Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma
Maximum-tolerated dose, toxicity, and efficacy of 131I-Lym-1 antibody for fractionated radioimmunotherapy of non-Hodgkin's lymphoma
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DOI：
10.1200/jco.1998.16.10.3246
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发表时间：
1998-10-01
影响因子：
45.3
通讯作者：
Lewis, JP
中科院分区：
文献类型：
--
作者：
DeNardo, GL;DeNardo, SJ;Lewis, JP
目的：Lym-1是一种优先靶向恶性淋巴细胞的单克隆抗体，当用碘131（I-131）标记时，可诱导非霍奇金淋巴瘤（NHL）患者缓解。基于对总剂量进行分次给药的策略，本研究旨在确定最多4次I-131-Lym-1给药（间隔4周）中前两次给药的最大耐受剂量（MTD）和疗效。材料与方法：20例晚期NHL患者，共21个疗程。21个条目中有13个（62%）具有弥漫性大细胞组织学。所有患者均对标准治疗具有耐药性，平均接受了四种化疗方案。在给予I-131后给予I-131-IB-I，并且在患者队列中将I-131从40 mCi递增至100 mCi结果：骨髓和血中I-131的平均剂量为0.34（范围：0.16至0.63）rad/mCi（0.09 mGy/MBq;范围：0.04至0.17 mGy/MBq）。剂量限制性毒性为3 - 4级血小板减少症，间隔4周给予I-131-Lym-1的前两个剂量的MTD均为100 mCi/m2（3.7 GBq/m2）。除1例3级低血压外，非血液学毒性均不超过2级。接受至少两剂I-131-Lym-1治疗的14名患者中有10名（71%）和21名患者中有11名（52%）有应答。7份答复是完整的，平均持续时间为14个月。100 mCi/m2（3.7 MBq/m2）队列中的所有3例患者均获得完全缓解（CR）。结论：I-131-Lym-1可使化疗耐药的NHL患者获得持久缓解，且毒副反应可接受。I-131-Lym-1前两次给药的非清髓性MTD均为100 mCi/m2（总计200 mCi/m2）（3.7 GBq/m2;总计7.4 GBq/m2）。(C)1998年，美国临床肿瘤学会。
Purpose: Lym-1, a monoclonal antibody that preferentially targets malignant lymphocytes, has induced remissions in patients with non-Hodgkin's lymphoma (NHL) when labeled with iodine 131 (I-131). Based on the strategy of fractionating the total dose, this study was designed to define the maximum-tolerated dose (MTD) and efficacy of the first two, of a maximum of four, doses of I-131-Lym-1 given 4 weeks apart. Additionally, toxicity and radiation dosimetry were assessed.Materials and Methods: Twenty patients with advanced NHL entered the study a total of 21 rimes. Thirteen (62%) of the 21 entries had diffuse large-cell histologies. All patients had disease resistant to standard therapy and had received a mean of four chemotherapy regimens. I-131-Lym-l was given after Lym-l and I-131 was escalated in cohorts of patients from 40 to 100 mCi (1.5 to 3.7 GBq)/m(2) body surface area.Results: Mean radiation dose to the bone marrow from body and blood I-131 was 0.34 (range, 0.16 to 0.63) rad/mCi (0.09 mGy/MBq; range, 0.04 to 0.17 mGy/MBq). Dose-limiting toxicity was grade 3 to 4 thrombo cytopenia with an MTD af 100 mCi/m(2) (3.7 GBq/m(2)) for each of the first two doses of I-131-Lym-1 given 4 weeks apart. Nonhematologic toxicities did not exceed grade 2 except for one instance of grade 3 hypotension. Ten (71%) of 14 entries who received at least two doses of I-131-Lym-1 therapy and 11 (52%) of 21 total entries responded. Seven of the responses were complete, with a mean duration of 14 months. All three entries in the 100 mCi/m2 (3.7 MBq/m(2)) cohort held complete remissions (CRs). All responders had at least a partial remission (PR) after the first therapy dose of I-131-Lym-1.Conclusion: I-131-Lym-1 induced durable remissions in patients with NHL resistant to chemotherapy and was associated with acceptable toxicity. The nonmyeloablative MTD for each of the first two doses of I-131-Lym-1 was 100 mCi/m(2) (total, 200 mCi/m(2)) (3.7 GBq/m(2); total, 7.4 GBq/m(2)). (C) 1998 by American Society of Clinical Oncology.