Incidence and outcomes of osteonecrosis of the jaw from an integrated analysis of three pivotal randomized double-blind, double-dummy phase 3 trials comparing denosumab and zoledronic acid for treatment of bone metastases in advanced cancer patients or myeloma

Bone ◽  
2011 ◽  
Vol 48 (1) ◽  
pp. S18-S19 ◽  
Author(s):  
J.E. Brown* ◽  
C.H. Barrios ◽  
I.J. Diel ◽  
T. Facon ◽  
K. Fizazi ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Osteonecrosis Of The Jaw ◽  
Integrated Analysis ◽  
Advanced Cancer Patients ◽  
Phase 3 ◽  
Double Blind

Results of a prospective, randomized, double-blind, double-dummy, Phase 3 study comparing denosumab with zoledronic acid for the treatment of breast cancer patients with bone metastases

Bone ◽  
2010 ◽  
Vol 46 ◽  
pp. S36-S37 ◽  
Author(s):  
Jean-Jacques Body ◽  
Alison Stopeck ◽  
Yasuhiro Fujiwara ◽  
Allan Lipton ◽  
Guenther Steger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Phase 3 ◽  
Double Blind

Randomized, Double-Blind Study of Denosumab Versus Zoledronic Acid in the Treatment of Bone Metastases in Patients With Advanced Cancer (Excluding Breast and Prostate Cancer) or Multiple Myeloma

2011 ◽  
Vol 29 (9) ◽  
pp. 1125-1132 ◽  
Author(s):  
David H. Henry ◽  
Luis Costa ◽  
Francois Goldwasser ◽  
Vera Hirsh ◽  
Vania Hungria ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Adverse Events ◽  
Bone Metastases ◽  
Advanced Cancer ◽  
Subcutaneous Administration ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Osteonecrosis Of The Jaw ◽  
Double Blind Study ◽  
Double Blind

Purpose This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. Patients and Methods Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. Conclusion Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.

scholarly journals Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies

2017 ◽  
Vol 11 (3) ◽  
pp. 119-133 ◽  
Author(s):  
Marie T Fallon ◽  
Eberhard Albert Lux ◽  
Robert McQuade ◽  
Sandro Rossetti ◽  
Raymond Sanchez ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cancer Patients ◽  
Treatment Period ◽  
Advanced Cancer ◽  
Treatment Effect ◽  
Opioid Therapy ◽  
Advanced Cancer Patients ◽  
Phase 3 ◽  
Double Blind ◽  
The World

Background: Opioids are critical for managing cancer pain, but may provide inadequate relief and/or unacceptable side effects in some cases. Objective: To assess the analgesic efficacy of adjunctive Sativex (Δ9-tetrahydrocannabinol (27 mg/mL): cannabidiol (25 mg/mL)) in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. Methods: This report describes two phase 3, double-blind, randomized, placebo-controlled trials. Eligible patients had advanced cancer and average pain numerical rating scale (NRS) scores ≥4 and ≤8 at baseline, despite optimized opioid therapy. In Study-1, patients were randomized to Sativex or placebo, and then self-titrated study medications over a 2-week period per effect and tolerability, followed by a 3-week treatment period. In Study-2, all patients self-titrated Sativex over a 2-week period. Patients with a ≥15% improvement from baseline in pain score were then randomized 1:1 to Sativex or placebo, followed by 5-week treatment period (randomized withdrawal design). Results: The primary efficacy endpoint (percent improvement (Study-1) and mean change (Study-2) in average daily pain NRS scores) was not met in either study. Post hoc analyses of the primary endpoints identified statistically favourable treatment effect for Sativex in US patients <65 years (median treatment difference: 8.8; 95% confidence interval (CI): 0.00–17.95; p = 0.040) that was not observed in patients <65 years from the rest of the world (median treatment difference: 0.2; 95% CI: −5.00 to 7.74; p = 0.794). Treatment effect in favour of Sativex was observed on quality-of-life questionnaires, despite the fact that similar effects were not observed on NRS score. The safety profile of Sativex was consistent with earlier studies, and no evidence of abuse or misuse was identified. Conclusions: Sativex did not demonstrate superiority to placebo in reducing self-reported pain NRS scores in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy, although further exploration of differences between United States and patients from the rest of the world is warranted.

