-
Neurosurgical Focus Jan 2017OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE With the advent of new adjunctive therapy, the overall survival of patients harboring spinal column tumors has improved. However, there is limited knowledge regarding the optimal bone graft options following resection of spinal column tumors, due to their relative rarity and because fusion outcomes in this cohort are affected by various factors, such as radiation therapy (RT) and chemotherapy. Furthermore, bone graft options are often limited following tumor resection because the use of local bone grafts and bone morphogenetic proteins (BMPs) are usually avoided in light of microscopic infiltration of tumors into local bone and potential carcinogenicity of BMP. The objective of this study was to review and meta-analyze the relevant clinical literature to provide further clinical insight regarding bone graft options. METHODS A web-based MEDLINE search was conducted in accordance with preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, which yielded 27 articles with 383 patients. Information on baseline characteristics, tumor histology, adjunctive treatments, reconstruction methods, bone graft options, fusion rates, and time to fusion were collected. Pooled fusion rates (PFRs) and I values were calculated in meta-analysis. Meta-regression analyses were also performed if each variable appeared to affect fusion outcomes. Furthermore, data on 272 individual patients were available, which were additionally reviewed and statistically analyzed. RESULTS Overall, fusion rates varied widely from 36.0% to 100.0% due to both inter- and intrastudy heterogeneity, with a PFR of 85.7% (I = 36.4). The studies in which cages were filled with morselized iliac crest autogenic bone graft (ICABG) and/or other bone graft options were used for anterior fusion showed a significantly higher PFR of 92.8, compared with the other studies (83.3%, p = 0.04). In per-patient analysis, anterior plus posterior fusion resulted in a higher fusion rate than anterior fusion only (98.8% vs 86.4%, p < 0.001). Although unmodifiable, RT (90.3% vs 98.6%, p = 0.03) and lumbosacral tumors (74.6% vs 97.9%, p < 0.001) were associated with lower fusion rates in univariate analysis. The mean time to fusion was 5.4 ± 1.4 months (range 3-9 months), whereas 16 of 272 patients died before the confirmation of solid fusion with a mean survival of 3.1 ± 2.1 months (range 0.5-6 months). The average time to fusion of patients who received RT and chemotherapy were significantly longer than those who did not receive these adjunctive treatments (RT: 6.1 months vs 4.3 months, p < 0.001; chemotherapy: 6.0 months vs 4.3 months, p = 0.02). CONCLUSIONS Due to inter- and intrastudy heterogeneity in patient, disease, fusion criteria, and treatment characteristics, the optimal surgical techniques and factors predictive of fusion remain unclear. Clearly, future prospective, randomized studies will be necessary to better understand the issues surrounding bone graft selection following resection of spinal column tumors.
Topics: Bone Transplantation; Humans; Spinal Cord Neoplasms; Spinal Fusion; Spinal Neoplasms
PubMed: 28041327
DOI: 10.3171/2016.8.FOCUS16112 -
The Cochrane Database of Systematic... Dec 2017The prevalence and incidence of pain and skeletal complications of metastatic bone disease such as pathologic fractures, spinal cord compression and hypercalcemia is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prevalence and incidence of pain and skeletal complications of metastatic bone disease such as pathologic fractures, spinal cord compression and hypercalcemia is high and an important contributor to morbidity, poor performance status and decreased quality of life. Moreover, pathologic fractures are associated with increased risk of death in people with disseminated malignancies. Therefore, prevention of pain and fractures are important goals in men with prostate cancer at risk for skeletal complications.
OBJECTIVES
To assess the effects of bisphosphonates in men with bone metastases from prostate cancer.
SEARCH METHODS
We identified studies by electronic search of bibliographic databases including the Cochrane Controlled Trials Register and MEDLINE on 13 July 2017 and trial registries. We handsearched the Proceedings of American Society of Clinical Oncology (to July 2017) and reference lists of all eligible trials identified. This is an update of a review last published in 2006.
