Sidana Surbhi, Narkhede Mayur, Elson Paul, Hastings Debbie, Faiman Beth, Valent Jason, Samaras Christy, Hamilton Kimberly, Liu Hien K, Smith Mitchell R, Reu Frederic J
Department of Internal Medicine, Cleveland Clinic, Cleveland, Ohio, United States of America.
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, United States of America.
PLoS One. 2017 Mar 9;12(3):e0172996. doi: 10.1371/journal.pone.0172996. eCollection 2017.
Randomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.
Comprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.
Fifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26-4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58-2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001).
Weekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.
随机研究表明，与最初的标准每周两次静脉给药方案相比，硼替佐米（BTZ）可以每周一次静脉给药或每周两次皮下给药，神经病变风险更低且抗骨髓瘤疗效未降低。因此，每周一次皮下给药应产生最佳治疗指数且被广泛使用，但在临床试验背景下尚未与既定给药方案进行比较。
对2010年12月我们改为每周皮下给药之前或之后接受首个含BTZ方案治疗骨髓瘤或AL淀粉样变性的344例连续患者的疾病控制和神经病变症状进行了全面的电子病历回顾。进行了单变量和多变量分析，对年龄、基础疾病、同时使用的抗癌药物、易患神经病变的基础状况以及既往方案数量进行了调整，将每周皮下给药与其他方案进行比较。
53例患者每周接受皮下BTZ给药，17例每周皮下给药两次，127例每周静脉给药，147例每周静脉给药两次。与每周皮下给药相比，其他方案的任何级别的神经病变风险更高（44.3%对26.9%，p = 0.001），而缓解率相似（分别为72.1%对76.6%，p = 0.15）。多变量分析支持更高的神经病变风险（优势比2.45，95%置信区间1.26 - 4.76，p = 0.008），而与每周皮下给药相比，其他方案未达到缓解（=部分缓解或更好）的可能性相当（优势比1.25，95%置信区间0.58 - 2.71，p = 0.56）。当开始每周皮下给药BTZ时，较低的神经病变风险转化为更长的治疗持续时间（p = 0.001）。
每周皮下注射BTZ的活性与其他方案相当，且神经病变发生率低。
