WR-2721 as cytotoxic and radioprotective agent in treatment of murine lymphoma with total body irradiation.

NCI monographs : a publication of the National Cancer Institute Pub Date : 1988-01-01

L R Coia, D Q Brown, J Hardiman

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Abstract

The effectiveness of fractionated total body irradiation (TBI) in treatment of non-Hodgkin's lymphoma is limited by bone marrow toxicity. Because WR-2721 effectively protects bone marrow, we tested its potential in treatment of I-347 lymphoma in BALB/c mice, using various single and fractionated TBI regimens. In most treatment schedules, WR-2721 did not cause net lymphoma protection; in fact, it was cytotoxic. Lymphoma regrowth delay times for the 21 treatment groups were quite effectively fitted by a mathematical model with three components: 1) a dose-dependent radiation effect; 2) a small radioprotective effect by WR-2721; and 3) significant cytotoxicity of WR-2721. Bone marrow radioprotection was reduced when TBI was fractionated, but there was no evidence of WR-2721 cytotoxicity to marrow. The therapeutic gain due to WR-2721 was 2.5 for the five-fraction regimen, compared to 2.3 for a single fraction. The cumulative WR-2721 toxicity to lymphoma combined with marrow protection suggests that WR-2721 could increase the clinical therapeutic ratio of TBI, particularly fractionated TBI, in treatment of lymphoma.

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WR-2721在全身照射治疗小鼠淋巴瘤中的细胞毒性和辐射防护作用。

分次全身照射(TBI)治疗非霍奇金淋巴瘤的有效性受到骨髓毒性的限制。由于WR-2721有效地保护骨髓，我们测试了其治疗BALB/c小鼠I-347淋巴瘤的潜力，使用各种单一和分次TBI方案。在大多数治疗方案中，WR-2721不产生净淋巴瘤保护作用;事实上，它是细胞毒性的。21个治疗组的淋巴瘤再生延迟时间通过包含三个组成部分的数学模型非常有效地拟合:1)剂量依赖性辐射效应;2) WR-2721的辐射防护作用小;3) WR-2721具有显著的细胞毒性。骨髓放射保护在TBI分离后降低，但没有证据表明WR-2721对骨髓有细胞毒性。WR-2721在五组分方案中的治疗增益为2.5，而单组分方案的治疗增益为2.3。WR-2721对淋巴瘤的累积毒性结合骨髓保护作用提示WR-2721可提高TBI尤其是分路TBI治疗淋巴瘤的临床治疗率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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NCI monographs : a publication of the National Cancer Institute

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