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Archive for Alpharadin (radium-223)

The world wide supply of Xofigo (radium Ra-223 dichloride) available for patients will run out on October 10, 2014. Xofigo is the newly FDA approved treatment for men with castrate resistant metastatic prostate cancer (CRPC) with bone metastases without any known visceral metastases.

Individual batches of drugs are inspected prior to release to patients. Bayer’s regular inspection process found that two batches contained material unrelated to Xofigo.

The FDA posted a notice about a Xofigo shortage on October 7, 2014. Malecare obtained more information from Ms. Gissoo Decotis, Deputy Director of Oncology Advocacy Relations and Joseph Germino, MD, PhD, Vice President of United States Medical Affairs for Bayer HealthCare, LLC.

Dr. Germino assured Malecare that all doses of Xofigo that have been released to either their commercial patients or to men in clinical trials, have passed all inspections and are completely safe. Dr. Germino said, “patients should not be worried or concerned about the quality of the material that has been shipped or administered. “

Bayer is in the process of informing all physicians who do administer Xofigo about the production halt, said Ms. Decotis. If you are a man currently taking Xofigo or are interested in starting Xofigo, contact your doctor today.

In a way, this is good news. The drug inspection and safety process seems to work. Bayer not only seems to have acted quickly, but is keeping Malecare informed so that we can keep you informed. The bad news is that as of today, no one at Bayer knows what caused this contamination, according to Ms. Decotis. Some men might not receive Xofigo on schedule and others will need to delay their treatment. Indeed, some…if not, many, men…might not live long enough to see the supply replenished.

The length of time it will take for Bayer to resolve the problem and then to restart production will be of concern to men who have partially completed the protocol. Xofigo is delivered as an injection into a vein once a month (every 28 days) over a six month period for a total of six injections. Ms. Decotis reports that the total shelf life of radium-223, the main component of Xofigo, is approximately four weeks and its half-life is approximately 11 days.

Paragraph removed. Please click here to see October 10 posting explaining why.

According to Ms. Dicotis, Bayer’s statement is, “At this time, Bayer is unable to anticipate when distribution of Xofigo can be resumed.”

Xofigo is manufactured by only one plant, in Norway.

BOTTOM LINE

1- Bayer has assured us that any drug received by anyone to date is safe and meets all quality standards.
2- How long this production shut down will last is unknown.
3- Men in the middle of receiving Xofigo should contact their physicians to discuss what, if any, alternative treatments might be appropriate at the present time.

Malecare will continue to monitor the situation and make sure that all of our readers are kept fully informed as we learn more about this situation.

Joel T. Nowak, M.A., M.S.W. and
Wendy A. Lebowitz, Ph.D., M.P.H.

Somehow I have been negligent and not let people know that I have written and posted a major update of my “Guide to Advanced Prostate Cancer.” As in the past, it is available as a free download from the Malecare web site. Helping me to update the book was prostate cancer survivor Craig Pynn and my own caretaker, Wendy Lebowitz.

Anyone reading the first edition will be surprised when you see how many changes and updates this edition has included. It now has a very extensive conversation about living in the world as a cancer survivor as well as more information on how to deal with your doctors. There is additional information about the newest drugs and treatments available to those of us living with advanced prostate cancer.

This book is different from anything else you have read about prostate cancer. It is written squarely from the survivor perspective with multiple tips and out of the box ideas about coping with prostate cancer and its treatments. Prostate cancer survivors suggest many of the ideas and “fixes” as they share how they have dealt with the disease and the treatment side effects.

This book is not doctor oriented or doctor written. It is accurate and honest. It deals with the real issues we as prostate cancer survivors face on a daily basis.

Due to the support of Malecare it is offered without any charge. To download the book go to the Malecare web site (www.malecare.org) and then click on the tab marked Advanced Prostate Cancer. There you can sign up by providing your email address to receive the link to download the book.

The first edition was downloaded over 50,000 times. I received many very positive reviews, but I believe this updated edition is much better.

Joel T Nowak, M.A., M.S.W.

