HELP! Brain mets-Gamma knife or traditional radiation?

No there are no clincial trials as yet on brain metastatis as yet, but there have been trials on others, so the safety profile of the drug is well known (incl one recent one copied below). Other features of the drug combine to support the theory that it can be used in brain metastatis (can cross the blood brain barrier and transport other chemo drugs there too) and even elsewhere in the body can be used in combination with chemo or radiation - mifepristone makes the cancer cells more sensitive to killing by chemo or radiation as well as having some activity against cancer itself.

 

Completing 3 clinical trials after a patent is lodged takes 10-12 years before an application to the drug regulators can be made to have the drug approved for x treatment (in the interime it's classed as "experimental".

 

Nonetheless, the drug has been available on a compassionate use program for some time for those cancer patients who have exhausted other options etc.  - that makes it a bit more difficult to obtain but not impossible.

However, the theory of it's potential effectiveness is based on the facts that:

1. mifepristone can cross the blood brain barrier (has been used effectively for meningiomas - benign brain tumours)

2. Studies demonstrate mifepristone works synergistically with chemo drugs and can negate multi-drug resistance in a wide variety of cancer cells

3. Studies show that it can enhance radiation treatments and make them more effective. 

4. It has activity against a range of cancers (laboratory trials) eg. ovarian, cervical, lung etc

5. A case report below is also published on metastatic colon cancer which demonstrates that in a human trial (hence case report)- albeit only two people at this stage), the drug alone had activity against cancer cells, is well tolerated and in addition it's safety profile is well demonstrated as it's been used in patients for several years in meningioma.

1992: Mifepristone (RU 486) treatment of meningiomas.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&

• “Mifepristone treatment resulted in control of tumor growth (stable disease) in 6 of 10 patients who had shown recent evidence of tumor growth. In 3 of these 6 patients, consistent tumor shrinkage was seen. author's modified,”

 2007: Synergistic effects of mifepristone on the cytotoxicity of cisplatin in cervical carcinoma cell lines and tumors grown in athymic mice

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17

 

·          “Our results suggest that mifepristone can improve the efficacy of cisplatin in cancer cells and this anti-hormonal drug therapy may be a candidate for further evaluation in combination with antineoplastic drugs in the treatment of cancer.”

 

Radiation Oncology Physicians:

http://www.mdanderson.org/departments/radiation/display.cfm? " target="_blank" rel="nofollow">http://www.mdanderson.org/departments/radiation/display.cfm?

·          “.... We have found that breast cancer cells pretreated with RU486, an anti-progesterone, have increased sensitivity to killing with irradiation.  The cellular mechanism and potential cross-talk with p53 and apoptotic pathways is currently being investigated.... “

 

http://www.mdanderson.org/departments/radiation/display.cfm? " target="_blank" rel="nofollow">http://www.mdanderson.org/departments/radiation/display.cfm?

·          “.... We have found that breast cancer cells pretreated with RU486, an anti-progesterone, have increased sensitivity to killing with irradiation.  The cellular mechanism and potential cross-talk with p53 and apoptotic pathways is currently being investigated.... “

 

2007: Evidence that progesterone receptor antagonists may help in the treatment of a variety of cancers by locally suppressing natural killer cell activity.

http://www.ncbi.nlm.nih.gov/pubmed/18225679?ordinalpos=18&am

 

2009 May;29

Mifepristone may halt progression of extensively metastatic human adenocarcinoma of the colon – case report

 

http://www.ncbi.nlm.nih.gov/pubmed/19443374?ordinalpos=1&

BACKGROUND: Mifepristone, a progesterone receptor antagonist has been found to improve the length and quality of life in various spontaneous murine cancer models including tumors without progesterone receptors theoretically by inhibiting an immunomodulatory protein that suppresses natural killer cell function in the tumor microenvironment. MATERIALS AND METHODS: Mifepristone 200 mg per day by mouth was given to two patients with stage 4 colon cancer with extensive metastases. RESULTS: Both patients not only survived far longer than expected but had marked improvement in their quality of life similar to mice. Though the metastatic lesions did not disappear, no new ones appeared for a long time and the ones present did not grow. The drug was extremely well tolerated. CONCLUSION: The use of progesterone receptor antagonists may present a novel immunotherapy to help fight cancer. A larger controlled study is needed.

