Effect of zoledronic acid (Z) treatment based on serum parathyroid hormone (PTH) levels in patients (pts) with malignant bone disease

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8610-8610 ◽  
Author(s):  
A. Berruti ◽  
L. Dogliotti ◽  
M. Tampellini ◽  
A. Lipton ◽  
V. Hirsh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Bone Metastases ◽  
Solid Tumors ◽  
Bone Lesion ◽  
Small Subset ◽  
Prognostic Information ◽  
Risk Of Death ◽  
Increased Risk ◽  
Serum Pth

8610 Background: Z prevents skeletal-related events (SREs) in pts with bone metastases or multiple myeloma. However, secondary hyperparathyroidism and increased PTH may stimulate osteoclast activity and tumor growth, thus potentially limiting the efficacy of Z. Methods: Serum PTH was assessed at baseline and every 3 months in 1,068 pts enrolled in 3 randomized trials: 547 received Z, and 521 received placebo or pamidronate. Results: 213 (20%) pts had elevated PTH at baseline, and 105 of 547 (19%) pts had elevated PTH during Z treatment. In patients with normal baseline PTH, Z significantly reduced the incidence of SREs and delayed time to first SRE compared with control, whereas the risk of SREs was not reduced in patients with elevated baseline PTH. In prostate cancer patients, Z significantly decreased the risk of death compared with placebo in pts with normal baseline PTH (relative risk [RR] = 0.72; 95% confidence interval [CI]: 0.55, 0.94; P = .015). No survival advantage was observed in this subpopulation among pts with lung cancer or other solid tumors. In the small subset of pts with elevated PTH during Z treatment, there was an increased risk of death (for breast cancer pts, RR = 1.68 [95% CI: 1.10, 2.56]; P = .016; for prostate cancer pts, RR = 2.92 [95% CI: 1.83, 4.67]; P < .001). Additionally, elevated PTH during Z treatment in prostate cancer pts also significantly correlated with an increased risk of bone lesion progression (RR = 1.54 [95% CI: 1.09, 2.17]; P = .015). Elevated PTH during treatment did not affect the incidence or time to onset of SREs. Among pts with lung cancer or other solid tumors, elevated PTH during Z treatment did not provide any predictive or prognostic information. Conclusions: PTH levels either at baseline or during Z treatment appear to correlate with disease progression and the clinical benefit of Z in pts with bone metastases from certain types of cancer. This retrospective analysis suggests the importance of PTH status in patients undergoing Z treatment. Normalization of PTH levels may increase the benefit of Z. [Table: see text]

Predictors of clinical outcome in patients with bone metastases from prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4555-4555
Author(s):  
F. Saad ◽  
R. E. Coleman ◽  
R. Cook ◽  
M. R. Smith ◽  
J. E. Brown ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Clinical Outcome ◽  
Bone Metastases ◽  
Bone Markers ◽  
Bone Lesion ◽  
Bone Marker ◽  
Risk Of Death ◽  
Pathologic Fractures ◽  
Increased Risk

