Background: We previously reported that short-term periodic premedication of glucocorticoids (GCs) used with chemotherapy for gastrointestinal cancer (GIC) caused the reduction of bone mineral densities (BMD) (ESPRESSO-01 study; Oncologist 2017). We conducted this study to evaluate the efficacy and safety of denosumab for prevention of chemotherapy-induced BMD decrease. Methods: The eligibility criteria were as the follows: 1) Histologically confirmed GIC, including esophageal, gastric, pancreatic, and biliary cancer; 2) a schedule of periodical intravenous steroid administration as premedication that was weekly, biweekly, or triweekly, and in which >4-week steroid-free intervals were not allowed; 3) high-risk patient with steroid-induced secondary osteoporosis; 4) no prior treatment for osteoporosis. The dose of denosumab is 60mg administered as a single subcutaneous injection within a week before the induction of chemotherapy. All participants should receive adequate calcium and vitamin D supplementation. The primary endpoint was to investigate the BMD change on lumbar spine between baseline and 16 weeks after induction of chemotherapy. Results: From April 2017 to Feb 2018, 49 cases were enrolled. Two patients did not meet the inclusion criteria. One patient died before treatment and one patient refused just after enrollment. One case was not measured for BMD at baseline and three patients were not measured for BMD at 16 weeks, due to patient refusal, discontinuation of treatment, death and so on (41 cases were the full analysis set). In 30 cases (73.2% of FAS), the levels of BMD at 16w were significantly increased compared with baseline and the average percent change of BMD of lumbar spine was 2.767% (n = 41, 95% CI: 1.308% to 4.225%, p < 0.0001). No one suffered any bone fracture in FAS population. Conclusions: We found that denosumab administration could prevent the reduction of BMD and bone fracture. Clinical trial identification: UMIN000023855. Legal entity responsible for the study: Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Funding: Has not received any funding. Disclosure: M. Nakamura: Honoraria: AstraZeneca, Bayer Yakuhin, Chugai, Daiichi Sankyo, Merck Serono, Nippon Boehringer Ingelheim, Taiho, Takeda. Y. Tsuji: Honoraria: Merck Serono, Eli Lilly Japan, Chugai, Taiho, Ono, Daiichi Sankyo, Yakult Honsha, Eisai, Medicon. Y. Komatsu: Honoraria: Bayer Yakuhin, Chugai, Taiho, Takeda, Eli Lilly Japan; Research expenses: Ono, MSD, Eli Lilly Japan, Taiho, Daiichi Sankyo, Chugai. All other authors have declared no conflicts of interest.
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