Oral Presentation 5th International Symposium on Phaeochromocytoma and Paraganglioma 2017

Evidence for Efficacy and Safety of Metirosine in Pheochromocytoma/paraganglioma: a Multi-center Trial in Japan (#39)

MITSUHIDE NARUSE 1 , FUMITOSHI SATOH 2 , AKIYO TANABE 3 , TAKAHIRO OKAMOTO 4 , ATSUHIRO ICHIHARA 5 , MIKA TSUIKI 6 , TAKUYUKI KATABAMI 7 , MASATOSHI NOMURA 8 , TOMOAKI TANAKA 9 , TADASHI MATSUDA 10 , TSUNEO IMAI 11 , MASANOBU YAMADA 12 , TOMOHIRO HARADA 13 , NOBUYUKI KAWATA 14 , KAZUHIRO TAKEKOSHI 15
  1. Clinical Research Institute for Endocrinology and Metabolic Diseases, National Hospital Organization Kyoto Medical Center, KYOTO, JAPAN
  2. Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, MIYAGI, JAPAN
  3. Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, TOKYO, JAPAN
  4. Department of Surgery II, Tokyo Women's Medical University, TOKYO, JAPAN
  5. Department of Endocrinology and Hypertension, Tokyo Women's Medical University, TOKYO, JAPAN
  6. Department of Endocrinology and Metabolism, National Hospital Organization Kyoto Medical Center, KYOTO, JAPAN
  7. Department of metabolism and Endocrinology, St. Marianna University School of Medicine, Yokohama City Seibu Hospital, KANAGAWA, JAPAN
  8. Department of Endocrine and Metabolic Diseases, Kyushu University Hospital, FUKUOKA, JAPAN
  9. Department of Molecular Diagnosis, Chiba University Graduate School of Medicine, CHIBA, JAPAN
  10. Department of Urology and Andrology, Kansai Medical University Hospital, OSAKA, JAPAN
  11. National Hospital Organization, Higashinagoya National Hospital, AICHI, JAPAN
  12. Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, GUNMA, JAPAN
  13. Ono Pharmaceutical Co., Ltd, OSAKA, JAPAN
  14. Ono Pharmaceutical Co., Ltd, OSAKA, JAPAN
  15. Faculty of Medicine, University of Tsukuba, IBARAKI, JAPAN

Metirosine is an inhibitor of catecholamine synthesis used to ameliorate catecholamine-induced symptoms of patients with pheochromocytoma/paraganglioma (PPGL), approved by the United States Food and Drug Administration in 1979. This clinical trial was conducted in accordance with the principles of the Declaration of Helsinki and the Guideline for Good Clinical Practice to receive regulatory approval of metirosine in Japan (JAPIC CTI-152999).

Objective:

The aim of this study was to investigate the efficacy and safety of metirosine in PPGL in a multicenter, open-label clinical trial in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice in Japan (MCAP-J Study).

Patients:

PPGL patients aged≥12 years requiring preoperative or chronic treatment, with baseline urinary metanephrine (uMN) or normetanephrine (uNMN) levels≥3 times the upper limit of normal values; being treated with α-blockers; and with symptoms associated with excess catecholamine.

Results:

Sixteen patients aged 12-86 years participated, 11 males. After 12-week treatment, the proportion of patients who achieved at least 50% reduction of uMN or uNMN from baseline as the primary endpoint was achieved in 31.3% of all patients, 23.1% under chronic treatment, and 66.7% under preoperative treatment at the last evaluation of efficacy. The changing rate for uMN and uNMN were -46.8±24.3% and -42.3±17.5%, respectively. During 24-week treatment, commonly reported adverse events (AEs) related to metirosine were sedation and somnolence in 15 patients (mild in 12, moderate in 2 and severe in 1). Serious AEs related to metirosine were sedation, anemia, and death in 1 patient each. Sedation and anemia were resolved after cessation of metirosine. The cause of death was considered by the investigator to be possibly due to the underlying unresectable pheochromocytoma.

Conclusions:

Metirosine was shown to be effective and tolerated in relieving symptoms by reducing excess catecholamine in PPGL patients under both preoperative and chronic treatment.