de Klerk J M, Zonnenberg B A, van het Schip A D, van Dijk A, Han S H, Quirijnen J M, Blijham G H, van Rijk P P
Department of Nuclear Medicine, University Hospital Utrecht, The Netherlands.
Eur J Nucl Med. 1994 Oct;21(10):1114-20. doi: 10.1007/BF00181067.
Rhenium-186 hydroxyethylidene diphosphonate (186Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using 186Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the 186Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq 186Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10(9)/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% +/- 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of 186Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of 186Re-HEDP has been initiated.
铼-186 羟乙二膦酸盐（186Re-HEDP）已被用于转移性骨痛的姑息治疗。使用186Re-HEDP进行了一项1期剂量递增研究。24例激素抵抗性前列腺癌患者进入该研究。每位患者至少有四处骨转移且血液学功能良好。至少连续三名患者为一组，起始剂量为1295 MBq，以555 MBq的增量递增至3515 MBq进行治疗。血小板减少症被证明是剂量限制性毒性，而白细胞减少症起的作用较小。一名患者（给药后10天）早期死亡，与186Re-HEDP治疗无明确关系。两例出现短暂性神经功能障碍。两名接受3515 MBq 186Re-HEDP治疗的患者出现3级毒性（血小板25 - 50×10⁹/L），定义为不可接受的毒性。治疗后所有患者碱性磷酸酶水平均出现短暂下降（平均值：26%±10% IU/L；范围：11% - 44%）。八名患者前列腺特异性抗原值下降，其中三名患者在此之前有短暂升高。从这项研究我们得出结论，186Re-HEDP的最大耐受剂量为2960 MBq。一项关于186Re-HEDP疗效的安慰剂对照比较研究已启动。
