Nilsson Sten, Larsen Roy H, Fosså Sophie D, Balteskard Lise, Borch Kari W, Westlin Jan-Erik, Salberg Gro, Bruland Oyvind S
Radiumhemmet, The Karolinska Hospital and Institute, Stockholm, Sweden.
Clin Cancer Res. 2005 Jun 15;11(12):4451-9. doi: 10.1158/1078-0432.CCR-04-2244.
The main goals were to study the safety and tolerability of the alpha-emitter radium-223 (223Ra) in breast and prostate cancer patients with skeletal metastases. In addition, pain palliation was evaluated.
Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial received a single i.v. injection of 223Ra. Five patients were included at each of the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative response was evaluated according to the pain scale of the European Organization for Research and Treatment of Cancer QLQ C30 questionnaire at baseline and at 1, 4, and 8 weeks after injection.
Weekly blood sampling during follow-up revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the injection. Importantly, for thrombocytes only grade 1 toxicity was reported. Grade 3 neutropenia and leucopenia occurred in two and three patients, respectively. Mild, transient diarrhea was observed in 10 of the 25 patients. Nausea and vomiting was more frequently observed in the highest dosage group. Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and 52.1% in males. Pain relief was reported by 52%, 60%, and 56% of the patients after 7 days, 4, and 8 weeks, respectively. 223Ra cleared rapidly from blood and was below 1% of initial level at 24 hours. Gamma camera images indicated, in accordance with pretreatment (99m)Tc-MDP scans, accumulation of 223Ra in skeletal lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
223Ra was well tolerated at therapeutically relevant dosages. Phase II studies have therefore been initiated.
主要目标是研究α发射体镭-223（223Ra）在伴有骨转移的乳腺癌和前列腺癌患者中的安全性和耐受性。此外，还对疼痛缓解情况进行了评估。
15名前列腺癌患者和10名乳腺癌患者参加了一项I期试验，接受了单次静脉注射223Ra。每个剂量组纳入5名患者，剂量分别为46、93、163、213或250 kBq/kg，并随访8周。根据欧洲癌症研究与治疗组织QLQ C30问卷的疼痛量表，在基线以及注射后1、4和8周评估姑息反应。
随访期间每周进行血液采样显示，注射后2至4周出现轻度且可逆的骨髓抑制，最低点出现。重要的是，仅报告了血小板1级毒性。分别有2名和3名患者出现3级中性粒细胞减少和白细胞减少。25名患者中有10名出现轻度、短暂性腹泻。最高剂量组更频繁地观察到恶心和呕吐。血清碱性磷酸酶下降，女性平均最低点下降29.5%，男性为52.1%。分别有52%、60%和56%的患者在7天、4周和8周后报告疼痛缓解。223Ra从血液中迅速清除，24小时时低于初始水平的1%。γ相机图像显示，与注射前（99m）Tc-MDP扫描一致，223Ra在骨病变中蓄积。消除主要通过肠道。中位生存期超过20个月。
223Ra在治疗相关剂量下耐受性良好。因此已启动II期研究。