SELECTION CRITERIA
We included randomized controlled studies comparing the effectiveness of bisphosphonates in men with bone metastases from prostate cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the quality of trials. We defined the proportion of participants with pain response as the primary end point; secondary outcomes were skeletal-related events, mortality, quality of life, adverse events, analgesic consumption and disease progression. We assessed the quality of the evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
We included 18 trials reporting on 4843 participants comparing the effect of bisphosphonate administration to control regimens.
PRIMARY OUTCOME
there was no clear difference in the proportion of participants with pain response (RR 1.15, 95% CI 0.93 to 1.43; P = 0.20; I = 0%; 3 trials; 876 participants; low quality evidence). In absolute terms, bisphosphonates resulted in a pain response in 40 more participants per 1000 (19 fewer to 114 more).
SECONDARY OUTCOMES
bisphosphonates probably reduced the incidence of skeletal-related events in participants with prostate cancer metastatic to bone (RR 0.87, 95% CI 0.81 to 0.94; P = 0.27; I = 19%; 9 trials; 3153 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 58 fewer SREs per 1000 (85 fewer to 27 fewer).We found no clinically relevant differences in mortality (RR 0.97, 95% CI 0.91 to 1.04; P = 0.43; I = 1%; 9 trials; 2450 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 16 fewer deaths per 1000 (47 fewer to 21 more).Outcome definition of quality of life and the measurement tools varied greatly across trials and we were unable to extract any quantitative data for meta-analysis.Bisphosphonates probably increased the number of participants affected by nausea (RR 1.19, 95% CI 1.00 to 1.41; P = 0.05; I = 0%; 9 trials; 3008 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in seven more cases of nausea per 1000 (0 fewer to 14 more). Bisphosphonates probably increased the number of renal adverse events (RR 1.65, 95% CI 1.11 to 2.46; P = 0.01; I = 0%; 7 trials; 1794 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 22 more renal adverse events per 1000 (4 more to 50 more). We found no clear difference in the number of participants with osteonecrosis of the jaw between groups (RR 1.92, 95% CI 0.75 to 4.90; P = 0.17; I = 0%; 5 trials; 1626 participants; very low quality evidence). In absolute terms, bisphosphonates resulted in seven more cases with osteonecrosis of the jaw per 1000 (2 fewer to 29 more). We observed no clinically relevant difference in the proportion of participants with decreased analgesic consumption (RR 1.19, 95% CI 0.87 to 1.63; P = 0.28; I = 37%; 4 trials; 416 participants). Statistical analysis revealed that bisphosphonates probably reduced the number of participants with disease progression (RR 0.94, 95% CI 0.90 to 0.98; P = 0.006; I = 0%; 7 trials; 2115 participants; moderate quality evidence). In absolute terms, bisphosphonates resulted in 36 fewer cases of disease progression per 1000 (71 fewer to 7 fewer).Findings of our predefined subgroup and sensitivity analyses were no different from those of the primary analyses.
AUTHORS' CONCLUSIONS
Based on low quality evidence, there may be no clinically relevant difference in the proportion of men with pain response between bisphosphonates and control regimens in men with bone metastases from prostate cancer. Bisphosphonates probably decrease the number of skeletal-related events and disease progression. These benefits need to be weighed against the increased risk of renal impairment and nausea in men receiving bisphosphonates. Future studies should explicitly evaluate patient important outcomes such as quality of life and pain by using standardized and comparable assessment tools.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Bone Neoplasms; Diphosphonates; Humans; Kidney; Male; Nausea; Pain; Prostatic Neoplasms; Randomized Controlled Trials as Topic
PubMed: 29278410
DOI: 10.1002/14651858.CD006250.pub2 -
Journal of Neuroimaging : Official... Mar 2022To comprehensively summarize the characteristics of radiological findings of laryngeal conventional chondrosarcomas. (Review)
Review
BACKGROUND AND PURPOSE
To comprehensively summarize the characteristics of radiological findings of laryngeal conventional chondrosarcomas.
METHODS
We included patients with pathologically proven laryngeal conventional chondrosarcomas with CT and /or MRI, including 41 cases from 31 publications recruited after a systematic review and 14 cases from our institution. Two board-certified radiologists reviewed and evaluated all the radiological images. The relationship between pathological grade and radiological findings was analyzed.
