Efficacy and safety of metyrosine in pheochromocytoma/paraganglioma: a multi-center trial in Japan

Endocrine journal

Mitsuhide Naruse¹  Akiyo Tanabe²  Masatoshi Nomura³  Atsuhiro Ichihara⁴  Mika Tsuiki⁵  Masanobu Yamada⁶  Takuyuki Katabami⁷  Tomoaki Tanaka⁸  Takahiro Okamoto⁹  Tadashi Matsuda^1,10  Fumitoshi Satoh^1,11  Kazuhiro Takekoshi^1,12  Tsuneo Imai^1,13  Tomohiro Harada^1,14  Nobuyuki Kawata^1,14 

[1] Clinical Research Institute for Endocrinology and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan;Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo 162-8655, Japan;Department of Endocrine and Metabolic Diseases, Kyushu University Hospital, Fukuoka 812-8582, Japan;Department of Endocrinology and Hypertension, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan;Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511, Japan;Department of Metabolism and Endocrinology, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Yokohama 241-0811, Japan;Department of Molecular Diagnosis, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan;Department of Surgery II, Tokyo Women’s Medical University, Tokyo 162-8666, Japan;Department of Urology and Andrology, Kansai Medical University Hospital, Hirakata 573-1191, Japan;Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai 980-8574, Japan;Faculty of Medicine, University of Tsukuba, Tsukuba 305-8577, Japan;National Hospital Organization, Higashinagoya National Hospital, Nagoya 465-8620, Japan;Ono Pharmaceutical Co., Ltd., Osaka 541-8564, Japan

关键词: Metyrosine;    Catecholamines;    Pheochromocytoma;    Paraganglioma;    Multi-center clinical trial;   

DOI  :  10.1507/endocrj.EJ17-0276

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

To assess the efficacy, safety, and pharmacokinetics of metyrosine (an inhibitor of catecholamine synthesis) in patients with pheochromocytoma/paraganglioma (PPGL), we conducted a prospective, multi-center, open-label study at 11 sites in Japan. We recruited PPGL patients aged ≥12 years requiring preoperative or chronic treatment, receiving α-blocker treatment, having baseline urinary metanephrine (uMN) or normetanephrine (uNMN) levels ≥3 times the upper limit of normal values, and having symptoms associated with excess catecholamine. Metyrosine treatment was started at 500 mg/day and modified according to dose-adjustment criteria up to 4,000 mg/day. The main outcome measure was the proportion of patients who achieved at least 50% reduction in uMN or uNMN levels from baseline. Sixteen patients (11 males/5 females) aged 12–86 years participated. After 12 weeks of treatment and at the last evaluation of efficacy, the primary endpoint was achieved in 31.3% of all patients, including 66.7% of those under preoperative treatment and 23.1% of those under chronic treatment. Sedation, anemia, and death were reported in 1 patient each as serious adverse drug reactions during the 24-week treatment. Metyrosine was shown to be tolerated and to relieve symptoms by reducing excess catecholamine in PPGL patients under both preoperative and chronic treatment.

【 授权许可】

Unknown