Oncotherapeutics, James R. Berenson, MD, Inc. Institute for Myeloma and Bone Cancer Research, 9201 W. Sunset Blvd., West Hollywood, CA 90069, USA.
Br J Haematol. 2011 Dec;155(5):580-7. doi: 10.1111/j.1365-2141.2011.08884.x. Epub 2011 Sep 26.
The combination of pegylated liposomal doxorubicin (PLD), bortezomib and dexamethasone has shown efficacy in the treatment of multiple myeloma (MM) patients. Our earlier retrospective study suggested that modification of the doses, schedules and route of administration of these drugs appears to reduce toxicity without compromising anti-MM activity. As a result, we evaluated this modified drug combination in the frontline setting in a prospective multicentre phase II trial. Thirty-five previously untreated MM patients were enrolled. Dexamethasone IV 40 mg, bortezomib 1 mg/m(2) and PLD 5 mg/m(2) were administered on days 1, 4, 8 and 11 of a 4-week cycle. Patients were treated to their maximum response plus two additional cycles. The treatment regimen was discontinued after a maximum of eight cycles. Our modified schedule and dosing regimen achieved a high overall response rate of 86%, while showing a marked decrease in the incidence and severity of peripheral neuropathy, palmar-plantar erythrodysesthesia and myelosuppression compared to the standard dosing on a 3-week cycle using these drugs. This modified regimen of dexamethasone, bortezomib and PLD shows improved tolerability and safety while maintaining a high response rate when compared to standard treatment with these agents in the frontline setting.
多柔比星脂质体注射液(PLD)、硼替佐米和地塞米松联合治疗多发性骨髓瘤(MM)患者显示出疗效。我们之前的回顾性研究表明,这些药物的剂量、方案和给药途径的改变似乎可以降低毒性,而不影响抗 MM 活性。因此,我们在一项前瞻性多中心 II 期试验中在前线环境中评估了这种改良的药物联合治疗。共纳入 35 例未经治疗的 MM 患者。地塞米松 IV 40 mg,硼替佐米 1 mg/m(2)和 PLD 5 mg/m(2)于每 4 周周期的第 1、4、8 和 11 天给药。患者接受最多 2 个额外周期的治疗。最多 8 个周期后停止治疗方案。我们的改良方案和剂量方案达到了 86%的总缓解率,同时与使用这些药物在 3 周周期的标准剂量相比,外周神经病变、手掌-足底红斑感觉异常和骨髓抑制的发生率和严重程度显著降低。与这些药物在前线治疗中的标准治疗相比,地塞米松、硼替佐米和 PLD 的这种改良方案具有更好的耐受性和安全性,同时保持高缓解率。