A multicenter prospective study on the efficacy and safety of denosumab in gastrointestinal cancer patients receiving short-term periodic steroid premedication for prevention of chemotherapy-induced nausea and vomiting (ESPRESSO-02/HGCSG1602)

Abstract

Objective: We previously reported that short-term periodic premedication of glucocorticoids (GCs) used with chemotherapy for gastrointestinal cancer (GIC) caused the reduction of BMDs and the increase of serum bone alkaline phosphatase (BAP) (ESPRESSO-01 study; Oncologist 2017;22:592). Surprisingly, it seems that theBMD decreasing levels due to only the 16-week GC usage in GIC chemotherapy were comparable to that of the 12-month adjuvant aromatase inhibitor therapy for early stage breast cancer patients or the 12-month androgen deprivation therapy for nonmetastatic prostate cancer patients. So we conducted this study to evaluate the efficacy and safety of denosumab for prevention of chemotherapy-induced BMD decreasing. Trial design: This is a multicenter single-arm prospective study to evaluate the efficacy and safety of denosumab in GIC patients receiving the short-term periodic steroid premedication. The key eligibility criteria are as follows: 1) Histologically confirmed adenocarcinoma in GIC, including esophageal, gastric, pancreatic, and biliary cancer.; 2) A schedules of periodical intravenous steroid administration as premedication that was weekly, biweekly, and 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 60 mg 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 is to investigate the BMD change and bone turnover markers (serum NTX and BAP levels) between baseline and 16 weeks after induction of chemotherapy. And the secondary endpoints are to compare and evaluate the difference of primary site, treatment regimen, dose intensity of steroids, newly bone fractures, and the FRAX output.