Hello:

Thank you for the wonderful links, but I must be missing something. I could not find how any of this relates to renal cell carcinoma? It appears to me that most of these studies have been done on other cancers. (Not to mention, none on metastatic renal cell carcinoma brain lesions that I could find).  As you know, each cancer can be unique to the type of treatment that will be effective against it.  Unfortunately for us renal cell carcinoma suffereres, it is resistant to many chemo and radiation. Has an actual study with this agent (U-486) been done on renal cell carcinoma? Once again, excuse me if I missed anything.

Thank God for the age of targeted therapies and targeted radiation (Cybernife, Gamma, ect.)

I see your point, if you are out of options, and if you can get a doctor to prescrib this along with other chemo for compasionate use, what do you have to lose? It maybe difficult however, to get your insurance company to go along with it.

Thank you however, for bring this med up. It is good to know whats in development and I will keep my eye out on this one.

Krys

I just lost my friend to breast cancer.  She survived 17 years!  But last year she had full brain radiation due to multiple lesions also.  My husband has Stage IV RCC and we will not have full brain if his would go there.  We will have Gamma Knife.  She was never the same after the full brain.  Couldn't eat and didn't have quality of life.  I hate to write this or scare anyone but look up the side effects. 

 

On 6/2/2009 Bookmum wrote:

Hi Heritage Softail (we are also Harley riders),

Thanks for your response.  I just spoke to both Mayo and our radiologist here.  Rick is not a candidate for the Gamma Knife because he has too many lesions---which is a surprise because yesterday, the Oncologist told us there were only 3.  This is so frustrating.......trying to learn as much as we can is hard enough without getting contradicting info.  Deep breaths--we are meeting with the Radiologist again today so, hopefully, we can sort it all out.  Good luck.  My thoughts and prayers always include everyone on this board.   Sue (Bookmum)

 

Hope you got a 2nd opinion.  My husband had gamma knife last week for 6 mets and they said they have done it on as many as 11.

 

On 9/20/2009 gingery56 wrote:

 

On 6/2/2009 Bookmum wrote:

Hi Heritage Softail (we are also Harley riders),

Thanks for your response.  I just spoke to both Mayo and our radiologist here.  Rick is not a candidate for the Gamma Knife because he has too many lesions---which is a surprise because yesterday, the Oncologist told us there were only 3.  This is so frustrating.......trying to learn as much as we can is hard enough without getting contradicting info.  Deep breaths--we are meeting with the Radiologist again today so, hopefully, we can sort it all out.  Good luck.  My thoughts and prayers always include everyone on this board.   Sue (Bookmum)

 

Hope you got a 2nd opinion.  My husband had gamma knife last week for 6 mets and they said they have done it on as many as 11.

 

Where do you live?, and how old is your husband? That was a factor for us because at 71, I was really concerned about quality of life issues with whole brain radiation on my husband, but sometimes it may be the best course.

 

On 6/2/2009 Bookmum wrote:

Yesterday we found out that my husband has 3 small brain tumors (1 year ago had kidney removed -- mets to the lung and on Sutent since).  They said Sutent works well for the main body but not so effective for the brain.  The Dr here wants to start radiation right away.  I've been searching the computer and this Gamma Knife looks like an option--it's not offered here but we can get it 2 hours away.  Does anyone have any experience with this??

Thank you,  Bookmum

 

I hope this encourages you.  My son's father in law had a kidney removed 8 years ago, and the first sign of trouble was not his kidney, but a mass in his arm.  They removed the mass in his arm, put in a bone graft, then 2 weeks later removed the kidney.

One year later they radiated the arm.  He has had "spots" on his pancreas and liver for several years and they are checked every 6 months. They don't seem to grow and he does take rounds of Sutent for them.

He had cyberknife on his brain mets 2 years ago and initially seemed to be doing poorly (mostly being on the steroids due to swelling), but after 2 years, he wants to go out and hit some tennis balls.  Can't believe how well this guy has done for 8 years.

After studying the gamma vs. cyber knife, I would suggest gamma, and to be sure you feel very confident in your rad/doctor.  Ours was outstanding and Tim was tired and had little appetite for a few days, but is feeling better every day on that front.

Good luck in your decisions.