Presant C A, Klahr C
Cancer. 1977 Oct;40(4):1386-9. doi: 10.1002/1097-0142(197710)40:4<1386::aid-cncr2820400403>3.0.co;2-f.
In order to determine whether piperazinedione used in low doses in combination with cyclophosphamide plus dimethyl-triazeno-imidazole carboxamide (DTIC) produced variable or severe myelosuppression, a Phase I Study was performed in 10 patients who received 16 courses of the three-drug combination. Although mild myelosuppression was consistently observed at doses of 4 mg piperazinedione, 400 mg cyclophosphamide, plus 400 mg DTIC, variable, severe, and prolonged myelosuppression was seen in three of six patients who received a dose of each of the drugs only 25% higher. The only other abnormality observed was nausea and vomiting. This study indicates that low doses of piperazinedione can produce variable and severe myelosuppression when used in combination with other myelosuppressive agents, and that only small increments in dosage may produce marked increases in the degree of myelosuppression. Future combination chemotherapy regimens employing piperazinedione should undergo cautious Phase I toxicity testing to avoid severe depression of blood counts.
为了确定低剂量的哌嗪二酮与环磷酰胺加二甲基三氮烯咪唑甲酰胺（DTIC）联合使用是否会产生不同程度或严重的骨髓抑制，对10例接受三联药物联合治疗16个疗程的患者进行了一项I期研究。尽管在使用4毫克哌嗪二酮、400毫克环磷酰胺加400毫克DTIC的剂量时始终观察到轻度骨髓抑制，但在6例接受每种药物剂量仅高出25%的患者中，有3例出现了不同程度、严重且持续时间较长的骨髓抑制。观察到的唯一其他异常是恶心和呕吐。这项研究表明，低剂量的哌嗪二酮与其他骨髓抑制药物联合使用时可产生不同程度和严重的骨髓抑制，且仅剂量的小幅增加就可能导致骨髓抑制程度显著增加。未来采用哌嗪二酮的联合化疗方案应进行谨慎的I期毒性试验，以避免严重的血细胞计数降低。