Officials from the National Institute for Health and Care Excellence (Nice) have made a preliminary decision not to recommend covering the drug radium-223 dichloride (Xofigo) for use for men with prostate cancer that has spread to the bone.

This latest draft guidance from Nice states that Bayer has not provided information on how Xofigo performs in contrast to other currently available drugs for use in the health service in England and Wales.

Malecare is urging that Bayer provide the required information prior to NICE making their final determination so that men in need will not be denied this safe and effective drug.  We know that Xofigo can extend survival by 3.6 months and improve the quality of life with only minor side effects.

Men qualifying for Xofigo are already have very progressed disease with multiple bone metastases.  It is nothing short of criminal that they be denied this proven treatment, especially when they are in a position where there are so little alternatives and often suffering with significant pain.

According to Nice chief executive Sir Andrew Dillon: “Clinical specialists told the committee that radium-223 (Xofigo) would be used as an alternative treatment option to docetaxel as an initial treatment, and abiraterone as a second-line treatment when the disease has progressed. However, Bayer did not to provide the committee with any data on how well radium-223 works compared to docetaxel or abiraterone or, only comparing it to a placebo.”  I find this confusing, as Xofigo should not be used as an alternative to docetaxel or abiraterone, but as an additional treatment.

Joel T Nowak, M.A., M.S.W.

Most people don’t know of the great work that has been carried out by group of determined advocates on behalf of men with advanced prostate cancer. These hard working advocates, who reach out across different advocacy groups (Malecare, PCRI , PHEN, PAACT and USTOO) have formed a committee they call the The Early/Expanded Access Committee (EAP).

The EAP meet with pharmaceutical companies on a regular basis to encourage them to make their promising drugs and treatments available to individuals before they have formally received FDA approval. They do this by the way of a vehicle they call the Early Access Program (EAP). The EAP identify drugs that are designed to treat men with advanced prostate cancer, that during their phase III trials clearly demonstrate great safety profiles and excellent efficacy, but have not yet received formal FDA approval.

As mentioned, the EAP meet with pharmaceutical company representatives to open the door for drug access, they help identify doctors who are willing to use these drugs, under the FDA guidance as a EAP clinical trial so that men don’t need to wait around for formal FDA approval. Not only does this program offer early access, it provides the pharmaceutical company and the FDA with a wealth of additional material about the safety and efficacy of the treatment which can be factored into their ultimate decision about approval.

THE EAP provides new hope for families around the world, they provide a paradigm that will be used in prostate and all other cancers in a short period of time.

The EAP has had three major successes to date, abiraterone, enzalutiamide and radium 223. Each of these drugs was made available to men in need prior to their receiving approval from the FDA, with the blessing of the FDA. The EAP recently performed an analysis of their impact with each of these drugs.

Jan Manarite (PCRI) who is an active member of the EAP, for the EAP “After the Expanded Access Committee had some success promoting and encouraging Expanded Access with our 3rd drug (radium 223), I always wanted to get the numbers, just to see what we did. Here’s what it looks like. I continue to think that small groups with simple goals can do big things….”

————————————————————————————————————————————

EAP Numbers – Patients Served

abiraterone *-    432 men received the treatment under the EAP from 33 states and the District of Columbia from Oct 2010 – Apr 2011

enzalutamide ** 508 men received the treatment under the EAP from  25 states and 6 Canadian Provinces from May 2012 – Aug 2012

radium 223***   200 men received the treatment under the EAP from 18 states from Jan 2012 – May 2013

TOTAL MEN SERVED –     1140

Sources:

* Joanne M. Vanak, RN, MSN, Senior Director, Scientific Advocacy, Janssen – 1/16/14

** Nahla Hasabou, MD, CCRP, Medical Monitor, Oncology Medical Science, Astellas – 9/3/13

*** Svetlana Babajanyan MS MD, Medical Director, Bayer HealthCare Pharmaceuticals Inc. – 8/5/13

This program is a roaring success fostered by the hard work from a number of different prostate cancer advocacy organizations as well as a number of dedicated physicians and researchers.  One also needs to acknowledge the supportive role that the FDA has decided to take in encouraging these Early Access Trials.

