High-dose calcitriol and carboplatin in metastatic androgen-independent prostate cancer
High-dose calcitriol and carboplatin in metastatic androgen-independent prostate cancer
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DOI：
10.1097/01.coc.0000136020.27904.9c
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发表时间：
2004-10-01
影响因子：
2.6
通讯作者：
Katovic, NM
中科院分区：
文献类型：
--
作者：
Beer, TM;Garzotto, M;Katovic, NM
在前列腺腺癌的临床前模型中，骨化三醇与卡铂具有协同作用。作者试图在转移性雄激素非依赖性前列腺癌患者中测试高剂量口服骨化三醇与卡铂的联合治疗。 17 名患者在第 1 天接受口服骨化三醇（0.5 杯/公斤），在第 2 天接受静脉注射卡铂（既往接受过放射治疗的患者的 AUC 7 或 AUC 6），每 4 周重复一次。 PSA 反应是主要终点，定义为 4 周后确认下降 50%。还检查了姑息反应（当前疼痛强度 [PPI] 量表上的疼痛减轻 2 点或正常化，且不增加镇痛药用量）。 17 名患者中的一名（6%，95% CI，0-28）获得了确认的 PSA 缓解。 4 名患者（24%，95% CI，7-49）PSA 降低了 24% 至 38%。在入组时 PPI 大于或等于 1 分的 15 名患者中，有 3 名（18%，95% CI，4-48）符合姑息缓解标准。与治疗相关的毒性是轻微的，通常与单药卡铂的预期相似。尽管临床前证据令人鼓舞，但与报告的单独卡铂活性相比，本研究中在卡铂中添加口服骨化三醇与缓解率的增加无关。
Calcitriol acts synergistically with carboplatin in preclinical models of adenocarcinoma of the prostate. The authors sought to test high-dose oral calcitriol in combination with carboplatin in patients with metastatic androgen-independent prostate cancer. Seventeen patients received oral calcitriol (0.5 mug/kg) on day 1 and intravenous carboplatin (AUC 7 or AUC 6 in patients with prior radiation) on day 2, repeated every 4 weeks. PSA response was the primary end point and was defined as a 50% reduction confirmed 4 weeks later. Palliative response (2-point reduction or normalization of pain on the present pain intensity [PPI] scale without increased analgesic consumption) was also examined. One of 17 patients (6%, 95% CI, 0-28) achieved a confirmed PSA response. Four patients (24%, 95% CI, 7-49) had PSA reductions ranging from 24 to 38%. Of the 15 patients with a PPI greater than or equal to 1 point on entry, 3 (18%, 95% CI, 4-48) met criteria for palliative response. Treatment-related toxicity was mild and generally similar to that expected with single-agent carboplatin. Despite encouraging preclinical evidence, the addition of oral calcitriol to carboplatin in this study was not associated with an increase in the response rate when compared with the reported activity of carboplatin alone.