RESULTS
The median long diameter of the lesion was 3.1 cm (range, 1.5-8.5 cm). The most common location was the cricoid (74.5%), followed by the thyroid (12.7%), cricoid and thyroid (7.3%), and arytenoid (5.5%). All lesions showed well-defined margins. Cortical defect/expansion (98.0%), internal low density (89.6%), and calcification (95.8%) with homogeneous and scarce contrast enhancement on contrast-enhanced CT (85.3%) were frequently observed. All cases showed high signal on T2-weighted imaging, low signal on T1-weighted imaging (T1WI), and heterogeneous and mild contrast enhancement on postcontrast T1WI. No significant differences were found between the pathological grades and radiological findings.
CONCLUSIONS
In our summary of comprehensive CT and MRI findings of laryngeal conventional chondrosarcomas, we found that the knowledge of these radiological features may facilitate prompt diagnosis and appropriate management.
Topics: Bone Neoplasms; Chondrosarcoma; Humans; Magnetic Resonance Imaging; Radiography; Retrospective Studies
PubMed: 35019171
DOI: 10.1111/jon.12963 -
Neurosurgical Focus Aug 2016OBJECTIVE The aim of this study was to systematically review the literature on reported outcomes following decompression surgery for spinal metastases. METHODS The... (Review)
Review
OBJECTIVE The aim of this study was to systematically review the literature on reported outcomes following decompression surgery for spinal metastases. METHODS The authors conducted MEDLINE, Scopus, and Web of Science database searches for studies reporting clinical outcomes and complications associated with decompression surgery for metastatic spinal tumors. Both retrospective and prospective studies were included. After meeting inclusion criteria, articles were categorized based on the following reported outcomes: survival, ambulation, surgical technique, neurological function, primary tumor histology, and miscellaneous outcomes. RESULTS Of the 4148 articles retrieved from databases, 36 met inclusion criteria. Of those included, 8 were prospective studies and 28 were retrospective studies. The year of publication ranged from 1992 to 2015. Study size ranged from 21 to 711 patients. Three studies found that good preoperative Karnofsky Performance Status (KPS ≥ 80%) was a significant predictor of survival. No study reported a significant effect of time-to-surgery following the onset of spinal cord compression symptoms on survival. Three studies reported improvement in neurological function following surgery. The most commonly cited complication was wound infection or dehiscence (22 studies). Eight studies reported that preoperative ambulatory or preoperative motor status was a significant predictor of postoperative ambulatory status. A wide variety of surgical techniques were reported: posterior decompression and stabilization, posterior decompression without stabilization, and posterior decompression with total or subtotal tumor resection. Although a wide range of functional scales were used to assess neurological outcomes, four studies used the American Spinal Injury Association (ASIA) Impairment Scale to assess neurological function. Four studies reported the effects of radiation therapy and local disease control for spinal metastases. Two studies reported that the type of treatment was not significantly associated with the rate of local control. The most commonly reported primary tumor types included lung cancer, prostate cancer, breast cancer, renal cancer, and gastrointestinal cancer. CONCLUSIONS This study reports a systematic review of the literature on decompression surgery for spinal metastases. The results of this study can help educate surgeons on the previously published predictors of outcomes following decompression surgery for metastatic spinal disease. However, the authors also identify significant gaps in the literature and the need for future studies investigating the optimal practice with regard to decompression surgery for spinal metastases.
Topics: Decompression, Surgical; Humans; Postoperative Complications; Prospective Studies; Retrospective Studies; Spinal Cord Compression; Spinal Neoplasms; Survival Rate; Treatment Outcome
PubMed: 27476844
DOI: 10.3171/2016.6.FOCUS16166 -
International Journal of Clinical... Nov 2022Brain metastasis in sarcomas is associated with a poor prognosis. Data regarding prognostic factors and clinical outcomes of surgical resection of brain metastasis from...
BACKGROUND
Brain metastasis in sarcomas is associated with a poor prognosis. Data regarding prognostic factors and clinical outcomes of surgical resection of brain metastasis from sarcomas are limited. The objective of this systematic review was to evaluate survival outcomes post-brain metastasectomy for patients with soft tissue and bone sarcomas.