Joel T. Nowak, M.A., M.S.W.

Men with metastatic castration-resistant prostate cancer (mCRPC) in Québec, Canada now have access to Zytiga (abiraterone acetate) prior to having chemotherapy.

Effective February 3, 2014, the province has added ZYTIGA to the public drug formulary for the treatment of mCRPC in men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy (ADT).

In July 2011, ZYTIGA was approved by Health Canada for the treatment of men with mCRPC who had received prior chemotherapy containing docetaxel after failure of ADT. Health Canada approved a second indication for ZYTIGA in May 2013 for the treatment of men with mCRPC who are asymptomatic or mildly symptomatic after failure of ADT.

Québec joins British Columbia as the second province to add ZYTIGA to its public formulary for men with mCRPC who are asymptomatic or mildly symptomatic after failure of ADT.

On the European front men with metastatic prostate cancer can now get radium-223 as it has now been approved by NHS England.

In April 2013 NHS took responsibility for cancer drugs and on February 2014,following a review of data by the chemotherapy clinical reference group, radium-233 (Xofigo) was added to their approved list.

In a statement, health secretary Jeremy Hunt said: “Better access to effective medicine is a priority for the Government, and we are delighted that these new drugs will mean more patients will join over 38,000 cancer sufferers who have already benefited from the fund.”

Prostate cancer drugs become increasingly available for men all over the world, but not at a rate that still sees many more men than necessary continue to suffer and die when there are proven drugs and treatments languish waiting for redundant reviews.

Perhaps our remarkable politicians and government administrators could go back to the thinking well and fix the system. Perhaps they should consider an interim automatic approvals for a drug once they have been approved somewhere else by one of their large and respected counterparts in the world. They could still perform their own review and come to their own conclusion, but while we wait these vital treatments will be available to their own citizens. This is a simple and safe approval system that should not threaten each county’s independence and speed the delivery of drugs to those in significant need.

Joel T. Nowak, M.A.S., M.A.

Now that Radium-223 Dichloride (Xofigo) has been approved by the FDA for use in men with castrate resistant prostate cancer with bone metastases we will begin to see the actual treatments happening. The next question in the process that will arise is whether or not it is safe and effective to re-treat an individual with additional rounds of the drug once it has failed.

In many of the other treatments we use for advanced prostate cancer we have found that it is possible to go back after a treatment failure and re-institute the treatment and see a positive result. Will this work with Xofigo and given that it is radiation is it safe to retreat a man?

To begin to answer these questions there will be a new phase 1-2 clinical trial to evaluate the potential of Xofigo retreatment. The trial whch is scheduled to begin in November (this month) still has not formerly begun.

It is expected to enroll 40 men who meet the following criteria:
1. The man has already received the full 6 treatments of Xofigo.
2. The man has finished the initial treatment cycle (6 injections) more than 30 days ago.
3. The man has no enlarged lymph nodes greater than 6 cm.
4. The man has no visceral metastases (lung, liver, soft tissue) greater than 1 cm.
5. The man has no brain metastases.
6. The man has not had any chemotherapy since the last Xofigo treatment cycle.

The trial will have as its primary outcomes (results):
• Evaluating the number of men with either treatment-related AEs (adverse events) or SAEs (serious adverse events) [ Time Frame: Up to 7 months ] [ Designated as safety issue: Yes ]
• NEvaluating the number of participants with Radium-223 dichloride-related SAEs in the active follow-up period [ Time Frame: Up to 2 years after last treatment ] [ Designated as safety issue: Yes ]
• Any changes in complete blood count [ Time Frame: Up to 2.5 years ] [ Designated as safety issue: Yes ]
• The total number of participants who discontinue Radium-223 dichloride treatment due to treatment emergent AEs or death [ Time Frame: Up to 7 months ] [ Designated as safety issue: Yes ]

To read more about the trial go to: Xofigo Re-treat Trial
ClinicalTrials.gov Identifier: NCT01934790

If you believe that you are qualified (having had Xofigo over 30 days prior) and would be interested in participating you should contact:
Dr. Oliver Sartor, Tulane University
Contact: Patrick Cotogno, pcotogno@tulane.edu, (504) 988-6542

Joel T. Nowak, M.A., M.S.W.

