Tobinai Kensei
Hematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, 104-0045, Tokyo, Japan.
Cancer Chemother Pharmacol. 2003 Jul;52 Suppl 1:S90-6. doi: 10.1007/s00280-003-0595-y. Epub 2003 Jun 18.
Of 12 patients with relapsed CD20(+) B-cell non-Hodgkin's lymphoma (B-NHL) enrolled in a phase I study of rituximab, 11 were eligible, and of these 2 achieved a complete response and 5 a partial response. The elimination half-life of rituximab was 445+/-361 h, and serum rituximab levels were detectable at 3 months. In a phase II study, 90 patients with relapsed indolent B-NHL or mantle cell lymphoma (MCL) were treated with infusions of rituximab 375 mg/m(2) once weekly for four doses. The overall response rate in indolent B-NHL and MCL was 61% (37/61, 95% CI 47-73%) and 46% (6/13, 95% CI 19-75%), respectively. The median progression-free survival (PFS) was shorter in MCL patients, in those with extranodal disease, and in those who had received two or more prior chemotherapy regimens ( P<0.01). Rituximab retreatment was well tolerated in 13 patients with relapsed indolent B-NHL and there were no grade 3/4 nonhematologic toxicities. Partial response was observed in five (38%, 95% CI 14-68%) patients, and the median PFS after retreatment was 5.1 months. In a single-agent phase II study of infusions of rituximab 375 mg/m(2) once weekly for eight doses against relapsed aggressive B-NHL showed, 21 (37%, 95% CI 24-51%) of the 57 eligible patients responded. In conclusion, rituximab is a highly effective agent in relapsed indolent and aggressive B-NHL and MCL with acceptable toxicities. Yttrium-90 provides advantages over iodine-131 because it delivers higher beta energy. In 2002, we initiated a feasibility study of yttrium-90-labeled ibritumomab tiuxetan for relapsed indolent B-NHL in Japan. Gemtuzumab ozogamicin (CMA-676) is a calicheamicin-conjugated humanized anti-CD33 monoclonal antibody. Of 20 patients with relapsed or refractory acute myeloid leukemia enrolled in a "bridging" phase I/II study, 7 showed an objective response. It is concluded that monoclonal antibodies will have play a significant role in the treatment of hematologic malignancies in the future.
在一项利妥昔单抗的I期研究中，入组的12例复发的CD20(+) B细胞非霍奇金淋巴瘤（B-NHL）患者中，11例符合条件，其中2例获得完全缓解，5例获得部分缓解。利妥昔单抗的消除半衰期为445±361小时，3个月时仍可检测到血清利妥昔单抗水平。在一项II期研究中，90例复发的惰性B-NHL或套细胞淋巴瘤（MCL）患者接受利妥昔单抗375 mg/m²静脉输注，每周1次，共4剂。惰性B-NHL和MCL的总缓解率分别为61%（37/61，95%CI 47-73%）和46%（6/13，95%CI 19-75%）。MCL患者、有结外病变的患者以及接受过两种或更多先前化疗方案的患者的无进展生存期（PFS）中位数较短（P<0.01）。13例复发的惰性B-NHL患者再次接受利妥昔单抗治疗耐受性良好，未出现3/4级非血液学毒性。5例（38%，95%CI 14-68%）患者观察到部分缓解，再次治疗后的PFS中位数为5.1个月。在一项针对复发侵袭性B-NHL的单药II期研究中，57例符合条件的患者中，21例（37%，95%CI 24-51%）有反应。总之，利妥昔单抗是复发的惰性和侵袭性B-NHL及MCL的高效药物，毒性可接受。钇-90比碘-131更具优势，因为它能释放更高的β能量。2002年，我们在日本启动了一项针对复发惰性B-NHL的钇-90标记替伊莫单抗的可行性研究。吉妥单抗奥唑米星（CMA-676）是一种与卡奇霉素偶联的人源化抗CD33单克隆抗体。在一项 “桥接 ”I/II期研究中入组的20例复发或难治性急性髓性白血病患者中，7例有客观反应。结论是单克隆抗体在未来血液系统恶性肿瘤的治疗中将发挥重要作用。
