despite the widespread use of bone - targeted agents in the care of patients with bone metastases from prostate and breast cancer , questions regarding the optimal ; choice of agent , dose , dosing frequency , and duration of therapy remain unanswered , , , , , .
our research group is interested in designing and performing pragmatic de - escalation trials in both breast and prostate cancer patients .
however , before undertaking this research , it is important to survey potential patients regarding this type of study with respect to their understanding of their disease and use of their bone - targeted therapies ( i.e. denosumab , zoledronate , pamidronate or clodronate ) . the information obtained will facilitate appropriate pragmatic trial designs , which will positively impact patients potential willingness to participate .
this report summarizes the conduct and findings of a survey designed to collect information from canadian patients with breast or prostate cancer regarding their views of their current treatment regimen .
in addition , their opinions regarding the possibility of less frequent treatment administrations and participation in potential research studies to assess the effectiveness of this treatment option were also sought .
while we are aware of similar patient surveys around the use of bone - targeted agents for osteoporosis   and multiple myeloma , we are not aware of published work in patients with metastatic bone disease from solid tumors .
the survey was designed to collect specific information about the use of current bone - targeted therapy and patients perception of the goals of this treatment and alternative treatment schedules .
second , the survey gathered information regarding their perspectives on the concept of de - escalated bisphosphonate therapy , designed to help the study team develop an understanding of how patients would value a change in their therapy .
our survey was conceived and developed using an iterative approach by the research team with backgrounds in oncology and epidemiology , including expertise in survey design .
patients attending outpatient clinics at two canadian cancer centres ( the ottawa hospital cancer centre in ottawa and the sunnybrook odette cancer centre in toronto , canada ) who were receiving or had recently been receiving bone - targeted therapy for bone metastases from either prostate or breast cancer were approached .
the survey was available in both paper and online formats ( implemented via www.fluidsurveys.com ) , whichever the patient preferred to use , and took about 10  min to complete .
the survey was open to patients seen between august 1st and october 31st , 2012 .
local institutional research ethics board ( reb ) approval for the study was granted at both participating hospitals .
however , given the reb requirement that no personal patient identifiers could be collected , we were unable to collect information on the number of patients who took the survey away from clinic but then chose not to complete it .
as a result , a response rate can not be calculated . the survey consisted of close - ended multiple - choice and hybrid questions ( i.e. choose - one - and specify ) which were analyzed using a descriptive summary of findings in the form of frequencies and percentages using microsoft
excel 2010 ( microsoft corporation , seattle , washington ) and sas software ( version 9.2 , sas , cary , north carolina ) .
this data was used to qualitatively judge the respondents views of their current treatments and to determine their willingness to be treated with de - escalated bone - targeted therapy to allow the study team to clarify the value and feasibility of a future trial around this clinical question .
analyses were performed to present the overall response profile , as well as responses within the breast cancer and prostate cancer subgroups .
the survey was designed to collect specific information about the use of current bone - targeted therapy and patients perception of the goals of this treatment and alternative treatment schedules .
second , the survey gathered information regarding their perspectives on the concept of de - escalated bisphosphonate therapy , designed to help the study team develop an understanding of how patients would value a change in their therapy .
our survey was conceived and developed using an iterative approach by the research team with backgrounds in oncology and epidemiology , including expertise in survey design .
patients attending outpatient clinics at two canadian cancer centres ( the ottawa hospital cancer centre in ottawa and the sunnybrook odette cancer centre in toronto , canada ) who were receiving or had recently been receiving bone - targeted therapy for bone metastases from either prostate or breast cancer were approached .
the survey was available in both paper and online formats ( implemented via www.fluidsurveys.com ) , whichever the patient preferred to use , and took about 10  min to complete .
the survey was open to patients seen between august 1st and october 31st , 2012 .
local institutional research ethics board ( reb ) approval for the study was granted at both participating hospitals .
however , given the reb requirement that no personal patient identifiers could be collected , we were unable to collect information on the number of patients who took the survey away from clinic but then chose not to complete it . as a result , a response rate can not be calculated .
the survey consisted of close - ended multiple - choice and hybrid questions ( i.e. choose - one - and specify ) which were analyzed using a descriptive summary of findings in the form of frequencies and percentages using microsoft excel 2010 ( microsoft corporation , seattle , washington ) and sas software ( version 9.2 , sas , cary , north carolina ) .
this data was used to qualitatively judge the respondents views of their current treatments and to determine their willingness to be treated with de - escalated bone - targeted therapy to allow the study team to clarify the value and feasibility of a future trial around this clinical question .
