Abi Comes of Age

2012 has seen a series of regulatory approvals worldwide for Abiraterone Acetate, affectionately known as "Abi", and now marketed by Johnson & Johnson as "Zytiga".

In 2012 Abi was approved by all the main regulatory authorities throughout the world, having been approved by the FDA, EMA and TGA.

May saw the COU-302 phase 3 trial results announced at the ASCO conference in Chicago, which paved the way for the submission for FDA approval for use before chemotherapy.

On June 26th it was announced that the drug rationing watchdog NICE had approved Abi for use on the NHS for free prescription use in the UK.

On 10th December this year the FDA approved Abi for use in treating prostate cancer before chemotherapy.

Neoadjuvant Zytiga Eliminates Prostate Cancer

Zytiga can completely eliminate prostate cancer when given early enough as first line neoadjuvant therapy before surgery. A clinical trial has been conducted to evaluate the benefits of Abiraterone Acetate (Zytiga) when given early on, in the neoadjuvant setting before surgery. The results of this trial look very promising with results showing prostate cancer being eliminated in 10% of patients, and almost completely eliminated in 30% of patients, after 6 months of neoajuvant Zytiga.

Here are the testimonials of two prostate cancer patients who took part in the clinical trials of neoadjuvant Zytiga.

Patient #1

My PSA went up from 2.4 in 2004 to 3.9 in August, 2009 - that triggered a visit to specialist.

Biopsy done in November, 2009 - Gleason score of 8.

MRI in December, 2009 confirmed the cancer had spread outside the prostate.

February 12, 2010 I started the Abiraterone Trial.

Within one month my psa was down to 0.64.

By May 12, 2010 my psa was down to 0.02.

My surgery was on August 5, 2010.

On August 18, 2010 my doctor told me the results of the pathology report - 0.0% residual cancer.

From pathology report post-surgery - left pelvic lymph node negative; right pelvic lymph node negative; prostate - no residual prostatic adenocarcinoma

I lost 42 pounds
My cholesterol improved dramatically
My CRP level is now normal
I had surgery August 5th to remove the tumors
On August 18th my doctor informed me that there was 0.0% (none, nada) residual cancer

Bob

Patient #2

I was in the same trial and had similar results. A little history:

I was 59 when diagnosed. I had my annual check in July 2010. The DRE revealed a lump and my PSA was 19. The biopsy revealed Gleason grade 7 (4+3 and cancer in 7 of the 12 cores). An MRI also showed a suspicious lymph node in, as the doctor said, a strange place well away from the normal prostate drain field.

My treatment has entirely taken place at Seattle Cancer Care Alliance (Univ. of Washington Medical Center & Fred Hutchinson Cancer Research Center)under the care of Dr William Ellis (surgeon) and Dr James P. Dean (medical oncologist). I took part in a clinical trial of pre-adjuvant Abiraterone & Lupron plus Prednisone. This lasted 6 months. I then had an open radical prostatectomy on March 1, 2011. Surgery was required by the study, but it could be either robotic or open. I had open because of the suspicious lymph node. The surgeon wanted to do a very thorough surgical lymph node resection. The pathology report showed clear margins, no seminal vesicle invasion, no extracapsular invasion and no lymph node involvement. The suspicious lymph node showed that the clinical trial had an effect--there was evidence of inflammation which is present when a cancer has been destroyed. No active cancer was found. Because of the use of Abiraterone and Lupron, the pathologist cannot determine a post surgery Gleason score. The treatment effect makes that impossible. I have since had one PSA test with an undetectable result (>.03 at this lab. My next test is June 8th.

The side effects of both Abiraterone and Lupron are similar and were manageable for me. I had (and still have) hot flashes. Weight control was very difficult, although I only gained about 7 pounds. Libido drops to nothing as does potency. Fatigue was the primary problem, but it was manageable and I was able to work full time and continue with life as normal during the study. I had blood tests every two weeks.

Now that the treatment phase of this is over, I'm working with our daughter who is a registered dietician to make sure that I eat a very healthy diet. The weight is starting to come off and that should get easier as the testosterone continues to come back into my system. A good support system is vital. My wife is a breast cancer survivor so we knew the drill when this happened, but it is still a rough road.

I knew that I had an aggressive cancer so I wanted the most aggressive treatment. I didn't hesitate to take part in the trial as I wanted to bring every weapon possible in this fight.

