Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, 1650 Orleans St., Baltimore, MD 21231, USA.
Br J Haematol. 2011 Mar;152(5):593-9. doi: 10.1111/j.1365-2141.2010.08534.x. Epub 2011 Jan 17.
Despite their efficacy in myeloma, corticosteroids have acute and chronic toxicities. Newer agents with significant anti-myeloma activity permit the development of steroid-free regimens. We designed a Phase II clinical trial to study the toxicity and efficacy of a steroid-free combination of bortezomib and thalidomide as a first-line treatment in patients with symptomatic myeloma. Patients received bortezomib 1·3 mg/m(2) on days 1, 4, 8 and 11 every 21 d and thalidomide 150 mg/d for a maximum of eight cycles. Amongst 27 evaluable patients, the overall response was 81·5% with 25·8% near complete response or greater. The response rate was comparable to most other two drug combinations for upfront therapy but lower than that obtained with the use of three drugs. The most common grade 3 toxicities were peripheral neuropathy (22%), pneumonia (15%), fatigue (7%) and anaemia (7%). Peripheral neuropathy completely resolved in 80% of the patients upon completion of therapy, but not in the remaining 20% of patients. No venous thromboembolic events were observed even in the absence of prophylactic anticoagulation. The median progression-free survival was 16·8 months (95% confidence interval 8·7-21·6 months). Median overall survival has not yet been reached at a median follow up of 39 months. The 3-year overall survival was 74%. This study demonstrates: (i) the efficacy of a steroid-free regimen; (ii) mostly reversible treatment-related peripheral neuropathy; and (iii) the absence of venous thrombotic events.
尽管皮质类固醇在骨髓瘤中具有疗效,但它们具有急性和慢性毒性。具有显著抗骨髓瘤活性的新型药物允许开发无类固醇方案。我们设计了一项 II 期临床试验,以研究硼替佐米和沙利度胺无类固醇联合作为有症状骨髓瘤患者一线治疗的毒性和疗效。患者接受硼替佐米 1·3 mg/m(2),每 21 天静脉滴注 1 天、4 天、8 天和 11 天,同时服用沙利度胺 150 mg/d,最多 8 个周期。在 27 名可评估的患者中,总体缓解率为 81.5%,接近完全缓解或更高的缓解率为 25.8%。该缓解率与大多数其他两种药物联合用于一线治疗相当,但低于使用三种药物的缓解率。最常见的 3 级毒性为周围神经病(22%)、肺炎(15%)、疲劳(7%)和贫血(7%)。完成治疗后,80%的患者周围神经病完全缓解,但仍有 20%的患者未缓解。即使没有预防性抗凝,也未观察到静脉血栓栓塞事件。无进展生存的中位时间为 16.8 个月(95%置信区间为 8.7-21.6 个月)。中位随访 39 个月时,中位总生存尚未达到。3 年总生存率为 74%。本研究表明:(i)无类固醇方案的疗效;(ii)主要为可逆转的治疗相关周围神经病;(iii)无静脉血栓栓塞事件。