analyses were performed to present the overall response profile , as well as responses within the breast cancer and prostate cancer subgroups .
a total of 141 patients responded , and included totals of 65 ( 46.1% ) and 76 ( 53.9% ) patients diagnosed with breast cancer and prostate cancer , respectively ( table 1 ) .
a total of 100% of breast cancer patients and 94.7% of prostate cancer patients were aware that they had received treatment with a bone - targeted agent at some point .
respondents had received bone - targeted agents for : <3 months ( 17.0% ) , between 3 and 12 months ( 37.6% ) , between 12 and 24 months ( 22.0% ) , and > 24 months ( 19.1% ) ; 4.3% of patients did not respond .
patients varied in the amount of time for which they expected to remain on therapy : 44.7% did not know for how long , 43.2% indicated as long as their doctor keeps prescribing it , 5.0% believed it to be as long as they remain well enough to attend their centre to receive it , and 6.4% did not respond .
these response patterns were similar for breast cancer and prostate cancer patients with a few small differences noted ( table 1 ) . among prostate cancer patients ,
the most commonly administered agent was denosumab ( 63.1% , as well as an additional 5.3% who in the past had received denosumab ) , followed by zoledronic acid ( 19.7% ) ( fig .
overall 44.7% of patients received their treatment at the hospital chemotherapy unit , while 27% received treatment via injections administered at home by a nurse or another individual ( fig .
a total of 31 patients ( 40.8% of all prostate cancer patients , or 45.6% of those responding to the related question ) reported being aware of potential side effects of their treatment . according to patients descriptions ,
the potential side effects of bone targeted agents were ; diarrhoea , constipation , vomiting , fatigue , flu - like symptoms , osteonecrosis of the jaw , hypocalcaemia , bone pain and water retention . within the breast cancer cohort ,
the most commonly used agent was pamidronate ( 87.7% ) , followed by zoledronic acid ( 9.2% ; fig .
1 ) . overall , 93.8% of patients reported receiving their treatments in the chemotherapy unit at their hospital ( fig .
2 ) . overall , 34 patients ( 52.3% ) were receiving their treatment every 3 months ( fig .
3 ) . a total of 28 patients ( 43.1% ) reported awareness of potential side effects , similar to those described by prostate cancer patients .
the most commonly reported reasons were : to reduce the chance of bone fractures due to cancer ( 78.0% ) , to slow the growth of cancer ( 53.2% ) , to reduce the chance of spinal damage ( 49.0% ) , to prolong survival ( 46.8% ) , and to reduce the chance of cancer pain ( 46.1% ) ( fig .
fewer patients indicated that it was related to prevent the need for radiotherapy / surgery to bones ( 29.8% ) or to the management of hypercalcaemia ( 24.1% ) .
the majority of respondents with prostate cancer ( 78.9% overall , or 93.5% of those that responded to the related question ) and breast cancer ( 75.4% overall , or 87.3% of those that responded to the related question ) would be willing to take a reduced dose of their medication if it were associated with the same clinical benefits as their current dose .
similarly , the majority of respondents with prostate ( 67.1% overall , or 79.7% of those responding to the related question ) and breast cancer ( 69.2% overall , or 88% of those responding to the related question ) indicated they would be happy taking the medication less often ( i.e. leaving the dose unchanged but receiving it less frequently ) if the clinical benefits were unchanged . eighteen and a half percent and 30.3% of breast and prostate cancer respondents , respectively , indicated a lack of interest in changing from their current 34 week regimen . if reducing the dose would lead to fewer side effects , 64.6% of prostate cancer and 46.1% of breast cancer patients indicated an interest in taking a reduced medication schedule and dose .
when asked if they would prefer a daily oral medicine or an injection in the hospital every 13 months , 21.1% of prostate cancer patients and 23.5% of breast cancer patients indicated a preference for taking oral medication daily , while 57.9% and 49.2% preferred an injection every 13 months .
overall , 39.2% of prostate cancer patients and 35.4% of breast cancer patients indicated a willingness to administer their own medication via an injection . when asked if they would be willing to enter a trial randomising between monthly and 3 monthly therapy , 64.6% of prostate patients and 58.2% of breast cancer patients indicated a willingness to participate in such a study .
a total of 141 patients responded , and included totals of 65 ( 46.1% ) and 76 ( 53.9% ) patients diagnosed with breast cancer and prostate cancer , respectively ( table 1 ) .
