Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013
Introduction: Androgen deprivation therapy (ADT) is a primary treatment option for patients diagnosed with locally advanced-stage or metastatic prostate cancer. Androgen deprivation can be achieved either by radical orchiectomy or by medical castration using a gonadotropin-releasing hormone agonist....
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doaj-2b9c5cc0921e49f6b39bc2b06bb72e2b2020-11-25T02:59:58ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2020-07-011010.3389/fonc.2020.01125535407Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013Zin W. Myint0Charles A. Kunos1Division of Medical Oncology, Department of Internal Medicine, University of Kentucky, Lexington, KY, United StatesCancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, United StatesIntroduction: Androgen deprivation therapy (ADT) is a primary treatment option for patients diagnosed with locally advanced-stage or metastatic prostate cancer. Androgen deprivation can be achieved either by radical orchiectomy or by medical castration using a gonadotropin-releasing hormone agonist. ADT has been linked to an initial 12-month loss of bone mineral density, a risk factor for weight-bearing bone fracture, and therefore, a confounding hazard for adverse event when patients are enrolled on early phase trials. To better understand the frequency of ADT-investigational agent-related bone fracture, we conducted a retrospective study of National Cancer Institute Cancer Therapy Evaluation Program (CTEP)-sponsored early phase trials to determine the number of fractures observed among enrolled prostate cancer patients.Patients and Methods: 464 locally advanced-stage or metastatic prostate cancer patients were identified among seven ADT-investigational agent trials conducted between 2006 and 2013. Demographic, co-morbidity, treatment, and adverse event variables were abstracted from CTEP databases and descriptive statistics were used.Results: 464 men had a median age of 64 years, were mostly white (90%), and had a performance status of 0 or 1 (98%). The number of new bone fractures occurring on or after ADT-investigational agent treatment was very low (4.6 per 1000 person-years). The median pretrial prostate specific antigen level was 29 ng/mL and most men (71%) had prostate cancer histopathology Gleason 7 score or higher. In these trials, 43 percent of men had bone only and 35 percent had bone and visceral metastatic disease. The most frequent grade 1 or 2 adverse events were fatigue (36%), hot flashes (27%), and anemia (17%). Grade 3 or higher adverse events were rare, with hypertension (3%) and hyperglycemia (3%) observed.Conclusions: Identifying bone health factors may still be relevant in selected early phase ADT-investigational agent trial patients, emphasizing the need for improved methods for capturing baseline bone health and studying ADT-investigational agent and concurrent medication interactions on bone health.https://www.frontiersin.org/article/10.3389/fonc.2020.01125/fullfracture riskADTprostate cancerbone mineral densitycomorbidities |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zin W. Myint Charles A. Kunos |
spellingShingle |
Zin W. Myint Charles A. Kunos Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013 Frontiers in Oncology fracture risk ADT prostate cancer bone mineral density comorbidities |
author_facet |
Zin W. Myint Charles A. Kunos |
author_sort |
Zin W. Myint |
title |
Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013 |
title_short |
Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013 |
title_full |
Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013 |
title_fullStr |
Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013 |
title_full_unstemmed |
Bone Fracture Incidence After Androgen Deprivation Therapy-Investigational Agents: Results From Cancer Therapy Evaluation Program-Sponsored Early Phase Clinical Trials 2006–2013 |
title_sort |
bone fracture incidence after androgen deprivation therapy-investigational agents: results from cancer therapy evaluation program-sponsored early phase clinical trials 2006–2013 |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2020-07-01 |
description |
Introduction: Androgen deprivation therapy (ADT) is a primary treatment option for patients diagnosed with locally advanced-stage or metastatic prostate cancer. Androgen deprivation can be achieved either by radical orchiectomy or by medical castration using a gonadotropin-releasing hormone agonist. ADT has been linked to an initial 12-month loss of bone mineral density, a risk factor for weight-bearing bone fracture, and therefore, a confounding hazard for adverse event when patients are enrolled on early phase trials. To better understand the frequency of ADT-investigational agent-related bone fracture, we conducted a retrospective study of National Cancer Institute Cancer Therapy Evaluation Program (CTEP)-sponsored early phase trials to determine the number of fractures observed among enrolled prostate cancer patients.Patients and Methods: 464 locally advanced-stage or metastatic prostate cancer patients were identified among seven ADT-investigational agent trials conducted between 2006 and 2013. Demographic, co-morbidity, treatment, and adverse event variables were abstracted from CTEP databases and descriptive statistics were used.Results: 464 men had a median age of 64 years, were mostly white (90%), and had a performance status of 0 or 1 (98%). The number of new bone fractures occurring on or after ADT-investigational agent treatment was very low (4.6 per 1000 person-years). The median pretrial prostate specific antigen level was 29 ng/mL and most men (71%) had prostate cancer histopathology Gleason 7 score or higher. In these trials, 43 percent of men had bone only and 35 percent had bone and visceral metastatic disease. The most frequent grade 1 or 2 adverse events were fatigue (36%), hot flashes (27%), and anemia (17%). Grade 3 or higher adverse events were rare, with hypertension (3%) and hyperglycemia (3%) observed.Conclusions: Identifying bone health factors may still be relevant in selected early phase ADT-investigational agent trial patients, emphasizing the need for improved methods for capturing baseline bone health and studying ADT-investigational agent and concurrent medication interactions on bone health. |
topic |
fracture risk ADT prostate cancer bone mineral density comorbidities |
url |
https://www.frontiersin.org/article/10.3389/fonc.2020.01125/full |
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