METHODS
A systematic review was conducted examining survival outcomes among adults and children with soft tissue and bone sarcoma undergoing brain metastasectomy, in the English language from inception up to May 31, 2021. Two reviewers independently evaluated and screened the literature, extracted the data, and graded the included studies. The body of evidence was evaluated and graded according to the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and the Joanna Briggs Institute Critical Appraisal Checklist for Case Series. Results were synthesized using descriptive methods. A meta-analysis was not possible due to the low quality and heterogeneity of studies.
RESULTS
Ten studies published between 1994 and 2020 were included: three were retrospective cohort studies and seven were case series. 507 patients were included, of whom 269 underwent brain metastasectomy. The median follow-up period ranged between 14 and 29 months. The median survival period after metastasectomy ranged from 7 to 25 months. The most common prognostic factors associated with survival included presenting performance status, age, number of brain metastases, presence of lung metastases, and peri-operative radiation therapy administration.
DISCUSSION
Although the level of evidence is low, retrospective studies support that brain metastasectomy can be performed with reasonable post-operative survival in selected individuals.
Topics: Adult; Child; Humans; Metastasectomy; Retrospective Studies; Osteosarcoma; Sarcoma; Soft Tissue Neoplasms; Bone Neoplasms; Lung Neoplasms; Brain; Brain Neoplasms; Prognosis; Survival Rate
PubMed: 35994183
DOI: 10.1007/s10147-022-02227-4 -
Skeletal Radiology Aug 2019To review the efficacy of percutaneous thermal ablation (TA) of bone metastases (radiofrequency ablation [RFA], microwave ablation [MWA], cryoablation [CA], and... (Review)
Review
OBJECTIVE
To review the efficacy of percutaneous thermal ablation (TA) of bone metastases (radiofrequency ablation [RFA], microwave ablation [MWA], cryoablation [CA], and MR-guided focused ultrasound [MRgFUS]) in reducing pain in patients with advanced stage cancer.
MATERIALS AND METHODS
We searched MEDLINE/PubMed, MEDLINE In-Process, BIDS ISI, Embase, CINAHL, and the Cochrane database using the keywords "ablation," "painful," "bone," and "metastases" combined in multiple algorithms. Inclusion criteria were: original clinical studies published between 2001 and 2018; performance of RFA, MWA, CA or MRgFUS; and quantitative pain assessment before/after TA of bone metastasis.
RESULTS
Eleven papers (3 on RFA, 1 on MWA, 2 on CA, and 5 on MRgFUS) involving 364 patients were reviewed. A technical success rate of 96-100% was reported, with follow-up for up to 6 months. At baseline, pain scores ranged from 5.4 to 8, at 1-4 weeks from 0.5 to 5, and at 12 weeks from 0.3 to 4.5. Mean pain reduction compared with baseline ranged from 26 to 91% at 4 weeks and from 16% to 95% at 12 weeks. MWA treatments caused no complications, whereas MRgFUS showed the highest complication rate. The number of minor complications observed ranged from 0 to 59 (complication ratio 0-1.17), whereas the number of significant adverse effects ranged from 0 to 4 (complication ratio 0-0.04).
CONCLUSION
All techniques achieved pain relief after 1 and 3 months, in up to 91% and 95% of patients respectively. MWA showed a negligible complication rate, whereas MRgFUS is associated with a noteworthy rate of adverse events. Future studies should adopt a standardized pain reporting scale to allow for meta-analysis.
Topics: Ablation Techniques; Bone Neoplasms; Cancer Pain; Humans; Musculoskeletal Pain
PubMed: 30627778
DOI: 10.1007/s00256-018-3140-0 -
Pediatric Blood & Cancer Sep 2015Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to summarize the literature describing QOL in this population and differences in QOL based on local control procedures.
