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Denosumab can prevent chemo-induced secondary BMD loss in GI cancer patients

Pearl Toh
04 Dec 2018

Administration of the RANKL* inhibitor denosumab prior to chemotherapy initiation may prevent secondary reduction in bone mineral density (BMD) induced by chemotherapy, according to the ESPRESSO-02 study presented at ESMO Asia 2018.

The previous ESPRESSO-01 study has shown that the reduction in BMD after only 16 weeks of chemotherapy with short-term periodic glucocorticoid premedication for GI cancer was comparable to that seen with 12-month adjuvant therapy with aromatase inhibitor for early-stage breast cancer patients. [Oncologist 2017;22:592-600]

In the current multicentre prospective ESPRESSO-02 study, 42 patients (median age 68 years, 42.9 percent male) with GI cancer received a single subcutaneous injection of denosumab 60 mg within a week before the induction of chemotherapy with glucocorticoid premedication. Intravenous steroid premedication was given either weekly, biweekly, or triweekly, with steroid-free intervals of >4 weeks not allowed. All patients were also supplemented with calcium 610 mg daily and vitamin D 400 IU daily. [ESMO Asia 2018, abstract 440P]      

Sixteen weeks after chemotherapy initiation, BMD levels were significantly increased from baseline in 73.2 percent of the patients, at an average rate of +2.8 percent in the lumbar spine (p<0.0001).

In comparison, 74.3 percent of the participants who did not receive denosumab prior to chemotherapy induction in ESPRESSO-01 saw their lumbar spine BMD levels decreased by an average of 1.89 percent from baseline (p<0.0001).     

“The lower limit of 95 percent confidence interval of BMD variation rate in this study was +1.350 and the primary endpoint was met,” the researchers stated.

In addition, BMD in the total hip (mean, +1.36 percent; p=0.004) and femoral neck (mean, +1.95 percent; p=0.022) also increased significantly at 16 weeks compared with baseline in the ESPRESSO-02 study.    

Other markers of bone turnover such as serum bone alkaline phosphatase (sBAP) and serum cross-linked N-telopeptides of type I collagen (sNTX) levels were decreased by 29.44 percent (p<0.0001) and 37.95 percent (p=0.034), respectively.

Furthermore, subgroup analysis showed that the protective effect of denosumab against chemotherapy-induced BMD loss was consistent across subgroups, regardless of age, gender, primary tumour site, treatment duration, additive oral steroid use, and baseline T-score.

No incidence of bone fracture was reported among the participants.

“We found that denosumab administration could prevent the secondary reduction of BMD,” the researcher concluded. “Further studies are needed to evaluate on the effectiveness of long-term prognosis, quality of life, and cost.”

  

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Most Read Articles
19 Nov 2019
Tumour diameter, depth and histological type are correlated with overtreatment with surgery in patients with early gastric cancer (EGC), a recent study has found.
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Discontinuation of antitumour necrosis factor (anti-TNF) therapy for perianal Crohn’s disease is highly likely to lead to relapse, with some patients even requiring defunctioning surgery, according to a study conducted across Asia.
Audrey Abella, 19 Nov 2019
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Roshini Claire Anthony, 07 May 2019

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