Nome Ragnhild, Hernes Eivor, Bogsrud Trond Velde, Bjøro Trine, Fosså Sophie D
Department of Medical Biochemistry and.
Scand J Urol. 2015 Jun;49(3):211-7. doi: 10.3109/21681805.2014.982169. Epub 2014 Dec 17.
The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223).
Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo.
Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients.
These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.
本研究旨在评估接受六个周期镭 - 223（Ra - 223）治疗的伴有骨转移的转移性去势抵抗性前列腺癌（mCRPC）患者中前列腺特异性抗原（PSA）、总碱性磷酸酶和骨碱性磷酸酶（总ALP、骨ALP）与治疗相关的变化，以及传统骨扫描的变化。
在14例伴有骨转移的mCRPC患者和4例接受安慰剂治疗的患者中，在每月一次、共六个周期的Ra - 223治疗（50 kBq/kg体重）前后，评估PSA、总ALP和骨ALP的变化（增加或减少≥30%）以及骨扫描的变化。
14例患者中有11例治疗后PSA至少升高30%，3例保持稳定。总ALP和骨ALP分别在6例和9例患者中降低。在12例可评估患者中，10例治疗后骨扫描显示，预处理时摄取高的病灶摄取减少，11例患者伴有新的或扩大的骨病灶形成。正电子发射断层扫描/计算机断层扫描（FACBC PET/CT）扫描证实2例患者有新的或扩大的骨转移灶生长。
这些观察结果支持以下观点，即Ra - 223可杀死被高度增殖的成骨细胞包围的转移灶中的肿瘤细胞，这与报道的生存获益一致。然而，在未被成骨细胞活性增加所包围的小肿瘤灶中，放射效应似乎不足，从而允许肿瘤持续生长。在Ra - 223治疗期间，PSA长期降低是例外而非普遍规律，而碱性磷酸酶更频繁降低。为提高总体抗癌效果，Ra - 223可能是联合治疗的一个有价值的组成部分。
