Intermittent ADT

[Guest guest]

My previous send of this came out very oddly when I received it so I am re-sending HelloThis discussion group is dominated by the views of Chuck Maack. Chuck is, I am sure, very well intentioned and has devoted himself to researching the latest views on the treatment of prostate cancer. As a patient with asymptomatic advanced prostate cancer with no evidence of bone lesions, I find myself totally confused by the advice he offers. It is presented in a consistent manner with clearly no doubt in his own mind that the treatments he suggests offer the best hope of prolonging survival. I am fortunate in having access to private treatment at the best hospitals and by the leading cancer consultants in London. If I am to believe what Chuck says, all of these people, who have regular team discussions about their patients, and who attend conferences on prostate cancer all over the world, are blissfully ignorant of the best way to treat prostate cancer. In Britain we are very blessed in having a National Health Service which offers free treatment to all, even to overseas visitors and to immigrants with no history of social security payments. This contrasts with the (to me) scandalous situation in the USA where poor people and those without regular employment are routinely denied medical care. As many of you have discovered, prostate cancer treatments can be hugely expensive. My operations and radiotherapy have cost many tens of thousands of pounds but I have not paid a penny. Through my wife’s work, I also have access to private treatment but this simply means that I get a private room in a hospital a couple of miles from where I live, get treated a little sooner and at a time which suits me. The specialists are the same as they would be if I were treated through the NHS.Because of the potentially unlimited costs of healthcare, Britain has an organisation called the National Institute for Health and Clinical Excellence. This body advises the NHS on which treatments are worth pursuing and which ones offer little benefit. They update their guidance very regularly to take account of the latest drugs and treatment research. Here are some of their current recommendations about prostate cancer relevant to my own case: (you can find the full guidelines at http://www.nice.org.uk/cg58 ) (the underscoring is mine)1.5.5 Biochemical relapse (a rising PSA) alone should not necessarily prompt an immediate change in treatment.1.5.6 Biochemical relapse should trigger an estimate of PSA doubling time, based on a minimum of 3 measurements over at least a 6 month period.1.5.7 Men with biochemical relapse after radical prostatectomy, with no known metastases, should be offered radical radiotherapy to the prostatic bed.1.5.8 Men with biochemical relapse should be considered for entry to appropriate clinical trials.1.5.9 Hormonal therapy is not routinely recommended for men with prostate cancer who have a biochemical relapse unless they have:· symptomatic local disease progression, or· any proven metastases, or· a PSA doubling time of < 3 months.1.7.1 Healthcare professionals should offer bilateral orchidectomy to all men with metastatic prostate cancer as an alternative to continuous LHRHa therapy.1.7.2 Combined androgen blockade is not recommended as a first-line treatment for men with metastatic prostate cancer.1.7.3 For men with metastatic prostate cancer who are willing to accept the adverse impact on overall survival and gynaecomastia in the hope of retaining sexual function, anti-androgen monotherapy with bicalutamide (150 mg) should be offered.1.7.4 Healthcare professionals should begin androgen withdrawal and stop bicalutamide treatment in men with metastatic prostate cancer who are taking bicalutamide monotherapy and who do not maintain satisfactory sexual function.1.7.5 Intermittent androgen withdrawal may be offered to men with metastatic prostate cancer providing they are informed that there is no long-term evidence of its effectiveness. Recently I have been in the care of Dr Gibbs, Consultant Clinical Oncologist and Dr Shamash, Consultant Medical Oncologist at Barts Hospital in London. Barts is a leading centre of research into prostate cancer in the UK. I consider myself very fortunate in having access to such distinguished specialists. On their recommendation I am currently receiving Intermittent Androgen Deprivation Therapy using Triptorelin. My PSA responded very quickly to this reaching a nadir of 0.11 in six months. When I enquired whether we should not wait until it reached half of that (Chuck was suggesting 0.05 as a target) I was told that use of dutasteride routinely masks about 50% of the true level. As I have stated in other messages, the protocol suggested by Dr Shamash is that we suspend ADT until PSA reaches between 10 and 20 (we agreed on 15). After the extremely negative and derogatory comments from Chuck which caused me great anxiety I have tried to find other support for this protocol. Here is what I have discovered: 1. Two European studies (http://prostatecancerinfolink.net/2009/03/30/two-european-studies-suggest-value-of-intermittent-hormone-therapy) were published in early 2009. The first compared patients on continuous and intermittent ADT. Patients in the intermittent arm ceased treatment when PSA dropped below 4 ng/ml with a median time off-treatment of 52 weeks. There was little difference in survival rates between the two arms but side effects were more pronounced in the continuous arm. There were more cancer deaths in the intermittent arm but this was balanced by the increase in cardio-vascular deaths in the continuous arm. The second study also discontinued ADT when PSA was <4 and recommenced when PSA was >20 ng/ml or clinical symptoms appeared. Results showed that this was an acceptable treatment.2. There is a very good article about IHT on the Harvard Medical School website (http://www.harvardprostateknowledge.org/intermittent-hormone-therapy-for-prostate-cancer). This also mentions trials where therapy (combined androgen blockade) was stopped when PSA dropped below 4 ng/ml and restarted when PSA was between 10 ng/ml and 20 ng/ml. ‘On average, patients were able to stay off hormone therapy for about 10 months before starting treatment again. During that time, their testosterone levels returned to normal, and they reported an increased sense of well-being and recovery of libido and potency.’ I would certainly echo that.3. Article in Medscape News Today (www.medscape.com/viewarticle/442384_7) ‘A variety of reversible medical modalities have been used to induce testosterone suppression intermittently. Most of the reported phase II clinical trials have utilized approximately 8 months of androgen blockade followed by a period of no treatment when serial PSA is followed. Treatment is usually restarted after the PSA crosses a threshold of approximately 10 ng/mL. There are some anecdotal observations in the reported trials that the inability of a patient to reach normal levels of PSA with initiation of therapy could be considered a poor prognostic indicator. Significant findings consistent among all five studies were recovery of libido during time off treatment in men who had normal libido prior to initial antihormonal therapy, effectiveness of reinstitution of hormonal suppression in prior responders, and subjective improvement in overall sense of well-being during time between active hormonal suppression.4. In the conclusion of the same article: MAB (Maximal Androgen Blockage) does not appear to be significantly more effective than single-agent LHRH analog. Prescription of an antiandrogen during the first month of treatment with an LHRH analog should be considered, but prolonged MAB beyond 1 month is not superior to LHRH analog monotherapy. 5. On the website of The Prostate Cancer Charity:6. (www.prostate-cancer.org.uk/media/11668/hormonetherapy.pdf ) ‘In some cases your specialist may suggest a way of using hormone therapy called ‘maximal androgen blockade’, also known as ‘combined androgen blockade’. This uses both an LHRH agonist and an anti-androgen to treat the cancer. Some specialists think that maximal androgen blockade slightly improves survival in men whose cancer has spread to other parts of the body (advanced prostate cancer). Sometimes when an LHRH agonist on its own becomes less effective at controlling your prostate cancer, you may start to take an anti-androgen at the same time. However, because maximal androgen blockade can increase the risk of side effects it is not a commonly used as a first treatment for prostate cancer. I hope this is of interest. It has certainly reassured me that the course I am following is a sensible one. Bob Bob Bishop, MA, MBCS, CITPCrozier Data Consultancy62 Nevin DriveChingfordLondonE4 7LJ Phone: 020 8529 7816Mobile: 07962 206218Website: www.crozierchorale.com