PROCEDURE
Included studies described ≥5 patients <25 years old who had completed local control treatment for bone sarcoma, defined QOL as a main outcome, and measured it with a validated instrument. Data extraction and quality assessments were conducted with standardized tools. Meta-analyses compared QOL based on surgical procedure (limb-sparing vs. amputation) and were stratified by assessment type (objective physical function, clinician-assessed disability, patient-reported disability, and patient-reported QOL). Effect sizes were reported as the standard mean difference when multiple instruments were used within a comparison and weighted mean difference otherwise. All were weighted by inverse variance and modeled with random effects.
RESULTS
Twenty-two of 452 unique manuscripts were included in qualitative syntheses, eight of which were included in meta-analyses. Manuscripts were heterogeneous with respect to included patient populations (age, tumor type, time since treatment) and QOL instruments. Prospective studies suggested that QOL improves over time, and that female sex and older age at diagnosis are associated with poor QOL. Meta-analyses showed no differences in outcomes between patients who underwent limb-sparing versus amputation for local control.
CONCLUSION
QOL studies among children and AYAs with bone sarcoma are remarkably diverse, making it difficult to detect trends in patient outcomes. Future research should focus on standardized QOL instruments and interpretations.
Topics: Adolescent; Age Factors; Amputation, Surgical; Bone Neoplasms; Child; Child, Preschool; Cross-Sectional Studies; Disabled Persons; Female; Humans; Limb Salvage; Male; Prospective Studies; Quality of Life; Recovery of Function; Sarcoma; Self Report; Surveys and Questionnaires; Survivors; Young Adult
PubMed: 25820683
DOI: 10.1002/pbc.25514 -
Journal of Orthopaedic Surgery and... Oct 2021Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Osteosarcoma is the most prevalent malignant osseous sarcoma in children and adolescents, whose prognosis is still relatively poor nowadays. Recent studies have shown the critical function and potential clinical applications of circular RNAs (circRNAs) in osteosarcoma. Our review aimed to perform an updated meta-analysis to explore their clinicopathologic significance and prognostic value.
METHODS
The structured literature was conducted via eight electronic databases and four gray literature sources until 20 Feb 2021 to identify eligible studies. The data was extracted directly from the articles or reconstructed based on Kaplan-Meier curves. The Newcastle-Ottawa Scale (NOS) tool was used to assess study quality. The clinicopathologic significance of circRNAs was measured through odds ratios (ORs) and their 95% confidence intervals (CIs), while the prognostic value was evaluated through hazard ratios (HRs) and their 95% CIs of overall survival (OS) and disease-free survival (DFS). Heterogeneity and publication bias were assessed. Sensitivity analyses were conducted. Subgroup analyses were performed according to study characteristics. An additional analysis was performed to investigate the relation between circ_0002052 and osteosarcoma.
RESULTS
Fifty-two studies were identified, in which 38 on clinicopathologic features and 36 on survival prognosis were included in quantitative analysis. The overall study quality was moderate with a median NOS score of 5.5 stars (range 3 to 8). For clinicopathologic features, dysregulated circRNAs were related to larger tumor size (OR 2.122, 95%CI 1.418-3.175), advanced clinical stage (OR 2.847, 95%CI 2.059-3.935), and present of metastasis (OR 2.630, 95%CI 1.583-4.371). For chemotherapy, dysregulated circRNAs suggest a better response (OR 0.443, 95%CI 0.231-0.849), but a higher probability of resistance (OR 9.343, 95%CI 5.352-16.309). For survival prognosis, dysregulated circRNAs were significantly correlated with poor OS (HR 2.437, 95%CI 2.224-2.670) and DFS (HR 2.125, 95%CI 1.621-2.786). The results did not show differences among subgroups. Higher circ_0002052 expression showed a relation with poor OS (HR 3.197, 95%CI 2.054-4.976).
CONCLUSIONS
Our review demonstrated that abnormally expressed circRNAs have a relation with advanced clinicopathologic features and better response, but a higher probability of resistance and poor survival prognosis in osteosarcoma patients. However, more studies are encouraged to provide more robust evidence to translate circRNAs into clinical practice.
TRIAL REGISTRATION
PROSPERO ID: CRD42021235031.
