Open AccessEfficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer
Author(s) -
Kôichi Sakaguchi,
Hisako Ono,
Katsuhiko Nakatsukasa,
Takashi Ishikawa,
Yoshie Hasegawa,
Masato Takahashi,
Naoki Niikura,
Kei Koizumi,
Teruhisa Sakurai,
Hideo Shigematsu,
Shunji Takahashi,
Shinichiro Taira,
Masato Suzuki,
Kazutaka Narui,
Daishu Miura,
Kimito Yamada,
Mana Yoshimura,
Hisashi Shioya,
Eiichi Konishi,
Yokota Isao,
Kojiro Imai,
Kei Fujikawa,
Tetsuya Taguchi
Publication year - 2019
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000016770
Subject(s) - medicine , denosumab , anastrozole , letrozole , breast cancer , clinical endpoint , aromatase inhibitor , bone mineral , oncology , osteoporosis , clinical trial , aromatase , cancer , surgery
Background: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. Patients and methods: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I–IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1–L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were (1) rate of change in the lumbar spine (L1–L4) BMD after 2, 3, 4, and 5 years; (2) rate of change in the femoral neck BMD; (3) rate of change in radius BMD (determined using an ultrasonic bone densitometer); (4) changes in calcium and bone metabolism markers (TRAP 5b, bone alkaline phosphatase, and pentosidine); (5) development of pathological fracture within 3 years; (6) disease-free survival; (7) overall survival (OS); (8) adverse events; and (9) quality of life.Ethics and dissemination: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. Trial registration: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.