4555 Background: Bone metastases are a significant cause of morbidity in patients with prostate cancer (PC). To assess the predictive value of bone markers and fractures for clinical outcome in patients with bone metastases from PC, we conducted a retrospective analysis of patients in a large, randomized, controlled trial of zoledronic acid. Methods: Data were analyzed in patients treated with 4 mg zoledronic acid or placebo who had bone marker (n = 411) or fracture (n = 640) information. Cox regression models, adjusted for treatment group, were used to assess the association between bone markers (urinary N-telopeptide [NTX] and bone alkaline phosphatase [BALP]) or fractures (time-dependent variable) and the risk of death or of experiencing a first skeletal-related event (SRE) on study. For bone marker analyses, patients were grouped by low (< 50 nmol/mmol creatinine), moderate (50 to 99), or high (≥ 100) NTX levels and by low (< 146 U/L) or high (≥ 146) BALP. Results: Patients who experienced a fracture on study (19%) had shorter survival compared with patients who did not; the hazard ratio for death was 1.29 (95% CI = 1.01, 1.65; P = .04), suggesting 29% increased risk of death among these patients. When adjusted for previous SRE and baseline ECOG performance status ≥ 2, the risk for death associated with fractures was increased by 23% and trended toward statistical significance (P = .10). Patients with high NTX levels had significantly increased risk of SREs and disease progression (P < .001) compared with patients with low NTX. Relative to low NTX levels, high and moderate NTX levels were associated with a 5.72-fold (95% CI = 4.04, 8.11; P < .001) and 4.10-fold (95% CI = 2.81, 5.97; P < .001) increased risk of death, respectively. High BALP also significantly correlated with an increased risk of a first on-study SRE (P = .028) and bone lesion progression (P < .001). Conclusions: These analyses suggest that pathologic fractures are associated with increased risk if death and that high bone marker levels are associated with increased risk of SREs, bone lesion progression, and shorter survival in patients with PC and bone metastases. The results support appropriate treatment for the prevention of fractures and to decrease bone marker levels. [Table: see text]

scholarly journals Management of skeletal-related events in patients with advanced prostate cancer and bone metastases: Incorporating new agents into clinical practice

2012 ◽  
Vol 6 (6) ◽  
pp. 465 ◽  
Author(s):  
Alan So ◽  
Joseph Chin ◽  
Neil Fleshner ◽  
Fred Saad
Keyword(s):  
Prostate Cancer ◽  
Targeted Therapy ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Therapy Monitoring ◽  
Standard Of Care ◽  
Negative Consequences ◽  
Risk Of Death ◽  
Increased Risk ◽  
Skeletal Related Events

Skeletal-related events (SREs) are a common complication of bone metastases, and have serious negative consequences for patients with castrate-resistant prostate cancer (CRPC). SREs can lead to severe pain, increased risk of death, increased health care costs and reduced quality of life. Until recently, zoledronic acid has been the sole standard of care for the prevention of SREs in men with CRPC with bone metastases. Denosumab, a receptor activator of nuclear factor kappa-B ligand (RANK-L) inhibitor, has been recently approved for use in Canada for this indication, thus presenting another option for these patients. Denosumab was shown to be superior to zoledronic acid in delaying the time to first or subsequent SREs in CRPC patients with bone metastases. This review discusses current and previous trials examining agents designed to prevent SREs in men with CRPC and bone metastases. It also discusses the practical aspects of administering a bone-targeted therapy, including choosing a bone-targeted therapy, monitoring at the onset and during therapy, switching from one therapy to another, and assessing potential complications.

Public health impact of PSA doubling time after radical prostatectomy on prostate cancer specific and overall survival

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4568-4568
Author(s):  
S. J. Freedland ◽  
E. B. Humphreys ◽  
L. A. Mangold ◽  
M. Eisenberger ◽  
D. J. George ◽  
...  
Keyword(s):  
Public Health ◽  
Prostate Cancer ◽  
Radical Prostatectomy ◽  
Doubling Time ◽  
Health Concern ◽  
Small Subset ◽  
Risk Of Death ◽  
Psa Doubling Time ◽  
Increased Risk ◽  
Psa Recurrence

