scholarly journals Acute Phase Reactions After Intravenous Infusion of Zoledronic Acid in Japanese Patients with Osteoporosis: Sub-analyses of the Phase III ZONE Study

2021 ◽  
Author(s):  
Masataka Shiraki ◽  
Tatsuhiko Kuroda ◽  
Yasuhiro Takeuchi ◽  
Toshitsugu Sugimoto ◽  
Satoshi Tanaka ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Acute Phase ◽  
Intravenous Infusion ◽  
Japanese Patients ◽  
Phase Iii ◽  
Total Hip ◽  
Hip Bmd ◽  
Baseline Factors ◽  
Post Hoc ◽  
Acute Phase Reactions

AbstractIn a clinical trial involving Japanese patients with osteoporosis, post hoc analyses were performed to evaluate the incidence of acute phase reactions (APRs) after infusion of zoledronic acid (ZOL). The results highlighted differences in baseline factors between patients with vs without APRs. Changes in efficacy indicators such as bone turnover markers (BTMs) also showed significant differences. We, therefore, investigated the factors involved in the development of APRs in Japanese patients treated with a once-yearly intravenous infusion of ZOL 5 mg for 2 years by assessing the relation between APRs and efficacy. APRs reported in patients with primary osteoporosis from the ZONE study were analyzed post hoc. Baseline factors were compared in patients with vs without APRs, and changes in BTMs and bone mineral density (BMD) were also investigated. In the ZOL group, 51.2% (169/330) of patients developed APRs after the first infusion and 12.3% (33/268) after the second infusion. Comparison of baseline factors showed that patients without APRs in the ZOL group had a significantly higher neutrophil/lymphocyte ratio, lower serum levels of procollagen type I N-terminal propeptide, older age, and higher likelihood of prior bisphosphonate use vs patients with APRs. Patients with APRs showed significantly higher increases in total hip BMD at 6 and 12 months and larger reductions in BTMs vs patients without APRs. Patient profiles differed significantly between patients with vs without APRs, with APRs after the first infusion of ZOL being related to increases in total hip BMD and suppression of BTMs.This study is registered with ClinicalTrials.gov (identifier: NCT01522521; January 31, 2012).

scholarly journals Nomogram for Predicting Survival in Patients Treated with Liposomal Irinotecan Plus Fluorouracil and Leucovorin in Metastatic Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1068 ◽  
Author(s):  
Chen ◽  
Macarulla ◽  
Blanc ◽  
Mirakhur ◽  
Jong ◽  
...  
Keyword(s):  
Carbohydrate Antigen ◽  
Phase Iii ◽  
Disease Stage ◽  
Ductal Adenocarcinoma ◽  
Karnofsky Performance Score ◽  
Neutrophil Lymphocyte Ratio ◽  
Baseline Factors ◽  
Liposomal Irinotecan ◽  
Aid Decision ◽  
Post Hoc

NAPOLI-1 (NCT01494506) was a phase III study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. This post hoc analysis of NAPOLI-1 aimed to develop a predictive nomogram for overall survival (OS) at 6 and 12 months. Analyses were derived from all patients in NAPOLI-1 randomized to receive nal-IRI+5-FU/LV, nal-IRI monotherapy, or 5-FU/LV combination therapy. OS was associated with baseline factors using univariate and multivariable Cox analyses. A predictive nomogram was derived and validated using a concordance index and calibration plots. The univariate analyses identified 21 independent factors that contributed to OS, with eight factors significantly associated with OS. The Karnofsky Performance Score contributed the largest number of points (100), followed by presence of liver metastasis (98) and randomization to nal-IRI+5-FU/LV (96). The other baseline factors showing effects were albumin (g/dL), neutrophil/lymphocyte ratio, carbohydrate antigen 19-9 (U/mL), disease stage at diagnosis, and body mass index (kg/m2). The nomogram was used to predict the 6- and 12-month survival probability. The mean absolute errors between the observed and predicted probabilities for OS at 3, 6, and 9 months were 0.07, 0.08, and 0.07, respectively. This nomogram, based on NAPOLI-1, provides additional insight to aid decision-making for patients with mPDAC after previous gemcitabine-based therapy.

ACUTE PHASE REACTIONS AFTER ZOLEDRONIC ACID INFUSION: PROTECTIVE ROLE OF 25-HYDROXYVITAMIN D AND PREVIOUS ORAL BISPHOSPHONATE THERAPY

2018 ◽  
Vol 24 (5) ◽  
pp. 405-410 ◽  
Author(s):  
Chiara Crotti ◽  
Nelson B. Watts ◽  
Maria De Santis ◽  
Angela Ceribelli ◽  
Gianluigi Fabbriciani ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Acute Phase ◽  
Protective Role ◽  
Bisphosphonate Therapy ◽  
Acid Infusion ◽  
Hydroxyvitamin D ◽  
Oral Bisphosphonate ◽  
25 Hydroxyvitamin D ◽  
Acute Phase Reactions

Efficacy of non-steroidal anti-inflammatory drugs on zoledronic acid-induced acute-phase reactions: randomized, open-label, Japanese OZ study

2019 ◽  
Vol 38 (2) ◽  
pp. 230-239 ◽  
Author(s):  
Nobukazu Okimoto ◽  
Akinori Sakai ◽  
Toru Yoshioka ◽  
Tomohiro Kobayashi ◽  
Kei Asano ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Acute Phase ◽  
Open Label ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Acute Phase Reactions

scholarly journals SUN-333 Burosumab Improves Bone Density in Patients with X-Linked Hypophosphatemia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Keerti Murari ◽  
Karl Leonard Insogna
Keyword(s):  
Trabecular Bone ◽  
Human Monoclonal Antibody ◽  
Phase Iii ◽  
Mineral Density ◽  
Paired Data ◽  
Total Hip ◽  
Skeletal Mass ◽  
Significant Difference ◽  
Hip Bmd ◽  
The Impact

