Cornwell G G, Pajak T F, McIntyre O R, Kochwa S, Dosik H
Cancer Treat Rep. 1982 Mar;66(3):475-81.
The influence of renal insufficiency on melphalan-induced myelosuppression was examined during the initial 10 weeks of treatment in 295 patients with multiple myeloma. Patients were randomized to receive either oral melphalan (0.15 mg/kg/day for 7 days, followed by 0.05 mg/kg/day after recovery from the wbc count nadir) or iv melphalan (16 mg/m2 every 2 weeks for four doses, followed by a single dose every 4 weeks). All patients received a 6-week tapering course of prednisone. Patients with renal insufficiency (BUN greater than or equal to 30 mg/100 ml) had a significantly higher frequency of severe leukopenia (less than or equal to 1000 cells/mm3) following iv melphalan than did patients with normal renal function (50% vs 15%, respectively; P = 0.007). The latter effect resulted in an increased frequency of drug-related deaths secondary to infection. The frequency of severe thrombocytopenia (less than or equal to 25,000 cells/mm3) was also greater in patients with renal failure following iv melphalan therapy. Reduction of iv melphalan dose to 50% in patients with elevated BUN reduced the frequency of these complications to levels that were not significantly different from those observed in patients with normal renal function. The frequency of severe myelosuppression was independent of renal function in patients receiving oral melphalan. Possible explanations for these findings are discussed.
在295例多发性骨髓瘤患者治疗的最初10周内，研究了肾功能不全对美法仑诱导的骨髓抑制的影响。患者被随机分为口服美法仑组（0.15mg/kg/天，共7天，白细胞计数最低点恢复后改为0.05mg/kg/天）或静脉注射美法仑组（每2周16mg/m²，共四剂，之后每4周一剂）。所有患者均接受为期6周的泼尼松递减疗程。肾功能不全（血尿素氮大于或等于30mg/100ml）的患者静脉注射美法仑后严重白细胞减少（小于或等于1000细胞/mm³）的发生率显著高于肾功能正常的患者（分别为50%和15%；P = 0.007）。后一种效应导致感染继发的药物相关死亡频率增加。静脉注射美法仑治疗后，肾功能衰竭患者严重血小板减少（小于或等于25,000细胞/mm³）的发生率也更高。血尿素氮升高的患者将静脉注射美法仑剂量减少50%，可将这些并发症的发生率降低至与肾功能正常患者观察到的水平无显著差异。接受口服美法仑的患者严重骨髓抑制的发生率与肾功能无关。文中讨论了这些发现的可能解释。