4568 Background: Among patients treated with radical prostatectomy (RP) with a PSA recurrence, we previously found men with a PSA doubling time (PSADT) <3 months were at increased risk of prostate cancer death, though these men constituted a small subset of patients. We sought to determine the actual and predicted number of prostate cancer deaths stratified by PSADT. Methods: We retrospectively studied 379 men treated with RP between 1982 and 2000 with a PSA recurrence. We calculated the actual and 15-year actuarial number of prostate cancer deaths in each of the following PSADT categories: <3, 3.0–8.9, 9.0–14.9, and ≥15.0 months. Results: Median follow-up after PSA recurrence was 7 years. During this time, there were 76 prostate cancer deaths; the majority (51%) were among men with a PSADT of 3.0–8.9 months. Though men with a PSADT <3 months were at the greatest risk of death, this group accounted for only 20% (n=15) of all prostate cancer deaths. Using actuarial 15-year estimates of prostate cancer specific survival, 50% of all prostate cancer deaths were among men with a PSADT of 3.0–8.9 months while men with a PSADT <3 months accounted for only 13% of prostate cancer deaths. Using actuarial 15-year estimates of all-cause and prostate cancer specific mortality, among men with a PSADT <15 months, prostate cancer was estimated to be the cause of death in 94% (145/155). Only among men with a PSADT >15 months was the risk of competing causes of mortality high enough such that the majority of deaths were not attributed to prostate cancer. Conclusions: Among a select cohort of men treated with RP who experienced a PSA recurrence, prostate cancer was estimated to account for 75% of all deaths. Though men with a PSADT <3 months were at the greatest risk, the majority of deaths occurred among men with a PSADT of 3.0–8.9 months. Efforts to reduce prostate cancer mortality should focus on men with intermediate PSADT times (3.0–15.0 months) as they represent the greatest public health concern among men with PSA recurrence following RP. [Table: see text] No significant financial relationships to disclose.

Zoledronic Acid Versus Placebo in the Treatment of Skeletal Metastases in Patients With Lung Cancer and Other Solid Tumors: A Phase III, Double-Blind, Randomized Trial—The Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group

2003 ◽  
Vol 21 (16) ◽  
pp. 3150-3157 ◽  
Author(s):  
Lee S. Rosen ◽  
David Gordon ◽  
Simon Tchekmedyian ◽  
Ronald Yanagihara ◽  
Vera Hirsh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Placebo Group ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Solid Tumors ◽  
Phase Iii ◽  
Morbidity Rate ◽  
Skeletal Metastases ◽  
Event Analysis

Purpose: To assess the efficacy and safety of zoledronic acid in patients with bone metastases secondary to solid tumors other than breast or prostate cancer. Patients and Methods: Patients were randomly assigned to receive zoledronic acid (4 or 8 mg) or placebo every 3 weeks for 9 months, with concomitant antineoplastic therapy. The 8-mg dose was reduced to 4 mg (8/4-mg group). The primary efficacy analysis was proportion of patients with at least one skeletal-related event (SRE), defined as pathologic fracture, spinal cord compression, radiation therapy to bone, and surgery to bone. Secondary analyses (time to first SRE, skeletal morbidity rate, and multiple event analysis) counted hypercalcemia as an SRE. Results: Among 773 patients with bone metastases from lung cancer or other solid tumors, the proportion with an SRE was reduced in both zoledronic acid groups compared with the placebo group (38% for 4 mg and 35% for 8/4 mg zoledronic acid v 44% for the placebo group; P = .127 and P = .023 for 4-mg and 8/4-mg groups, respectively). Additionally, 4 mg zoledronic acid significantly increased time to first event (median, 230 v 163 days for placebo; P = .023), an important end point in this poor-prognosis population, and significantly reduced the risk of developing skeletal events by multiple event analysis (hazard ratio = 0.732; P = .017). Zoledronic acid was well tolerated; the most common adverse events in all treatment groups included bone pain, nausea, anemia, and vomiting. Conclusion: Zoledronic acid (4 mg infused over 15 minutes) is the first bisphosphonate to reduce skeletal complications in patients with bone metastases from solid tumors other than breast and prostate cancer.