We are in the fortunate position because the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) continues to evolve as new agents with the ability to extend survival gain FDA approval. The most recently FDA approved treatment, the alpha emitting radiopharmaceutical radium-223 (Xofigo) was approved for men with bone metastatic prostate cancer.

Most other of the newly approved treatments was designed with the initial intention of providing an increase in overall survival (OS), but Xofigo is different.  Like the other already approved  radio emitting agents Strontium and Samarium which are beta-emitting agents Xofigo was initially explored solely as a palliative treatment option.  However, the investigation quickly changed once it was discovered in very early trials that Xofigo, not like the other  agents, also improved survival in addition to providing palliative benefit.

Besides a survival advantage, Xofigo also provides a great measure of superiority over the beta-emitting agents (which irradiate a large area including bone marrow) because as a alpha-emitting agent it only irradiates a very localized area.  Since the vast majority of prostate cancer bone metastasis are in the bone and not in the marrow, Xofigo is very affective in treating these mets while not damaging the bone marrow, a significant advantage over the beta emitting treatments.

Xofigo is a game changer with a huge potential for a major role in our treatment protocol.

Joel T. Nowak, M.A., M.S.W.

 

 

 

The first line of treatment for advanced prostate cancer is Androgen (male hormone) Deprivation Therapy or ADT. Once the PSA progresses (climbs) while still on ADT and with testosterone levels <20 ng/ml a man is said to be castrate resistant. At this juncture a man will need to continue on ADT while adding additional drugs to his therapy regimen.

The following is an alphabetical list of potential drugs that have been FDA approved (alphabetical because there is limited sequencing evidence available to determine the best order to take these treatments).

Jevtana® (cabazitaxel) used in combination with prednisone after the failure of docetaxel therapy (chemotherapy). Usually reserved to be used after Zytiga and Xtandi, but not required. Cabazitaxel is a semi-synthetic derivative of a natural taxoid, so it is related to docetaxel, but it still works after docetaxel failure.

Novantrone® (mitoxantrone) disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells. It is usually held as a drug of last resort for men with prostate cancer as it does not convey any additional survival but it can provide palliative benefits.

Provenge® (sipuleucel-T) is an autologous cellular (made of your own cells) immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. The treatment sensitizes the immune system to prostate cancer cells. It is best used in an early disease state with a low PSA.

Taxotere® (Docetaxel “chemotherapy”) is an anti-mitotic treatment that interferes with cell division, especially fast growing cells. It encourages apoptosis, or programmed cell death.

Xofigo® (Radium-223 chloride) is an alpha emitting radio (short range radiation) pharmaceutical that seeks out bone metastases. It is used in men with symptomatic bone metastases and no known visceral metastatic disease.

Xtandi® (Enzalutamide aka MDV3100) is an androgen receptor antagonist drug, or a drug that blocks the cancer cells from absorbing and using the androgens that are being manufactured in the body. Approved only in the post-chemotherapy disease state. Sometimes, it is referred to as a “super” Casodex because of its similar, but souped up action.

Zytiga® (abiraterone) plus prednisone is used to treat men who have mCRPC. It is approved for both pre-chemotherapy and post-chemotherapy (docetaxel failure) disease states. It works by blocking the production of androgens from three sources; testicular, adrenal, and prostatic tumor tissues.

All the list drugs have the possibility of having many different and significant side effects. Before starting any of these drugs talk to your oncologist and learn about which side effects are serious and should be reported to the doctor or for which you should proceed to an emergency room for assistance. When in doubt, act – call the doctor or go to the emergency room.

Joel T. Nowak, M.A., M.S.W.