Richardson Paul G, Sonneveld Pieter, Schuster Michael W, Stadtmauer Edward A, Facon Thierry, Harousseau Jean-Luc, Ben-Yehuda Dina, Lonial Sagar, Goldschmidt Hartmut, Reece Donna, Bladé Joan, Boccadoro Mario, Cavenagh Jamie D, Boral Anthony L, Esseltine Dixie-Lee, Wen Patrick Y, Amato Anthony A, Anderson Kenneth C, San Miguel Jesus
Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Br J Haematol. 2009 Mar;144(6):895-903. doi: 10.1111/j.1365-2141.2008.07573.x. Epub 2009 Jan 16.
The frequency, characteristics and reversibility of bortezomib-associated peripheral neuropathy were evaluated in the phase III APEX (Assessment of Proteasome Inhibition for Extending Remissions) trial in patients with relapsed myeloma, and the impact of a dose-modification guideline on peripheral neuropathy severity and reversibility was assessed. Patients received bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11, eight 21-d cycles, then days 1, 8, 15, 22, three 35-d cycles); bortezomib was held, dose-reduced or discontinued depending on peripheral neuropathy severity, according to a protocol-specified dose-modification guideline. Overall, 124/331 patients (37%) had treatment-emergent peripheral neuropathy, including 30 (9%) with grade >or=3; incidence and severity were not affected by age, number/type of prior therapies, baseline glycosylated haemoglobin level, or diabetes history. Grade >or=3 incidence appeared lower versus phase II trials (13%) that did not specifically provide dose-modification guidelines. Of patients with grade >or=2 peripheral neuropathy, 58/91 (64%) experienced improvement or resolution to baseline at a median of 110 d, including 49/72 (68%) who had dose modification versus 9/19 (47%) who did not. Efficacy did not appear adversely affected by dose modification for grade >or=2 peripheral neuropathy. Bortezomib-associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma. Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome.
在一项针对复发骨髓瘤患者的III期APEX（蛋白酶体抑制作用延长缓解期评估）试验中，评估了硼替佐米相关周围神经病变的发生率、特征及可逆性，并评估了剂量调整指南对周围神经病变严重程度及可逆性的影响。患者接受硼替佐米1.3 mg/m²（第1、4、8、11天，共8个21天周期，之后为第1、8、15、22天，共3个35天周期）；根据方案规定的剂量调整指南，根据周围神经病变的严重程度，停用、降低剂量或中断硼替佐米治疗。总体而言，124/331例患者（37%）出现治疗中出现的周围神经病变，其中30例（9%）为≥3级；发病率和严重程度不受年龄、既往治疗的次数/类型、基线糖化血红蛋白水平或糖尿病史的影响。与未专门提供剂量调整指南的II期试验（13%）相比，≥3级发病率似乎较低。在≥2级周围神经病变的患者中，58/91例（64%）在中位110天时病情改善或恢复至基线水平，其中49/72例（68%）进行了剂量调整，而未进行剂量调整的患者为9/19例（47%）。≥2级周围神经病变的剂量调整似乎未对疗效产生不利影响。硼替佐米相关周围神经病变在大多数复发骨髓瘤患者中是可控制且可逆的。使用特定指南进行剂量调整可改善周围神经病变的管理，且不会对疗效产生不利影响。