a total of 100% of breast cancer patients and 94.7% of prostate cancer patients were aware that they had received treatment with a bone - targeted agent at some point .
respondents had received bone - targeted agents for : <3 months ( 17.0% ) , between 3 and 12 months ( 37.6% ) , between 12 and 24 months ( 22.0% ) , and > 24 months ( 19.1% ) ; 4.3% of patients did not respond .
patients varied in the amount of time for which they expected to remain on therapy : 44.7% did not know for how long , 43.2% indicated as long as their doctor keeps prescribing it , 5.0% believed it to be as long as they remain well enough to attend their centre to receive it , and 6.4% did not respond .
these response patterns were similar for breast cancer and prostate cancer patients with a few small differences noted ( table 1 ) .
among prostate cancer patients , the most commonly administered agent was denosumab ( 63.1% , as well as an additional 5.3% who in the past had received denosumab ) , followed by zoledronic acid ( 19.7% ) ( fig .
overall 44.7% of patients received their treatment at the hospital chemotherapy unit , while 27% received treatment via injections administered at home by a nurse or another individual ( fig .
a total of 31 patients ( 40.8% of all prostate cancer patients , or 45.6% of those responding to the related question ) reported being aware of potential side effects of their treatment . according to patients descriptions ,
the potential side effects of bone targeted agents were ; diarrhoea , constipation , vomiting , fatigue , flu - like symptoms , osteonecrosis of the jaw , hypocalcaemia , bone pain and water retention . within the breast cancer cohort ,
the most commonly used agent was pamidronate ( 87.7% ) , followed by zoledronic acid ( 9.2% ; fig .
1 ) . overall , 93.8% of patients reported receiving their treatments in the chemotherapy unit at their hospital ( fig .
2 ) . overall , 34 patients ( 52.3% ) were receiving their treatment every 3 months ( fig .
3 ) . a total of 28 patients ( 43.1% ) reported awareness of potential side effects , similar to those described by prostate cancer patients .
the most commonly reported reasons were : to reduce the chance of bone fractures due to cancer ( 78.0% ) , to slow the growth of cancer ( 53.2% ) , to reduce the chance of spinal damage ( 49.0% ) , to prolong survival ( 46.8% ) , and to reduce the chance of cancer pain ( 46.1% ) ( fig .
fewer patients indicated that it was related to prevent the need for radiotherapy / surgery to bones ( 29.8% ) or to the management of hypercalcaemia ( 24.1% ) .
the majority of respondents with prostate cancer ( 78.9% overall , or 93.5% of those that responded to the related question ) and breast cancer ( 75.4% overall , or 87.3% of those that responded to the related question ) would be willing to take a reduced dose of their medication if it were associated with the same clinical benefits as their current dose .
similarly , the majority of respondents with prostate ( 67.1% overall , or 79.7% of those responding to the related question ) and breast cancer ( 69.2% overall , or 88% of those responding to the related question ) indicated they would be happy taking the medication less often ( i.e. leaving the dose unchanged but receiving it less frequently ) if the clinical benefits were unchanged . eighteen and a half percent and 30.3% of breast and prostate cancer respondents , respectively , indicated a lack of interest in changing from their current 34 week regimen .
if reducing the dose would lead to fewer side effects , 64.6% of prostate cancer and 46.1% of breast cancer patients indicated an interest in taking a reduced medication schedule and dose . when asked if they would prefer a daily oral medicine or an injection in the hospital every 13 months , 21.1% of prostate cancer patients and 23.5% of breast cancer patients indicated a preference for taking oral medication daily , while 57.9% and 49.2% preferred an injection every 13 months .
overall , 39.2% of prostate cancer patients and 35.4% of breast cancer patients indicated a willingness to administer their own medication via an injection . when asked
if they would be willing to enter a trial randomising between monthly and 3 monthly therapy , 64.6% of prostate patients and 58.2% of breast cancer patients indicated a willingness to participate in such a study .
despite the widespread use of bone - targeted agents in the care of patients with bone metastases from prostate and breast cancer , a number of important and practical clinical questions remain around optimising their use . in order to design and perform pragmatic clinical trials in these populations ,
it is important to obtain patient treatment information , perceptions and opinions that will help guide trial design to ensure sufficient participation .
this is of particular interest for studies evaluating treatment de - escalation where it is critical to ascertain patient 's willingness to participate . to our knowledge , we are the first team to implement use of this type of survey in these patient populations , although a number of de - escalation studies are either reported , , ,   or are ongoing .