Abstract Background: X-linked hypophosphatemia (XLH) causes rickets in children and osteomalacia in adults due to lifelong renal phosphate wasting that is mediated by high circulating levels of FGF-23. Burosumab, is a recently approved fully human monoclonal antibody that blocks FGF23, thereby correcting the renal phosphate leak, improving mineral metabolism and reducing osteomalacia by 50-75% in adults [1]. Whether this results in measurable changes in skeletal mass and microarchitecture is unclear. Objective: We examined the impact of burosumab on regional bone mineral density (BMD) and trabecular bone scores (TBS) in study subjects involved in two phase III clinical trials of burosumab. Methods: In these trails subjects received burosumab 1 mg/kg every 4 weeks. Some patients received placebo for the first 6 months of one trial so we considered their month 6 data as their baseline. Most of the patients had been treated at some point in the past with calcitriol and phosphorus. DXA and TBS were obtained at baseline and then after 6, 12 and 18-24 months of drug treatment. Paired t-tests and ANOVA were performed to assess changes in L-spine BMD, Total Hip BMD and TBS. Results: 25 subjects with XLH (mean age 38.9 years, 56% female) were enrolled in these studies. Paired data were available in 23 subjects at 6 months, 15 subjects at 12 months and 18 subjects at 18-24 months. Compared to baseline, there were significant increases in L-spine BMD at all time points by paired analysis: 6 months (+6.0%, p=<0.0001), 12 months (+6.95%, p=<0.0001), 18-24 months (+6.13%, p=0.0005). Although there was no significant difference in total hip BMD at 6 months when compared to baseline, there were significant increases at 12 months (+6.72%, p=0.0005) and a further increase at 18-24 months (+10.02%, p=0.0029). When all available subjects were analyzed by one-way ANOVA, there was a significant effect of time of treatment on these regional BMD measurements. There was no change in trabecular bone score over the course of treatment. Conclusion: Treatment with burosumab is associated with a marked improvement in BMD, particularly in the hip. Since the hip is a frequent site of fracture in XLH, the effect of burosumab at this site is of considerable clinical relevance. The lack of an effect on TBS may relate to the fact that this measurement is much less sensitive to therapeutic interventions than BMD assessed by DXA. References: [1] JBMR. 2019. https://doi.org/10.1002/jbmr.3843.

High-dose vitamin D supplementation for cancer-treatment-induced bone loss in 164 breast and prostate cancer patients: A pooled analysis of two randomized controlled trials (RCTs).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 12105-12105
Author(s):  
Luke Joseph Peppone ◽  
Amber Kleckner ◽  
Julia Ellen Inglis ◽  
Jennifer E Reschke ◽  
Elizabeth Belcher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Bone Loss ◽  
Cancer Patients ◽  
Phase Iii ◽  
High Dose ◽  
Total Hip ◽  
Lower Baseline ◽  
Hip Bmd ◽  
Breast And Prostate Cancer

12105 Background: Aromatase Inhibitor (AI) therapy and androgen deprivation therapy (ADT) significantly accelerate bone loss and increase fracture risk. Vitamin D (VITD) protects against bone loss, but it is unclear whether the recommended daily allowance (RDA; 600 IU/day for ages 51-70) of VITD is sufficient for cancer patients. Data from two RCTs were pooled to examine the safety and efficacy of high-dose VITD versus the RDA of VITD on bone mineral density (BMD). Methods: 164 breast and prostate cancer patients on AIs and ADT, respectively, with low VITD (<32 ng/ml) were randomized to either high-dose VITD (50,000 IU/week; n=99) or placebo (n=65) for 24 weeks. All subjects received 600 IU/day of VITD. Of the 99 subjects assigned to high-dose VITD, 38 breast subjects also received the Exercise for Cancer Patients (EXCAP) program combining walking and resistance training. Serum VITD and calcium were assessed at weeks 0, 6, 12, 18, and 24. BMD was assessed at the hip and spine via DXA at weeks 0 and 24. The effect of high-dose VITD was tested via ANCOVA model adjusted for cancer type, baseline BMD and VITD. Results: High-dose VITD significantly reduced the amount of hip BMD loss versus the RDA of VITD (high-dose VITD: −0.8% vs placebo: −2.6%; p<0.01) over 24 weeks. Hip BMD loss was greater for subjects on ADT (high-dose VITD: −1.5% vs placebo: −4.1%; p=0.03) than subjects on AI therapy (high-dose VITD: −0.2% vs placebo: −1.7%; p=0.02). Among the high-dose VITD group, there was no BMD difference at the total hip between those who received EXCAP exercise vs no EXCAP (p=0.96). The largest differences in BMD were for those with lower baseline VITD levels (<27 ng/ml) for both total hip (high-dose VITD: −0.6% vs placebo: −3.2%; p<0.001) and femoral neck (high-dose VITD: +0.2% vs placebo: −2.4%; p=0.03). No between-group pooled differences were noted for total spine BMD (high-dose VITD: −0.2% vs placebo: −0.1%; p=0.82). High-dose VITD increased serum VITD without negatively affecting serum calcium (Table). Conclusions: High-dose VITD was safe and effective in significantly reducing hip BMD loss, with the largest benefit in those with lower baseline VITD levels. A phase III RCT is needed to confirm these findings. NCI Funding: K07 CA168911/R21 CA175793/UG1 CA189961/T32 CA102618 Clinical trial information: NCT02064946, NCT01419730 . [Table: see text]

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