Effect of the number of bone lesions on efficacy of zoledronic acid for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8529-8529 ◽  
Author(s):  
N. Shirina ◽  
R. E. Coleman ◽  
Y. M. Chen
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Lung Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Morbidity Rate ◽  
Bone Lesions ◽  
The Mean

8529 Background: It has been postulated that greater numbers of bone metastases and thus greater tumor burden may lead to increased skeletal morbidity. To assess the effect that the number of baseline bone metastases may have on the efficacy of zoledronic acid in patients with solid tumors, we conducted a retrospective analysis of 3 large, randomized, controlled trials. Methods: Data were evaluated from the intent-to-treat population with breast cancer (n = 739), prostate cancer (n = 397), or lung cancer and other solid tumors (n = 480) who were treated with zoledronic acid 4 mg, pamidronate 90 mg, or placebo and had information available on number of baseline bone lesions. Patients were stratified into 2 groups: those with ≤ 3 bone lesions or > 3 lesions. Results: In general, patients with > 3 lesions had a higher skeletal morbidity rate (SMR) compared with patients with ≤ 3 lesions (Table 1), and zoledronic acid reduced SREs regardless of the number of bone lesions, but the benefit of zoledronic acid appeared greater in patients with > 3 lesions. In patients with lung cancer and other solid tumors who had > 3 bone lesions, zoledronic acid significantly reduced the mean SMR (P = .008) and significantly prolonged time to first SRE (median, 171 vs 84 day; P = .005) compared with placebo. In prostate cancer patients with > 3 bone lesions, zoledronic acid also significantly reduced the mean SMR compared with placebo (Table 1). In breast cancer patients with > 3 bone lesions, the mean SMRs were similar for zoledronic acid and pamidronate groups (Table 1). Conclusions: Patients with a greater number of bone lesions are at higher risk for skeletal complications and receive greater clinical benefit from treatment with zoledronic acid. [Table: see text] [Table: see text]

scholarly journals Improved Prognostic Stratification Using Circulating Tumor Cell Clusters in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 268 ◽  
Author(s):  
Chun Wang ◽  
Zhenchao Zhang ◽  
Weelic Chong ◽  
Rui Luo ◽  
Ronald E. Myers ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Circulating Tumor Cell ◽  
Castration Resistant Prostate Cancer ◽  
Prognostic Information ◽  
Cox Models ◽  
Risk Of Death ◽  
Castration Resistant ◽  
Increased Risk ◽  
Prognostic Stratification

Liquid biopsy-based biomarkers have advantages in monitoring the dynamics of metastatic castration-resistant prostate cancer (mCRPC), a bone-predominant metastatic disease. Previous studies have demonstrated associations between circulating tumor cells (CTCs) and clinical outcomes of mCRPC patients, but little is known about the prognostic value of CTC-clusters. In 227 longitudinally collected blood samples from 64 mCRPC patients, CTCs and CTC-clusters were enumerated using the CellSearch platform. The associations of CTC and CTC-cluster counts with progression-free survival (PFS) and overall survival (OS), individually and jointly, were evaluated by Cox models. CTCs and CTC-clusters were detected in 24 (37.5%) and 8 (12.5%) of 64 baseline samples, and in 119 (52.4%) and 27 (11.9%) of 227 longitudinal samples, respectively. CTC counts were associated with both PFS and OS, but CTC-clusters were only independently associated with an increased risk of death. Among patients with unfavorable CTCs (≥5), the presence of CTC-clusters signified a worse survival (log-rank p = 0.0185). mCRPC patients with both unfavorable CTCs and CTC-clusters had the highest risk for death (adjusted hazard ratio 19.84, p = 0.0072), as compared to those with <5 CTCs. Analyses using longitudinal data yielded similar results. In conclusion, CTC-clusters provided additional prognostic information for further stratifying death risk among patients with unfavorable CTCs.

scholarly journals Retrospective Toxicological Profiling of Radium-223 Dichloride for the Treatment of Bone Metastases in Prostate Cancer Using Adverse Event Data

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 149 ◽  
Author(s):  
Theodoros G. Soldatos ◽  
Ioannis Iakovou ◽  
Christos Sachpekidis
Keyword(s):  
Prostate Cancer ◽  
Adverse Event ◽  
Bone Metastases ◽  
Cancer Patients ◽  
Safety Profile ◽  
Adverse Event Reporting System ◽  
Castration Resistant Prostate Cancer ◽  
Risk Of Death ◽  
Radium 223 ◽  
Increased Risk