Denosumab versus zoledronic acid (ZA) for the treatment of bone metastases: An integrated analysis of results from 2 randomized, double-blind, phase 3 trials

Bone ◽  
2011 ◽  
Vol 48 (1) ◽  
pp. S21
Author(s):  
A. Lipton* ◽  
A. Stopeck ◽  
R. von Moos ◽  
D. Henry ◽  
G. Richardson ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Bone Metastases ◽  
Integrated Analysis ◽  
Phase 3 ◽  
Double Blind ◽  
Analysis Of Results

Pain Control with Morphine for Vertebral Metastases and Sciatica in Advanced Cancer Patients

1994 ◽  
Vol 10 (1) ◽  
pp. 10-13 ◽  
Author(s):  
Hideo Yoshioka ◽  
Satoru Tsuneto ◽  
Tetsuo Kashiwagi
Keyword(s):  
Bone Metastases ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Bone Pain ◽  
Malignant Tumors ◽  
Spinal Metastases ◽  
Pelvic Bone ◽  
Advanced Cancer Patients ◽  
Direct Invasion ◽  
High Doses

Morphine was administered to 56 advanced cancer patients; of that number spinal metastases had induced bone pain in 28 and malignant tumors had induced sciatica in 28. The sciatica was caused in 16 patients by direct invasion of the sacral plexus, in four by lumbar bone metastases, and in eight by pelvic bone metastases. Spinal bone pain was controlled adequately with morphine. However, sciatica required larger dosages of morphine than did bone pain. Among the group with sciatica, rectal cancer patients needed larger dosages of morphine than the other cancer patients. Even with high doses of morphine, it was occasionally difficult to control neuropathic pain of the sciatic nerve caused by intrapelvic cancer.

Multicenter case registry study on medication-related osteonecrosis of the jaw in advanced cancer patients.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e21663-e21663
Author(s):  
Morten Schiodt ◽  
Saroj Vadhan-Raj ◽  
Mark Steven Chambers ◽  
Ourania Nicolatou-Galitis ◽  
Constantinus Politis ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Osteonecrosis Of The Jaw ◽  
Registry Study ◽  
Advanced Cancer Patients

Zoledronic acid for hormone-naive prostate cancer with bone metastasis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16092-e16092
Author(s):  
Masahiro Nozawa ◽  
Isao Hara ◽  
Kazuhiro Nagao ◽  
Hideyasu Matsuyama ◽  
Hirotsugu Uemura
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Osteonecrosis Of The Jaw ◽  
Bone Diseases ◽  
Free Survival ◽  
Early Introduction ◽  
Treatment Naïve

e16092 Background: The potency of zoledronic acid for hormone-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefit of administering zoledronic acid concomitant with androgen-deprivation therapy in treatment-naïve prostate cancer patients with bone metastases, in which the primary endpoint was skeleton-related event (SRE)-free survival at 24 months after treatment. Methods: Treatment-naïve male patients with histologically confirmed adenocarcinoma of the prostate and radiologic evidence of bone metastasis were eligible. Treatment consisted of bicalutamide 80 mg administered orally on Day 1 and every day, goserelin acetate 10.8 mg administered subcutaneously on Day 8 and every 12 weeks, and zoledronic acid 4 mg administered intravenously on Day 8 and every four weeks. Results: Between July 2008 and April 2010, a total of 53 patients were enrolled and 52 evaluable. Median age was 72 years (range, 55 - 86). Median primary PSA was 249.4 ng/ml (range, 2.19 –19201). Median follow-up period was 33.3 months. The SRE-free survival rate at 24 months after treatment was 82.7 %. Median time to PSA progression was 25.9 months (95% confidential interval, 17.97-24.43). The score of the extent of bone diseases was stable or decreased in 73 % of the patients at 24 months after treatment. The grade-3 osteonecrosis of the jaw was reported in three patients (5.8 %). Conclusions: Our results suggest the potency of the early introduction of zoledronic acid for prostate cancer patients with bone metastases. Future studies are certainly required to ascertain the most appropriate timing of the commencement of zoledronic acid for patients with bone-metastatic prostate cancer. Clinical trial information: UMIN000007548.

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