Elderly patients have, to start with, both males and females, everyone thinks of females, an issue with bone health. Osteopenia and osteoporosis are prevalent. Some of our treatments will increase the risk of having osteopenia and osteoporosis and especially hormone manipulations that will reduce the testosterone level or the oestrogen level in these patients.
This may be one of the reasons why in some hormonally related tumours like prostate cancer and breast cancer there are bone metastases. We now have excellent evidence that the use of bisphosphonates in the setting of early treatment, adjuvant treatment, of breast cancer will reduce the mortality related to the cancer and this seems to be related to reduction in bone metastases. So these are very exciting data and have been the objective of a meta-analysis published by the EBCTCG under the guidance of Rob Coleman. In prostate cancer we do have evidence that we can reduce the impact of bone metastases and to some extent there has been a discussion that using bone protecting agents might reduce the incidence of bone metastases but this is still not a proven indication for these types of compounds.
Once the patient with any type of cancer has bone metastases we have excellent data to show that both denosumab and bisphosphonates have to be applied because they will reduce the risk of subsequent incidence of bone related events, as we say. Simply said, need for treatment because of the bone metastases giving to the patient signs and symptoms or the fact that unfortunately they might develop a fracture if we do not use these agents. There are lots of data today to say that we do not need to be as intensive in the treatment of the metastatic setting with monthly use of bisphosphonates but most experts say that the first few months you should use monthly bisphosphonate when you are speaking of intravenous bisphosphonates which are the best studied in that setting. Then we can go to an every three month treatment which is not yet proven with denosumab.
So the whole setting has been discussed by SIOG, the International Society of Geriatric Oncology, there is a guideline that has been published with the first author Jean-Jacques Body a couple of years ago which is still actual today and will be, however, revised as an ESMO guideline in the next few months. So I’ll be more than happy to come back to ecancer sometime next year with the new ESMO bone metastasis related guidelines.
Are there any modifications that can be made to improve quality of life?
Both denosumab and bisphosphonates are relatively well tolerated agents. In the first treatment some patients will have what we call an acute phase reaction which grossly we tell the patients you might have a flu for a couple of days. Usually this does not happen in the subsequent treatments and we explain this as being an immune reaction at the beginning which is then not repeated. The annoying point of the monthly treatment in the metastatic setting, as I said, for bisphosphonates is now a situation solved by the fact that we have good evidence that every three months after a few months of stabilisation of the situation is good enough. In the other setting we are not quite certain that we can delay the use of denosumab to every three months in the metastatic setting.
It is very important also to realise that in the adjuvant setting where there are no metastases the use of these agents every six months is recommended and, contrary to a widely-held belief that there is this terrible complication called osteonecrosis of the jaw with bone modifying agents, this does not happen in an every six month treatment. It does, unfortunately, happen when an intensive monthly treatment is given, therefore the recommendation is that all of these patients should have preventative oral hygiene measures in order to avoid subsequent dentist approaches that would need a tooth extraction that would then be complicated by this osteonecrosis.