Non-Hodgkin's Lymphoma-Berlin-Frankfurt-Münster Study Center, Justus Liebig University Giessen, Giessen, Germany.
J Clin Oncol. 2010 Jul 1;28(19):3115-21. doi: 10.1200/JCO.2009.26.6791. Epub 2010 Jun 1.
The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL.
Patients younger than age 19 years with CD20(+) B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m(2) administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had > or = 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity.
From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007).
Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.
利妥昔单抗在儿科 B 细胞非霍奇金淋巴瘤（B-NHL）中的活性尚未确定。我们进行了一项 II 期窗研究，以检查新诊断的儿科 B-NHL 中利妥昔单抗的活性和耐受性。
年龄小于 19 岁、至少有一个可测量部位的 CD20(+) B-NHL 患者符合条件。治疗包括在第 1 天静脉注射 375mg/m(2)的利妥昔单抗；同时治疗包括 rasburicase，IT 三联药物（甲氨蝶呤、阿糖胞苷和泼尼松龙）用于 CNS 阳性患者，仅用于过敏反应的类固醇。反应标准是在利妥昔单抗前 24 小时和第 5 天之前一个至三个病变的两个最大垂直直径的乘积和/或骨髓（BM）或外周血（PB）中blasts 的百分比。反应者有≥25%的至少一个病变或 BM 或 PBblasts 的减少，并且其他部位无疾病进展。反应率（RR）设定为 45%的不利活动或 65%的有利活动。
从 2004 年 4 月至 2008 年 8 月，共纳入 136 例患者。利妥昔单抗相关的国家癌症研究所常见毒性标准 3/4 毒性为一般状况，15%；疲劳，13%；过敏反应，7%；感染，3%；谷草转氨酶/谷丙转氨酶，8%；无毛细血管渗漏；无毒性死亡。由于退出研究（n=16）、CNS 阴性患者的 IT 治疗（n=8）、皮质类固醇治疗（n=3）、反应评估技术不足（n=21）或无可评估病变（n=1），49 例患者无法评估反应。在 87 例可评估患者中，36 例为反应者（RR，41.4%；95%CI，31%至 52%）；其中，67 例伯基特淋巴瘤中有 27 例，15 例弥漫性大 B 细胞淋巴瘤中有 7 例。在 BM（12 例）中观察到的反应频率高于实体瘤病变（108 例中的 36 例；P=0.007）。
利妥昔单抗作为单一药物在儿科 B-NHL 中具有活性，尽管 RR 低于 II 期计划要求。