Topics: Adolescent; Biomarkers, Tumor; Bone Neoplasms; Humans; Osteosarcoma; Prognosis; RNA, Circular
PubMed: 34620208
DOI: 10.1186/s13018-021-02568-2 -
European Review For Medical and... May 2021Approximately 50% of cancer patients develop bone metastases in their natural disease history. The management of metastatic bone disease requires a multidisciplinary...
OBJECTIVE
Approximately 50% of cancer patients develop bone metastases in their natural disease history. The management of metastatic bone disease requires a multidisciplinary approach. Both radiofrequency ablation (RFA) and radiation therapy (RT) were safe and effective in the management of painful metastases, even if they rely on totally different action mechanisms. A synergistic combination of RT and RFA seems to result in a better pain control. A systematic review was performed to describe the feasibility and effectiveness of the association between RFA and RT in the treatment of metastatic bone pain in oligo-metastatic patients, evaluating its role in alleviating bone pain, reducing the risk of fractures, and consequently ensuring a better quality of life.
MATERIALS AND METHODS
A systematic database search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review included studies that reported populations meeting the following inclusion criteria: (I) confirmed bone metastases in adult patients; (II) active bone metastases pain; (III) patients treated with combined RFA-RT; (IV) Original studies.
RESULTS
Three papers that evaluated the combined treatment with doses ranging from moderately hypofractionated three-dimensional conformal RT (3D-CRT) and stereotactic body radiation therapy (SBRT) schedules were selected.
CONCLUSIONS
The RFA-RT combined strategy appears to be promising in terms of efficiency and safety with adequate pain control and quality of life improvement. Positive effects on time to local failure and overall survival increase were also observed. Further prospective studies are needed to better delineate RFA-RT treatment benefits.
Topics: Bone Neoplasms; Cancer Pain; Combined Modality Therapy; Fractures, Bone; Humans; Radiation Dose Hypofractionation; Radiofrequency Ablation; Radiosurgery
PubMed: 34109573
DOI: 10.26355/eurrev_202105_25930 -
British Journal of Clinical Pharmacology Sep 2014The objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody... (Review)
Review
AIM
The objective of this systematic review was to characterize the pharmacokinetics and pharmacodynamics of denosumab (XGEVA®), a fully human IgG2 monoclonal antibody which binds to receptor activator of nuclear factor kappa-B ligand (RANKL), for the treatment of skeletal-related events (SREs) in patients with advanced cancer and bone metastases.
METHODS
A total of 708 patients (116 healthy patients and 592 patients with solid tumours or multiple myeloma and bone metastases) included in seven clinical studies were evaluated for denosumab pharmacokinetics. Denosumab was administered as a single subcutaneous (s.c.) dose or multiple s.c. doses, ranging from 0.1 to 3.0 mg kg(-1) or 30 mg to 180 mg fixed dosing, every 1 or 3 months for up to 45 months.
RESULTS
Consistent with the results in healthy adults, single s.c. doses of denosumab demonstrated dose-dependent, non-linear pharmacokinetics in advanced cancer patients with bone metastases across a wide dose range (0.1-3.0 mg kg(-1) ). Reductions in levels of the bone turnover marker, uNTx/Cr, were observed within 1 day. The duration of reductions generally increased with dose and dosing frequency. In patients with solid tumours and bone metastases, pharmacokinetics and pharmacodynamic comparisons across tumour types and concomitant cancer therapies (chemotherapies and/or hormone therapies) suggest that neither tumour type nor type of concomitant therapy markedly affects denosumab pharmacokinetics or pharmacodynamics.
CONCLUSIONS
Denosumab displayed non-linear pharmacokinetics at doses below 60 mg but at higher doses, denosumab exposure increased approximately dose-proportionally in advanced cancer patients with bone metastases. Following a 120 mg, every 4 weeks dosing schedule, similar denosumab pharmacokinetics and pharmacodynamics were observed across tumour types and were independent of concomitant cancer therapies.
Topics: Adult; Antibodies, Monoclonal, Humanized; Bone Neoplasms; Denosumab; Dose-Response Relationship, Drug; Humans; Neoplasms; RANK Ligand
PubMed: 24548274
DOI: 10.1111/bcp.12355