Department of Hematology and Oncology, Tokai University School of Medicine, Isehara, Japan.
Cancer Sci. 2013 Jul;104(7):912-9. doi: 10.1111/cas.12172. Epub 2013 May 27.
This phase I/II study was conducted to evaluate the safety and efficacy of bortezomib-melphalan-prednisolone in Japanese patients with previously untreated multiple myeloma who are ineligible for hematopoietic stem cell transplantation. One hundred and one patients were enrolled, and 99 patients received up to nine 6-week cycles of bortezomib (0.7/1.0/1.3 mg/m²) on days 1, 4, 8, 11, 22, 25, 29, and 32 in cycles 1-4 and on days 1, 8, 22, and 29 in cycles 5-9, with melphalan (9 mg/m²) and prednisolone (60 mg/m²) on days 1-4 of each cycle. The recommended dose was determined in the phase I portion, and the overall response rate and safety of bortezomib-melphalan-prednisolone at the recommended dose were assessed in the phase II portion. The recommended dose of bortezomib was determined to be 1.3 mg/m². Grade 3 or higher non-hematological adverse events included diarrhea (12%) and peripheral neuropathy (10%); grade 4 hematological adverse events included lymphopenia (41%), neutropenia (30%), and thrombocytopenia (22%). Eleven patients had lung injury associated with bortezomib; two had grade 3 disease, and the other nine had grade 1 or 2 disease. Of the 86 patients treated with 1.3-mg/m² bortezomib in phases I and II, the median number of treatment cycles was 4.5, and the overall response rate was 70% (95% confidence interval: 59-79%). Bortezomib-melphalan-prednisolone with 1.3-mg/m² bortezomib was considered to be tolerable and effective in Japanese patients with previously untreated multiple myeloma. However, further investigation is needed to refine the administration schedule.
这项 I/II 期研究旨在评估硼替佐米-美法仑-泼尼松在不适合造血干细胞移植的初治多发性骨髓瘤日本患者中的安全性和疗效。共纳入 101 例患者，99 例患者接受了多达 9 个 6 周周期的硼替佐米（0.7/1.0/1.3mg/m²）治疗，第 1、4、8、11、22、25、29 和 32 天（第 1-4 周期），第 1、8、22 和 29 天（第 5-9 周期），每个周期的第 1-4 天给予美法仑（9mg/m²）和泼尼松（60mg/m²）。推荐剂量在 I 期部分确定，在 II 期部分评估硼替佐米-美法仑-泼尼松在推荐剂量下的总体反应率和安全性。硼替佐米的推荐剂量确定为 1.3mg/m²。3 级或更高级别的非血液学不良事件包括腹泻（12%）和周围神经病（10%）；4 级血液学不良事件包括淋巴细胞减少症（41%）、中性粒细胞减少症（30%）和血小板减少症（22%）。11 例患者发生与硼替佐米相关的肺损伤；2 例为 3 级疾病，其余 9 例为 1 级或 2 级疾病。在 I 期和 II 期接受 1.3mg/m²硼替佐米治疗的 86 例患者中，中位治疗周期数为 4.5 个，总体缓解率为 70%（95%置信区间：59-79%）。1.3mg/m²硼替佐米联合硼替佐米-美法仑-泼尼松在日本初治多发性骨髓瘤患者中被认为是可耐受且有效的。然而，需要进一步研究来完善给药方案。
