Takeuchi Yasuhiro, Takahashi Shunsuke, Miura Daishu, Katagiri Makoto, Nakashima Noriaki, Ohishi Hiroko, Shimazaki Ryutaro, Tominaga Yoshihiro
Toranomon Hospital Endocrine Center, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Okinaka Memorial Institute for Medical Research, Tokyo, Japan.
J Bone Miner Metab. 2017 Nov;35(6):616-622. doi: 10.1007/s00774-016-0797-0. Epub 2016 Nov 21.
Pharmacological treatment of hypercalcemia is essential for patients with parathyroid carcinoma and intractable primary hyperparathyroidism (PHPT). Use of the calcimimetic cinacalcet hydrochloride (cinacalcet) is an option to treat such patients. We investigated the efficacy and safety of cinacalcet in Japanese patients with parathyroid carcinoma and intractable PHPT. Five Japanese patients with parathyroid carcinoma and two with intractable PHPT were enrolled in an open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated until the albumin-corrected serum calcium concentration decreased to 10.0 mg/dL or less or until dose escalation was considered not necessary or feasible. Serum calcium concentration at the baseline was 12.1 ± 1.3 mg/dL (mean ± standard deviation; range 10.4-14.6 mg/dL) and decreased to 10.1 ± 1.6 mg/dL (range 8.6-13.3 mg/dL) at the end of the titration phase with cinacalcet at a dosage of up to 75 mg three times a day. At the end of the titration phase, at least a 1 mg/dL reduction in serum calcium concentration from the baseline was observed in five patients (three with carcinoma and two with PHPT), and it decreased to the normocalcemic range in five patients (three with carcinoma and two with PHPT). Common adverse events were nausea and vomiting. One patient discontinued participation in the study because of an adverse event, liver disorder. Cinacalcet effectively relieved hypercalcemia in 60% of the Japanese patients with parathyroid carcinoma and might be effective in those with intractable PHPT. The drug might be tolerable and safe at a dosage of at most 75 mg three times a day.
对于甲状旁腺癌和难治性原发性甲状旁腺功能亢进症（PHPT）患者，高钙血症的药物治疗至关重要。使用拟钙剂盐酸西那卡塞（西那卡塞）是治疗此类患者的一种选择。我们研究了西那卡塞在日本甲状旁腺癌和难治性PHPT患者中的疗效和安全性。五名日本甲状旁腺癌患者和两名难治性PHPT患者参加了一项开放标签、单臂研究，该研究包括滴定阶段和维持阶段。西那卡塞剂量进行滴定，直到白蛋白校正的血清钙浓度降至10.0mg/dL或更低，或者直到认为剂量增加没有必要或不可行。基线时血清钙浓度为12.1±1.3mg/dL（平均值±标准差；范围10.4 - 14.6mg/dL），在滴定阶段结束时，使用剂量高达每日三次75mg的西那卡塞，血清钙浓度降至10.1±1.6mg/dL（范围8.6 - 13.3mg/dL）。在滴定阶段结束时，五名患者（三名甲状旁腺癌患者和两名PHPT患者）的血清钙浓度较基线至少降低了1mg/dL，五名患者（三名甲状旁腺癌患者和两名PHPT患者）的血清钙浓度降至正常血钙范围。常见的不良事件是恶心和呕吐。一名患者因不良事件（肝脏疾病）而停止参与研究。西那卡塞有效缓解了60%的日本甲状旁腺癌患者的高钙血症，可能对难治性PHPT患者也有效。该药物在每日三次最多75mg的剂量下可能是可耐受且安全的。
