Intermittent hormone therapy

[Guest guest]

The reason for my continued survival? Diagnosed in 1996 with 'non-trivial

disease'. In my case that meant advanced metastatic PC (T3N1M0) bPSA > 50, along

with lymph node and seminal vesicle involvement, and extracapsular spread that

required resection of part of the bowel. I was given 2-5 years.

I did a lot of homework in those days and I didn't take anyone's word for

anything. I got it all from the horse's mouth (i.e., original source - MedLine

Silver Platter in those days before PubMed). It was clear to anyone who read the

literature that there was a 'fly in the ointment' with the standard castration

therapy that limited patient survival with the onset of CRPC (castration

resistant prostate cancer). Intermittent therapy was 'experimental' and not

recommended for the majority.

Anyhow, times change. IHT is now 'official', according to the European

Association of Urology.

The references did not come through so I uploaded a PDF file. See also

http://fitcare.org.uk/ for full text.

Sammy.

Intermittent hormone therapy§

The great advantage of intermittent therapy over continuous castration therapy

is the biological respite from a host of unpleasant side effects. These include

loss of bone and muscle mass, decreased resistance to infection and allergy,

increased anemia and tiredness along with sleep and affect disorders. Castration

makes intermediate and advanced prostate disease a dog's life for many men, and

anything to lessen the impact is to be welcomed. A return to androgen means

recovering anabolic status and the gradual return to a normal male physiology –

something to be anticipated with delight in every patient's treatment calendar.

Some anecdotal reports include recovery of male erectile function during the

androgen phase of intermittent treatment – even after radical surgery has

damaged erectile nerves.

By 1980 an accumulation of reported IHT successes resulted in one of the first

publicationsi. A decade later a series of studies were commenced by

Bruchovskyii, at the Vancouver Clinic. Bruchovsky's investigation of the IHT

technique using synthetic LHRH analogs attempts to explain why repeated cycles

of castration worked as good as, and sometimes apparently better than, a single

chronic castration episodeiii. But despite reports which are the accumulated

wisdom of decadesiv,v IHT has been until very recently regarded as

experimental by many of the great and the good in the world of prostate cancer

sciencevi. Not limiting IHT to early stage disease, Oliver at St. Barts has

shown that withdrawal of castration therapy in patients even with metastatic

disease can improve their survival chancesvii.

Perhaps because intermittent therapy has not sat well with the androgen causes -

castration cures paradigm it has struggled to enter mainstream prostate cancer

thinking. A study published in 2007 heralds the change, reporting on collected

data from phase 2 studies of IHTviii, it presages EAU recommendations of the

same year. But after over sixty years of castration therapy embedded in the

collective medical consciousness, one wonders how much longer patients will have

to wait before more detailed recommendations can be made to determine who may be

selected for IHT.

" Thus, it is possible to offer intermittent androgen blockade to selected

patients, but results from randomized trials are still lacking. " ix

Is there a fear of the initial PSA spike produced when androgen recovery is

resumed? This characteristic rapid increase, probably due to up-regulation of

the androgen receptor, often slows down and may level out to produce a zero PSA

velocity. Some sources will insist on undetectable ultrasensitive PSA to be the

starting point for withdrawal of chemical castration. Others have put the PSA

starting point as high as 4.0 ng/ml.

Since prostate tumor is often well behaved, standard PSA kinetic algorithms can

be used to predict a ceiling PSA for cut-off purposes. Some suggest the PSA

ceiling during off treatment should be no higher than single figure numbers,

whereas other sources venture to go much higher. One rule of thumb for the PSA

ceiling has been 20 ng/ml or the value at time of diagnosis – whichever was the

less. However, PSA's in the region of 1000 ng/ml have been reported anecdotally

with intermittent treatment – because men need their testosterone, dislike being

castrated, and are prepared to take the risk.

Provided the situation is monitored sensibly with regular and reliable blood

testing, IHT facilitates a much improved quality of life at far less cost than

continuous chemical castration.