Optimal treatment.....

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Currently the optimal treatment for hormone positive breast cancer is by an aromatase inhibitor and the relatively new drug, Palbociclib.  I have been prescribed Letrozole as an aromatase inhibitor.  This is a drug that's been used successfully for many years and its role is to stop the secretion of oestrogen.  Oestrogen is the hormone which feeds hormone positive breast cancer cells.  They are greedy little creatures, cancer cells, and will search out oestrogen and gobble it up.  Even postmenopausal women still produce a small amount of oestrogen and that's enough to keep those breast cancer cells growing and spreading so it's vital that all oestrogen is stripped completely from the system and that's how Letrozole has been very effective but, as I've mentioned several times, eventually those greedy cancer cells find a way of creeping in the back door and getting past Letrozole's defences and off they go again, munching their way and spreading again.

Until now, when that happened, the only way to beat the cancer cells at this game has been to change to a different form of ridding the body of oestrogen and buying patients a little more time.  Eventually, I believe, the cancer cells get wise to everything that's thrown at them in the form of inhibiting oestrogen production and chemotherapy is needed.  Chemotherapy is not actually the optimal treatment for hormone positive breast cancer, although until not many years ago, breast cancer was seen as one disease.  It's now known that there are several forms of breast cancer and hormone positive breast cancer is treated on its own merits, so to speak.  Tumours are biopsied and categorised and, once their type is known, treatment is decided upon.  Chemotherapy is the last in the list of defences because it kills all cells as well as the cancer cells, as most people know, and by the time a breast cancer patient has been treated to all the goodies in the oestrogen inhibiting cookie jar, they're fairly unwell, to say the least.  Chemo is harsh on the body; even harsher on a body that has been battling similar but slightly less harsh side effects for a number of years without respite.  

To make it clear exactly what a woman with hormone positive breast cancer has gone through by this time, it's necessary to explain the side effects of Letrozole and its pals.  We get hot flushes like you wouldn't believe; postmenopausal women will know what I mean by this but the hot flushes we get from menopause is nothing on those we get from oestrogen inhibitors!  Night sweats ditto.  Then there's hair loss - not all, for which I'm extremely grateful - but enough to make a difference.  Skin dries out and not only skin but all mucous membranes, i.e. eyes, nostrils, sinuses, mouth, throat, hair, the list goes on.  It also causes muscle and joint aches and pains and a few other annoying symptoms that we just have to accustom ourselves to because, my main point being we take this drug every single day for the rest of our lives, no time off, not ever, not one single day so we never get a break from these side effects.  If we're adaptable in nature, that's what we do - adapt to the fact that we will always feel uncomfortable.  If we're not.... umm...I'm not exactly sure how that feels because, fortunately for me I am adaptable.

Researchers worked tirelessly to find something to overcome this problem and they came up with the exciting new drug I've mentioned, Palbociclib or Ibrance.  I've discussed the effort it took Pfizer to convince the FDA that this was a useful, safe way to enhance hormone positive breast cancer treatment so I won't repeat it in this blog post because I want to move on.  Once it was approved in the US by the FDA many other countries also approved it and it became available as an accepted treatment, albeit  expensive.  This treatment is also taken for the rest of our lives.  Bear in mind that, because it's a lifetime treatment expense becomes over-riding issue.  I'm not 100% sure of the cost in other countries but I know that, eighteen months ago, it would have cost us $5,000 to $7,000 per month for us to buy overseas.  Add to that travel and accommodation expenses every three months, because it was only possible to obtain three months' worth in each prescription and you can see that we have to weigh up our options.

Australian authorities, in their infinite wisdom, decided that FDA approval was not sufficient for Australian women to be prescribed Palbociclib and its new cousin, Ribociclib, even though 52 other countries did,  so Pfizer was forced to hold a trial especially for approval of the TGA (Therapeutic Goods Authority) and, also as I've mentioned earlier, I was fortunate enough to be accepted on that trial which is ongoing.  Every day I'm grateful for the fact that I obtained a place and every day I feel both sad and angry for the women who were unable to gain a place and therefore access to this wonderful new drug therapy.  The PBAC (Pharmaceutical Benefits Advisory Council) has studied the drug and decided, wrongly, that the side effects are too harsh and the benefits not great enough when compared with Letrozole only treatment therefore hundreds, perhaps thousands, of women have not been granted the extra months or years that Palbociclib can grant them while we all wait for the next drug to come into being at the hands of researchers.  Palbociclib eventually did become available in Australia in May, 2017 but only at the price I've mentioned if it's purchased overseas which is, I believe, about $5,000 per month for life.  