Background and Objective: Radium-223 dichloride (Xofigo®) is a calcium mimetic agent approved for the treatment of castration-resistant prostate cancer patients with symptomatic bone metastases and no known visceral metastatic disease. This targeted, α-particle-emitting therapy has demonstrated significant survival benefit accompanied by a favorable safety profile. Nevertheless, recent evidence suggests that its combined use with abiraterone and prednisone/prednisolone may be associated with increased risk of death and fractures. While the precise pathophysiologic mechanisms of these events are not yet clear, collecting evidence from more clinical trials and translational studies is necessary. The aim of our present study is to assess whether accessible sources of patient outcome data can help gain additional clinical insights to radium-223 dichloride’s safety profile. Materials and Methods: We performed a retrospective analysis of cases extracted from the FDA Adverse Event Reporting System and characterized side effect occurrence by using reporting ratios. Results: A total of ~1500 prostate cancer patients treated with radium-223 dichloride was identified, and side effects reported with the use of radium-223 dichloride alone or in combination with other therapeutic agents were extracted. Our analysis demonstrates that radium-223 dichloride may often come with hematological-related reactions, and that, when administered together with other drugs, its safety profile may differ. Conclusions: While more prospective studies are needed to fully characterize the toxicological profile of radium-223 dichloride, the present work constitutes perhaps the first effort to examine its safety when administered alone and in combination with other agents based on computational evidence from public real-world post marketing data.

Correlation of N-telopeptide of type I collagen (NTX) with survival and fractures in patients (pts) with bone metastases from renal cell carcinoma (RCC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16016-e16016
Author(s):  
J. E. Brown ◽  
A. Lipton ◽  
R. J. Cook ◽  
D. Michaelson ◽  
R. E. Coleman ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Solid Tumors ◽  
Prognostic Significance ◽  
Small Sample ◽  
Phase Iii ◽  
Bone Lesions ◽  
Type I ◽  
Risk Of Death ◽  
Pathologic Fractures ◽  
Increased Risk

e16016 Background: The osteolysis marker NTX has shown prognostic significance in pts with bone metastases from a broad range of solid tumors, but its potential in pts with RCC has not been investigated. Methods: This was an exploratory correlative analysis of NTX levels and outcomes in the RCC subset of pts treated with zoledronic acid (ZOL) in a 21-month phase III trial (Rosen et al. J Clin Oncol. 2002). In North American pts in this study, urinary NTX was measured approximately every 3 mo and was expressed per mmol creatinine (CR). Endpoints included overall survival (OS), disease progression in bone, and pathologic fractures. Relative risks and 95% confidence intervals for pts with elevated NTX (NTX ≥ 64 nmol/mmol CR) versus normal NTX (< 64 nmol/mmol CR) were calculated by Cox regression for baseline and most recent (≤ 6 mo prior) NTX assessments. Results: Among 55 ZOL-treated RCC pts, 29 had baseline NTX data (median = 60 nmol/mmol CR). Whereas baseline NTX levels showed trends for outcomes, recent NTX levels profoundly correlated with outcomes ( Table ). An elevated recent NTX measurement correlated with a > 13-fold increased risk of death and a > 11-fold increased risk of progression in bone. Correlations were also significant for first and all on-study fractures. Conclusions: In pts with RCC receiving ZOL, serial NTX assessments may provide important prognostic insight. Although based on a small sample size, correlations between recent NTX levels and outcomes in RCC pts are more profound than those previously reported in pts with other solid tumors (Brown et al. J Natl Cancer Inst. 2005). Elevated NTX could alert physicians to the need to more closely monitor bone lesions and intervene to prevent fractures in RCC pts. This may be especially important in the context of new systemic therapies that are improving the outlook in the advanced RCC setting. [Table: see text] [Table: see text]

Sign in / Sign up

Export Citation Format

Share Document