Coia L R, Brown D Q, Hardiman J
Department of Radiation Therapy, Fox Chase Cancer Center, Philadelphia, PA 19111.
NCI Monogr. 1988(6):235-9.
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.
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能有效保护骨髓，我们使用各种单次和分次TBI方案，测试了其对BALB/c小鼠I-347淋巴瘤的治疗潜力。在大多数治疗方案中，WR-2721并未带来净淋巴瘤保护作用；事实上，它具有细胞毒性。21个治疗组的淋巴瘤再生长延迟时间能很好地用一个包含三个部分的数学模型拟合：1）剂量依赖性辐射效应；2）WR-2721的微小辐射防护效应；3）WR-2721的显著细胞毒性。当TBI采用分次照射时，骨髓辐射防护作用减弱，但没有证据表明WR-2721对骨髓具有细胞毒性。对于五分次方案，WR-2721带来的治疗增益为2.5，而单次照射时为2.3。WR-2721对淋巴瘤的累积毒性与骨髓保护作用相结合，表明WR-2721可提高TBI（尤其是分次TBI）治疗淋巴瘤的临床治疗比。