Our greatest wish is for hormone positive breast cancer, of which 70% of all breast cancer patients are comprised, to eventually become a chronic illness rather than a disease which eventually, inevitably becomes terminal in a time frame of which we have no idea.  In other words, we can accept being chronically ill; we can accept fairly horrible side effects;  we can accept the life limiting effects of cancer and its treatment if, in return, we can live without the constant shadow of progression of disease which hangs over us and which is always in the back of our minds no matter how courageous we are or how good we are at kidding ourselves and others that this isn't the case and we're not at all concerned.


The trial:   For those who are interested in how the trial works for me, this trial does not use placebos for half of the cohort and Palbociclib for the other half.  It's already been proven that Palbociclib is so effective that it is more than unfair, it's  dangerous for women on a Palbo trial to be given placebo instead of treatment, which is why I'm so angry that, until now, the PBAC has refused to subsidise this important breakthrough.

Palbociclib is given in cycles because its side effects cause havoc with the body's blood cells (once again a disclaimer - I'm not a medical person so I'm explaining it in my own words as I understand it).  We're given 21 days of treatment with the drug and then we have a break to allow the bone marrow to recover.  This is necessary because our immune systems are severely compromised by the treatment and most of us suffer from Neutropenia, some to a greater degree than others.

To quote Wikipedia,  "Neutropenia or neutropaenia is an abnormally low concentration of neutrophils (a type of white blood cell) in the blood.^[4] Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood.^[5] Patients with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening (neutropenic sepsis).^[6]

After the 21 days of taking a Palbociclib tablet every day we take one week's break and then have a blood test to check our neutrophil count.  If our level has recovered sufficiently we're then started on a new cycle.  If our level has not recovered, we have a second week's break and then have another blood test.  This is how it works for me because I tend towards moderate to severe neutropenia.  I have a two week break, another blood test and then I'm given a new 21 day supply of Palbo tablets.

Palbociclib does have side effects similar to chemotherapy but, as I've mentioned, they are not as harsh on the body, nor as sudden but, because the break we have at the end of the 21 days of tablet taking is only just enough for the immune system to recover to a level far lower (in my case) than normal, the effects are going to be with us for the rest of our life.  If we decide we can't cope with the side effects, we have to weigh up the option of taking the risk of inevitable treatment failure and the strong possibility that Palbociclib will give us a much longer life span.  What would you do?  I know what I'm going to do.  Buy every minute of time that I can!

The side effects are similar to those of Letrozole but add to that extreme fatigue as the cycle progresses, due to the lowering of our blood count; a bit more hair loss; mouth ulcers and sore gums the same as caused by chemotherapy, cold sores, nausea (sometimes leading to vomiting) and decreased appetite - at least these are the side effects I experience.  Not all women experience all side effects and some women say they hardly feel affected at all.  I've found I can't face the kind of food I used to eat and I've had to experiment (sometimes with disastrous results!) until I've found a diet that suits me and I stick rigidly to that.  I've been given a prescription for an anti-nausea tablet which helps.

I'm extremely grateful to be on the trial because it means I'm monitored closely, in return for which I keep a daily diary for the company which manufactures the drug for them to use to convince the TGA that this drug is safe, efficacious and quite easily tolerated.  In the diary, I note the day and the time of day I took both Letrozole and Palbo (the trial is for women on both drugs who haven't been treated with any other treatments prior to these two) and any side effects I've noticed.

Three to six monthly I'm treated to a CT scan and a bone scan.  The bone scan is because my metastases are in my bones.  So far my scans have remained stable.  Stable is good; regression would be even better;  progression is bad.  I thank Palbociclib for this because, very soon after I commenced treatment with it, which was three months after I commenced on Letrozole, my clinical condition began to improve and I began to feel a whole lot better than previously.  Some of my pain decreased, although I can't say how much is due to Palbo effect and how much is due to the heavy duty painkiller meds I take and which I've now adjusted to.

I'm looking forward to the time that Palbociclib and Ribociclib become affordable to all women who need them ~