Czuczman M S
Lymphoma Section, Division of Hematologic Oncology and Bone Marrow Transplantation, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Semin Oncol. 1999 Oct;26(5 Suppl 14):88-96.
Indolent (low-grade) B-cell lymphomas are responsive to single-agent and combination chemotherapy agents, but unfortunately possess an incurable, relapsing nature. Novel agents and innovative treatment approaches need to be evaluated in these patients, with the ultimate goals of maintaining good quality of life and prolonging overall survival. Novel combinations of chemotherapeutic agents, monoclonal antibodies (both unlabeled and radiolabeled), and anti-idiotypic vaccine therapies are currently being evaluated. This article reports on the first successful clinical trial combining a chimeric anti-CD20 monoclonal antibody (rituximab; Rituxan, IDEC Pharmaceuticals, San Diego, CA, and Genentech, Inc, San Francisco, CA) with standard-dose combination chemotherapy (ie, cyclophosphamide/doxorubicin/vincristine/prednisone [CHOP]) in the treatment of patients with indolent B-cell lymphoma. A 95% overall response (55%, complete remission; 40%, partial remission) rate using strict definitions for complete remission and extensive staging studies was achieved in a 40-patient intent-to-treat group. In addition, seven of seven patients with follicular histologies achieving complete remission also had clearing of BCL-2 (chromosome 14;18 translocation) positivity from blood and marrow by sensitive polymerase chain reaction assay, suggesting the eradication of subclinical minimal residual disease. Based on its single-agent efficacy, excellent toxicity profile, and ability to be successfully combined with combination chemotherapy (ie, CHOP), rituximab is currently undergoing extensive investigation in a large number of worldwide clinical trials to determine its optimal use in the treatment of CD20-positive neoplasms.
惰性(低级别)B细胞淋巴瘤对单药和联合化疗药物有反应,但不幸的是具有不可治愈、易复发的特性。需要在这些患者中评估新型药物和创新治疗方法,最终目标是维持良好的生活质量并延长总生存期。目前正在评估化疗药物、单克隆抗体(未标记和放射性标记)以及抗独特型疫苗疗法的新型联合方案。本文报道了首例将嵌合抗CD20单克隆抗体(利妥昔单抗;美罗华,IDEC制药公司,加利福尼亚州圣地亚哥,以及基因泰克公司,加利福尼亚州旧金山)与标准剂量联合化疗(即环磷酰胺/阿霉素/长春新碱/泼尼松[CHOP])联合用于治疗惰性B细胞淋巴瘤患者的成功临床试验。在一个40例患者的意向性治疗组中,采用严格的完全缓解定义和广泛的分期研究,总缓解率达到95%(55%为完全缓解;40%为部分缓解)。此外,7例滤泡性组织学类型达到完全缓解的患者中,有7例通过敏感的聚合酶链反应检测,血液和骨髓中的BCL-2(染色体14;18易位)阳性也消失,提示亚临床微小残留病被清除。基于其单药疗效、良好的毒性谱以及与联合化疗(即CHOP)成功联合的能力,利妥昔单抗目前正在全球范围内的大量临床试验中进行广泛研究,以确定其在治疗CD20阳性肿瘤中的最佳应用。