Keating M, O'Brien S
Department of Leukemia, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Semin Oncol. 2000 Dec;27(6 Suppl 12):86-90.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a chimeric monoclonal antibody that targets mature B cells in most lymphoid B-cell malignancies. Rituximab is approved by the US Food and Drug Administration for therapy for recurrent B-cell lymphoma. In initial clinical trials the activity in small lymphocytic lymphoma, the counterpart of chronic lymphocytic leukemia (CLL), was less than 20%. In an attempt to increase the level of rituximab activity in CLL, we conducted a phase I dose-escalation study to overcome both the lower CD20 antigen density on CLL cells compared with lymphoma cells and the shorter half-life of rituximab in small lymphocytic lymphoma. Cohorts of patients were treated with escalated doses on weeks 2, 3, and 4 after an initial rituximab dose of 375 mg/m2 on day 1. The maximum dose of rituximab evaluated was 2,250 mg/m2. There is clear evidence of a dose-response relationship. Severe toxicity (grades 3 and 4) noted following the first dose of therapy in variant forms of CLL, namely mantle cell lymphoma and prolymphocytic leukemia, was uncommon in typical CLL. No unusual toxicity was noted at higher doses. Further exploration of the dosing schedule of rituximab in CLL and development of combination therapies is necessary. This agent shows promise for interaction in combined chemoimmunotherapy strategies for front-line and relapsed patients with CLL.
利妥昔单抗（美罗华；基因泰克公司，加利福尼亚州南旧金山和IDEC制药公司，加利福尼亚州圣地亚哥）是一种嵌合单克隆抗体，可靶向大多数淋巴B细胞恶性肿瘤中的成熟B细胞。利妥昔单抗已获美国食品药品监督管理局批准用于复发性B细胞淋巴瘤的治疗。在最初的临床试验中，其对小淋巴细胞淋巴瘤（慢性淋巴细胞白血病（CLL）的对应物）的活性低于20%。为了提高利妥昔单抗在CLL中的活性水平，我们进行了一项I期剂量递增研究，以克服与淋巴瘤细胞相比CLL细胞上较低的CD20抗原密度以及利妥昔单抗在小淋巴细胞淋巴瘤中较短的半衰期。在第1天初始给予375 mg/m²利妥昔单抗剂量后，患者队列在第2、3和4周接受递增剂量治疗。评估的利妥昔单抗最大剂量为2250 mg/m²。有明确证据表明存在剂量反应关系。在CLL的变异形式即套细胞淋巴瘤和幼淋巴细胞白血病中，首次治疗剂量后出现的严重毒性（3级和4级）在典型CLL中并不常见。在更高剂量下未观察到异常毒性。有必要进一步探索利妥昔单抗在CLL中的给药方案并开发联合疗法。该药物在CLL一线和复发患者的联合化疗免疫治疗策略中显示出相互作用的前景。
