Goy Andre, Younes Anas, McLaughlin Peter, Pro Barbara, Romaguera Jorge E, Hagemeister Frederick, Fayad Luis, Dang Nam H, Samaniego Felipe, Wang Michael, Broglio Kristine, Samuels Barry, Gilles Frederic, Sarris Andreas H, Hart Susan, Trehu Elizabeth, Schenkein David, Cabanillas Fernando, Rodriguez Alma M
Department of Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 459, Houston, TX 77030, USA.
J Clin Oncol. 2005 Feb 1;23(4):667-75. doi: 10.1200/JCO.2005.03.108. Epub 2004 Dec 21.
Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles.
Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study.
Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.
评估硼替佐米对复发或难治性B细胞非霍奇金淋巴瘤患者的疗效及毒性。
根据临床前数据，患者被分为A组（套细胞淋巴瘤）或B组（其他B细胞淋巴瘤），既往治疗次数不限。硼替佐米每21天在第1、4、8和11天静脉推注给药（1.5mg/m²），最多六个周期。
入组60例患者，既往治疗次数中位数为3.5次（范围为1至12次治疗）；33例患者在A组，27例在B组，包括12例弥漫性大B细胞淋巴瘤、5例滤泡性淋巴瘤（FL）、3例转化型FL、4例小淋巴细胞淋巴瘤（SLL）、2例华氏巨球蛋白血症（WM）和1例边缘区淋巴瘤。在A组中，29例可评估患者中有12例有反应（6例完全缓解[CR]和6例部分缓解[PR]），总缓解率（ORR）为41%（95%CI，24%至61%），进展时间中位数尚未达到，中位随访时间为9.3个月（范围为1.7至24个月）。在B组中，21例可评估患者中有4例有反应（1例SLL患者达到CR，1例FL患者CR未确认，1例弥漫性大B细胞淋巴瘤患者达到PR，1例WM患者达到PR），ORR为19%（95%CI，5%至42%）。3级毒性包括血小板减少（47%）、胃肠道毒性（20%）疲劳（13%）、中性粒细胞减少（10%）和周围神经病变（5%）。4级毒性发生在9例患者（15%）中，3例患者在退出研究后30天内死于疾病进展。
硼替佐米在复发套细胞淋巴瘤中显示出有前景的活性，在其他B细胞淋巴瘤中也有令人鼓舞的结果。未来研究将探索硼替佐米与其他细胞毒性或生物制剂联合应用。
