The role of bisphosphonates in the treatment of painful metastatic bone disease: a review of phase III trials

Pain ◽  
1998 ◽  
Vol 78 (3) ◽  
pp. 157-169 ◽  
Author(s):  
F Fulfaro ◽  
A Casuccio ◽  
C Ticozzi ◽  
C Ripamonti
Keyword(s):  
Bone Disease ◽  
Metastatic Bone Disease ◽  
Phase Iii ◽  
Phase Iii Trials

Hypocalcemia in patients with metastatic bone disease receiving denosumab.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9628-9628 ◽  
Author(s):  
Jean-Jacques Body ◽  
Allan Lipton ◽  
David H. Henry ◽  
Alison Stopeck ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Bone Disease ◽  
Bone Destruction ◽  
Metastatic Bone Disease ◽  
Phase Iii ◽  
Antiresorptive Agents ◽  
Spontaneous Reports ◽  
Phase Iii Trials ◽  
Post Marketing ◽  
Marketing Data ◽  
Grade 3

9628 Background: Patients (pts) with metastatic bone disease (MBD) are at risk of skeletal-related events (SREs). Potent antiresorptives reduce the risk of SREs, by inhibiting cancer-induced bone destruction, which also reduces release of skeletal calcium (Ca) into the bloodstream. Hypocalcemia (hypoCa) may occur if Ca and vit D intake is inadequate while taking antiresorptive agents. A combined analysis of 3 phase III trials in pts with MBD showed denosumab (DMAb) was superior to zoledronic acid (ZA) in preventing SREs. The overall safety profiles were similar; hypoCa was more common with DMAb (9.6%) than ZA (5.0%). Characteristics of hypoCa events in DMAb pts in these clinical trials and from post marketing adverse event (AE) reports are presented. Methods: Pts with solid tumors or multiple myeloma and MBD were randomized (1:1) to DMAb 120 mg SC or ZA 4 mg IV (adjusted for renal function) every 4 weeks (Q4W). Pts were advised to take daily Ca (≥ 500 mg) and vit D (≥ 400 IU); intake was collected by pt report. Albumin-corrected serum Ca was measured Q4W by central lab. HypoCa events were collected as decreases in serum Ca per central lab and investigator-reported AEs. Post marketing data from spontaneous reports of hypoCa to the sponsor's global safety department (AGS) were reviewed. Results: In the 3 trials, 2841 pts received DMAb and 2836 pts received ZA. The median Ca levels for both treatment groups were similar over time. Among DMAb pts, hypoCa was most common within 6 months of starting treatment and was more common in pts who did not report use of Ca and vit D vs those who did (15.8% vs 8.7%). Grade 3 or 4 (< 7 mg/dL; < 1.75 mmol/L) decreases in serum Ca were reported in 3.1% of DMAb pts and 1.3% of ZA pts. No fatal cases of hypoCa were reported in the trials. From May to Nov 2012, 37 cases of severe symptomatic hypoCa (seizures, tetany, prolonged QTc, altered mental state) were reported to AGS; fatal outcomes were reported for 3 other pts with advanced cancers and various comorbidities. Conclusions: HypoCa is a known risk with antiresorptive therapy, including DMAb 120 mg. HypoCa occurred less often in pts who reported taking Ca and vit D. HypoCa should be corrected prior to starting DMAb and Ca monitored during treatment. Pts should take adequate Ca and vit D while receiving DMAb. Clinical trial information: NCT00321464, NCT00321620, and NCT00330759.

Denosumab and zoledronic acid treatment in patients with genitourinary cancers and bone metastases.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5079-5079 ◽  
Author(s):  
Luis Costa ◽  
Karim Fizazi ◽  
Fred Saad ◽  
Janet Elizabeth Brown ◽  
Roger Von Moos ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Disease ◽  
Proportional Hazards Model ◽  
Transitional Cell ◽  
Cox Proportional Hazards ◽  
Metastatic Bone Disease ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Pivotal Phase ◽  
Significant Difference

5079 Background: Phase III trial results showed that denosumab is superior to zoledronic acid (ZA) in preventing skeletal-related events (SREs) in patients with cancer and metastatic bone disease (Lipton et al; 2012, Eur J Cancer). Genitourinary (GU) cancers are some of the most commonly diagnosed cancers worldwide. We now compare the efficacy and safety of denosumab (DMAb) or ZA in a subgroup analysis of patients with GU cancers enrolled in the pivotal phase III trials. Methods: Patients were randomized 1:1 to receive DMAb (120 mg, SC) or ZA (4 mg, IV, adjusted for renal function) every 4 weeks. Daily calcium and vitamin D supplements were strongly recommended. Time to 1st on-study SRE, using a Cox proportional hazards model, time to 1st and subsequent on-study SRE, using the Anderson-Gill model, and safety were evaluated for the GU subgroup in an ad hoc analysis. Results: 2,128 patients (1,052 DMAb; 1,076 ZA) had GU cancers (prostate = 1,901, renal = 155, bladder = 63, and transitional cell = 9). DMAb significantly delayed the time to 1st on-study SRE by 4.0 months compared with ZA (20.7 months vs 16.7 months) in patients with GU cancers (Table). DMAb also significantly delayed the time to 1st and subsequent on-study SRE. Time to disease progression and overall survival were similar between treatment groups. Adverse events (AEs) and serious AEs were reported by similar percentages of patients in both groups (AEs: 96.9% denosumab, 96.8% ZA; serious AEs: 62.8% denosumab, 60.2% ZA). 14.6% of DMAb pts and 15.9% of ZA pts had a renal AE. Hypocalcemia was reported for 12.9% of DMAb patients and 6.2% of ZA patients. There was no significant difference in the incidence of positively adjudicated osteonecrosis of the jaw between the DMAb (2.2%) and ZA (1.6%) groups (p=0.34). Conclusions: Among patients with GU cancers and metastatic bone disease, DMAb was superior to ZA in preventing SREs. Clinical trial information: NCT00330759 and NCT00321620. [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document