our survey demonstrates that canadian breast cancer patients are more likely to receive pamidronate , whereas prostate cancer patients are more likely to receive either denosumab or zoledronic acid .
these differences reflect not only that the drugs proven to be efficacious in these populations are different ( i.e. only denosumab and zoledronic acid improve outcomes in prostate cancer ) , but also that the funding system for these agents in ontario differs .
any trial looking at de - escalated therapy will need to take these factors into account .
our findings also suggest that clinical trials evaluating single agents such as zoledronic acid or denosumab , ,   will not lead to broad changes in clinical practice in both disease sites .
in addition , for prostate cancer patients , such a trial will need to reflect the fact that a significant number of patients have switched from zoledronic acid to denosumab when funding for denosumab became available , thus future studies may have to allow for bisphosphonate use prior to denosumab treatment in the inclusion criteria .
patients in our survey population had been on bone - targeted agents for variable periods of time , again meaning that future trials will need to be reflective of this , and be flexible in the length of time a patient has been on a prior bone - targeted agent prior to study entry . to date , of the published trials , , only one   did not specify the maximum length a patient could have been on a prior agent .
interestingly , many patients perceived that the bone - targeted agent was slowing the growth of their cancer . given that these agents have shown no effect on either overall survival or progression - free survival in breast cancer , , , , . ,   or prostate cancer , , there may be a need to better inform patients of this fact .
preference for injectable therapy over oral therapy , contrary to our findings from a previous study , could reflect the fact that most patients have not received an oral bone - targeted agent for metastatic disease .
however , the practical advantages of an injectable therapy and the lack of need for extra - care ( taking the medication with water , not laying down shortly after po administration ) in an elderly patient population should not be ovelooked .
our sample was recruited from two cancer centres in ontario , canada and therefore reflects prescriptions practices in that province .
in addition , as the reb requirement was to allow no patient identifiers on the questionnaires , we could not tell how common it was for patients to refuse participation ( i.e. in place of a denominator for response rate , which we do not have ) . as a consequence , it is possible that our responding cohort consists of better informed , more motivated patients which may not be representative of all patients receiving treatment with bone targeted agents .
this too could be reflected by the large number of breast cancer patients who are already receiving 3-monthly bone - targeted therapy .
in an era of personalised medicine , involvement of patients in the design of future clinical trials is increasingly important . although our results suggest that patients still have misconceptions around the reasons for receiving bone - targeted agents , the similarities between prostate and breast cancer patients are interesting as both patient populations were aware of the main indications and toxicities of these agents .
however , given that patients receive a range of agents for varying periods of time and in different locations ( hospital vs. home ) means that the design of future trials will need to reflect this and be very pragmatic .
 backgroundin order to design studies assessing the optimal use of bone - targeted agents ( btas ) patient input is clearly desirable.methodspatients who were receiving a bta for metastatic prostate or breast cancer were surveyed at two canadian cancer centres 
 . statistical analysis of respondent data was performed to establish relevant proportions of patient responses.resultsresponses were received from 141 patients , 76 ( 53.9% ) with prostate cancer and 65 ( 46.1% ) with breast cancer . 
 duration of bta use was <3 months ( 15.9% ) to > 24 months ( 35.2% ) . 
 patients were uncertain how long they would remain on a bta . while most felt their bta 
 was given to reduce the chance of bone fractures ( 77% ) , 52% thought it would slow tumour growth . 
 prostate patients were more likely to receive denosumab and breast cancer patients , pamidronate . 
 there was more variability in the dosing interval for breast cancer patients . given a choice 
 , most patients ( 4957% ) would prefer injection therapy to oral therapy ( 2123% ) . 
 most patients ( 5864% ) were interested in enrolling in clinical trials of de - escalated therapy.conclusionwhile there were clear differences in the types of btas patients received , our survey showed similarity for both prostate and breast cancer patients with respect to their perceptions of the goals of therapy . 
 patients were interested in participating in trials of de - escalated therapy . 
 however , given that patients receive a range of agents for varying periods of time and in different locations ( e.g. hospital vs. home ) , the design of future trials will need to be pragmatic to reflect this . 
Introduction
Materials and methods
Survey development
Study population
Statistical analysis
Results
Respondent population characteristics
Current treatment
Patient's viewpoints regarding the indication for current bone-targeted treatment
Patients viewpoints regarding potential changes in therapy
Discussion
Conclusion
Conflict of interest statement
Supplementary materials