John

How Fast Does Zytiga Work

Zytiga works very fast in its pharmacological action of lowering testosterone working within 30 minutes of being taken. Following oral administration Zytiga is absorbed by the small intestine into the bloodstream and starts working within 30 minutes and its effects last longer than 24 hours. It has a half life of 12 hours. So after 12 hours the plasma concentrations have reduced by half which is still an active concentration. So Zytiga is rapidly absorbed and starts inhibiting the enzyme CYP17 which blocks all androgen production within a few hours. The testosterone levels then gradually reduce down to zero over the next few days and have reached their lowest within a week. This brings about total androgen deprivation (TAD) which prevents androgen receptor positive prostate cancer cells from growing and the absence of androgens promotes tumour cell death by apoptosis.

The effects of total androgen deprivation is different in each case. Some men respond quickly to TAD whilst others do not respond at all and their PSA continues to rise. In some cases a sharp rise in PSA is seen initially following Zytiga treatment but then reduces after 2 months. In order to evaluate the efficacy of Zytiga it is best to look at the PSA trend over 3 monthly tests. This gives a clearer idea of the response since any initial increase should have subsided after the second reading and declined further after 3 months.

Zytiga to be Trialled as First Line Therapy

A three arm clinical trial has started looking at comparing Zytiga plus Prednisone alone, versus Zytiga plus Prednisone in combination with Degarelix, versus Degarelix alone for men who have received surgical prostate removal but the PSA has started to rise.

This will be the first time the Zytiga Prednisone Combo (ZPC) alone has been tested as the first line therapeutic option once surgery has failed.

Degarelix is a new LHRH antagonist given as a monthly injection and has similar activity in lowering testosterone levels to the LHRH agonists Lupron and Zoladex. Zytiga is taken as 4 x 250 mg tablets daily together with 5 mg of Prednisone daily. This is not a blinded trial since the patients will know if they are taking daily tablets or receiving a monthly injection.

Degarelix does not stop androgen production altogether and low levels of testosterone can be detected in the plasma of patients taking Degarelix. In contrast Zytiga inhibits CYP17 to bring about total androgen ablation as a single agent so Zytiga alone should work better than Degarelix alone and the combination of Degarelix with Zytiga will possibly be no better than Zytiga alone making since mechanistically speaking Zytiga makes Degarelix redundant.

Zytiga Increases Overall Survival When Used Earlier

The latest results from the COU-302 Phase 3 clinical trials of Abiraterone Acetate (Zytiga) show that Zytiga does indeed extend overall survival to a greater extent when used earlier in the treatment of this disease. This trial carried out on patients who had failed androgen deprivation therapy (ADT) but not requiring chemotherapy. The Zytiga Prednisone Combo (ZPC) arm had an overall survival of 35.3 months versus 30.1 months for the Prednisone plus Placebo arm. This equates to an extension of overall survival of 5.2 months which is the longest time for an agent tested in this category of patients. This compares to an OS extension of 4.6 months when used post chemotherapy. Maybe if Zytiga was used even earlier in the treatment of prostate cancer such as first-line neoadjuvant therapy the OS extension may be even greater.

Provenge Vs Sodium Bicarbonate

Which is the best treatment for prostate cancer Provenge or Sodium Bicarbonate. Well it turns out that according to patient testimonials easily available on the internet by searching on "provenge cancer testimonials" and "sodium bicarbonate cancer testimonials" that good 'ol baking powder (Sodium Bicarbonate ) comes out on top.

Xtandi Zytiga Jevtana Provenge Which is What ?

Anyone listening to the news has heard of new drugs for prostate cancer heralded as a golden era in drug development. First came Provenge the autologous immunotherapy vaccine that is supposed to lengthen overall survival (OS) by 4.2 months. Then came Jevtana, a new form of Taxol therapy active against Docetaxel resistant prostate cancer giving an OS benefit of 2.3 months. Then came Zytiga extending life by 4.6 months and finally the new kid on the block Xtandi with an OS of 4.8 months. But what are all these drugs and how do they really perform in clinical practise. Heres a summary of their attributes.

Provenge $93,000 per treatment consisting of 3 injections of a dendritic autologous witches brew concocted out of your own white blood cells delivered by a port which is inserted into the abdominal cavity.

Demostrated Benefits: None proven

Side Effects: Loss of money

Jevtana $24,000 for course of chemo injected by infusion over 1 hour.

Side Effects: Peripheral Neuropathy (Numbness), Hair Loss, Nausea, Liver Failure

Zytiga $60,000 per year for 4 tablets daily.

Side Effects: Hypokalaemia (Low Potassium) corrected by Prednisone

Xtandi $89,000 per year for 4 capsules daily

Side Effects: Seizure onset after 28 days.