Higano Celestia S, Quick Donald P, Bushnell David, Sartor Oliver
Medicine and Urology, University of Washington Medical Center, Division of Medical Oncology, Seattle, WA 98109, USA.
Clin Genitourin Cancer. 2008 Mar;6(1):40-5. doi: 10.3816/CGC.2008.n.007.
The safety and tolerability of repetitive doses of the boneseeking radiopharmaceutical samarium-153 lexidronam (153Sm- EDTMP) were investigated in men with hormone-naive prostate cancer metastatic to bone.
Within 30 days of initiating androgen deprivation, the first of 4 planned doses of 153Sm- EDTMP given every 12 weeks was administered. Growth factors were not permitted. The first cohort of 6 patients received 153Sm-EDTMP at 2 mCi/kg per dose; 3 patients completed all 4 doses and 3 received 3 doses.
There were 7 episodes of grade 3 neutropenia and 1 each of grade 3 and 4 thrombocytopenia. Of 6 patients in the second cohort who received 153Sm-EDTMP 2.5 mCi/kg per dose, only 1 received all 4 doses. Four events of grade 3 neutropenia and 2 events of grade 3 thrombocytopenia were reported. The 12-week dose schedule resulted in persistent low-grade thrombocytopenia and/or leukopenia, which prevented administration of all 4 planned doses. As a result, the dose of 153Sm-EDTMP was decreased to 2 mCi/kg for a total of 3 doses administered every 16 weeks. Five of 6 patients in this cohort received all 3 doses of 153Sm-EDTMP. There were 7 episodes of reversible grade 3 neutropenia. For all 18 patients on the study, there were no drug-related serious adverse events or grade 4 nonhemmatologic toxicities.
In men with hormone-naive prostate cancer metastatic to bone, the feasible dose and schedule for repeated doses of 153Sm-EDTMP is 2 mCi/kg given every 16 weeks for 3 doses.
在激素初治的骨转移前列腺癌男性患者中，研究重复剂量的亲骨性放射性药物钐-153 来昔膦酸（153Sm-EDTMP）的安全性和耐受性。
在开始雄激素剥夺治疗的 30 天内，给予每 12 周 1 次、共 4 次计划剂量的 153Sm-EDTMP 中的第 1 剂。不允许使用生长因子。首批 6 例患者接受的 153Sm-EDTMP 剂量为每千克体重 2 毫居里；3 例患者完成了全部 4 剂，3 例接受了 3 剂。
发生 7 次 3 级中性粒细胞减少事件，3 级和 4 级血小板减少事件各 1 次。在第 2 组接受每千克体重 2.5 毫居里 153Sm-EDTMP 的 6 例患者中，仅 1 例完成了全部 4 剂。报告了 4 次 3 级中性粒细胞减少事件和 2 次 3 级血小板减少事件。12 周的给药方案导致持续性轻度血小板减少和/或白细胞减少，使得无法给予全部 4 次计划剂量。因此，153Sm-EDTMP 的剂量减至每千克体重 2 毫居里，每 16 周共给予 3 剂。该组 6 例患者中有 5 例接受了全部 3 剂 153Sm-EDTMP。发生 7 次可逆性 3 级中性粒细胞减少事件。对于研究中的所有 18 例患者，未出现与药物相关的严重不良事件或 4 级非血液学毒性。
在激素初治的骨转移前列腺癌男性患者中，重复剂量 153Sm-EDTMP 的可行剂量和方案是每 16 周给予 2 毫居里/千克，共 3 剂。
