、15、22天接受每周一次的硼替佐米1.6 mg/m²静脉推注或皮下注射，随后停药13天，每36天重复一次。患者在硼替佐米给药当日及次日联合口服地塞米松20 mg。达到完全缓解的患者退出研究，达到部分缓解或疾病稳定的患者继续接受维持治疗，直至疾病进展、出现不可耐受的毒性反应或患者主动要求终止治疗。结果：共纳入24例患者。完全缓解6例（25%），部分缓解8例（33%），疾病稳定9例（37.5%）。此外，24例患者中14例（58.3%）达到部分缓解及以上疗效。4例患者在诱导期出现疾病进展。3级毒性反应包括疲劳（58%）、感觉神经病变（54%）和血小板减少（50%）；4级毒性反应为血小板减少（12.5%）、疲劳（12.5%）和感觉神经病变（12.5%）。结论：短期硼替佐米/地塞米松方案联合硼替佐米维持治疗在复发/难治性多发性骨髓瘤患者中耐受性良好。硼替佐米/地塞米松长期维持治疗可能成为新型药物的替代方案。
肿瘤(癌症)患者之家