Lin Thomas S, Lucas Margaret S, Byrd John C
The Ohio State University, The Arthur James Comprehensive Cancer Center, Columbus, OH, USA.
Semin Oncol. 2003 Aug;30(4):483-92. doi: 10.1016/s0093-7754(03)00239-2.
The monoclonal anti-CD20 antibody rituximab exerts its antitumor activity through a variety of mechanisms, including acting against the cellular defects in apoptosis that give rise to B-chronic lymphocytic leukemia (B-CLL). Phase II clinical studies demonstrated that rituximab, given weekly as a single agent, exhibits significantly less activity in B-CLL than in indolent B-cell lymphomas. Dose escalation, achieved by a thrice-weekly dosing schedule, is necessary for rituximab to effect significant clinical activity as a single agent. A multicenter, prospective, randomized trial demonstrated that concurrent administration with fludarabine improves the complete response (CR) rate. Ongoing clinical studies are examining the use of rituximab in other combination regimens, including FCR (fludarabine, cyclophosphamide, and rituximab), which has shown great promise in a single-center phase II trial. B-CLL patients may experience more infusion toxicity, including tumor lysis syndrome, to rituximab than patients with lymphoma. However, such infusion toxicity is minimized with appropriate premedication and a stepped up dosing schedule, allowing safe and effective use of rituximab in this disease.
单克隆抗CD20抗体利妥昔单抗通过多种机制发挥其抗肿瘤活性，包括针对导致B细胞慢性淋巴细胞白血病（B-CLL）的细胞凋亡缺陷。II期临床研究表明，利妥昔单抗作为单一药物每周给药时，在B-CLL中的活性明显低于惰性B细胞淋巴瘤。通过每周三次给药方案实现剂量递增，对于利妥昔单抗作为单一药物发挥显著临床活性是必要的。一项多中心、前瞻性、随机试验表明，与氟达拉滨联合使用可提高完全缓解（CR）率。正在进行的临床研究正在研究利妥昔单抗在其他联合方案中的应用，包括FCR（氟达拉滨、环磷酰胺和利妥昔单抗），该方案在单中心II期试验中显示出巨大前景。与淋巴瘤患者相比，B-CLL患者使用利妥昔单抗时可能会出现更多的输注毒性，包括肿瘤溶解综合征。然而，通过适当的预处理和逐步增加的给药方案，这种输注毒性可降至最低，从而使利妥昔单抗能够安全有效地用于这种疾病。
