Warrell R P, Bockman R S, Coonley C J, Isaacs M, Staszewski H
J Clin Invest. 1984 May;73(5):1487-90. doi: 10.1172/JCI111353.
Approximately two-thirds of patients who receive the anticancer drug gallium nitrate develop mild hypocalcemia. To evaluate the mechanism of drug-induced hypocalcemia, we tested the effects of gallium nitrate upon in vitro release of 45Ca++ from explanted fetal rat bones. The drug significantly inhibited 45Ca++ release in response to stimulation with both parathyroid hormone and a lymphokine preparation with osteoclast activating factor activity. The inhibitory effects on bone resorption were both time- and dose-dependent. Later, in a pilot study, we treated 10 patients who had cancer-related hypercalcemia with gallium nitrate administered by continuous infusion. All patients responded by a reduction of total serum calcium to normal or subnormal concentrations (13.8 +/- 1.05 mg/dl, mean +/- SD pretreatment, to 8.03 +/- 1.03 mg/dl, mean posttreatment nadir). Our results indicate that gallium nitrate effectively treats cancer-related hypercalcemia and that it probably acts by inhibiting calcium release from bone.
接受抗癌药物硝酸镓治疗的患者中,约三分之二会出现轻度低钙血症。为评估药物诱导低钙血症的机制,我们测试了硝酸镓对外植的胎鼠骨骼中45Ca++体外释放的影响。该药物显著抑制了甲状旁腺激素和具有破骨细胞激活因子活性的淋巴因子制剂刺激引起的45Ca++释放。对骨吸收的抑制作用具有时间和剂量依赖性。后来,在一项初步研究中,我们对10例癌症相关高钙血症患者进行了持续输注硝酸镓治疗。所有患者的血清总钙均降至正常或低于正常浓度(治疗前平均±标准差为13.8±1.05mg/dl,治疗后最低点平均为8.03±1.03mg/dl)。我们的结果表明,硝酸镓能有效治疗癌症相关高钙血症,其作用可能是通过抑制骨钙释放实现的。