Brittany on Cediranib trial Phase 1 in Edmonton

[Bonni Hess]

Dear Olga and Debbie, Thank you for your very kind and thoughtful responses. We really appreciate your valued insights Olga regarding the possibility that Brittany's long term TKI Cediranib use might be negatively affecting blood vessels or nerves and causing Brittany's concerning unexplained headache pain. This is something which we will defiinitely address and explore with Dr. Sawyer. Unfortunately we don't think there is much long term Cediranib side effect information and data available since Brittany is a pioneer in the long term sustained use of this relatively new drug.Thank you too for your alert observation that cortisones are hormones which is extremely important information for us to have in consideration of cortisone treatment for Brittany's suspected occipital nerve neuralgia since we have always had serious concerns about hormones possibly/potentially causing cancer progression based on our research and anecdotal patient observations. Regarding your question about Brittany's Cediranib dosage Debbie, she initially began the Trial in 2009 taking a daily dose of 45 mg., but the dose was reduced to 30 mg. per day after the first couple of months to help reduce the severe side effects and toxicity of the higher dosage. Brittany has continued on the 30 mg.daily dosage for the past six years. We will be in touch with both the radiation oncologist and Dr. Sawyer regarding Brittany's continued headaches and the possible occipital nerve neuralgia diagnosis and cortisone treatment recommendation and I will update this Forum when there is more information to share. Thank you both again for your deeply appreciated responses, special caring, and valued input. With deepest gratitude, special caring thoughts, much love, and continued Hope, Bonni

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Bonni

Found a headache related documentation to cediranib and headaches/seizures/high blood pressure?
Can take place after dosage of suntinib and other TKI's are taken.
Apparently very rare and many time misdiagnosed

Love
Debbie

Atypical reversible posterior leukoencephalopathy syndrome (RPLS) induced by cediranib in a patient with metastatic rectal cancer.

Kim CA1, Price-Hiller J, Chu QS, Tankel K, Hennig R, Sawyer MB, Spratlin JL.



Author information



Abstract

BACKGROUND:

Reversible posterior leukoenecphalopathy syndrome (RPLS) is a rare clinicoradiologic syndrome characterized by neurologic symptoms such as seizures, headaches, visual abnormalities, confusion and encephalopathy, accompanied by vasogenic edema of posterior white matter seen on neuroimaging. It has been reported in association with many anti-angiogenic therapies, including bevacizumab, sunitinib, sorafenib, pazopanib and regorafenib. Cediranib is a potent, orally available small molecule tyrosine kinase inhibitor with anti-angiogenic activity, which has been shown to have activity against various solid tumors.

CASE REPORT:

We present a case of a 65 year old male with metastatic adenocarcinoma of the rectum who received cediranib as part of a phase I clinical trial. He developed confusion and fluctuations in his level of consciousness. MRI of the brain revealed diffuse low level T2 signal abnormality in the cerebral peduncles, pons, and medulla and patchy T2 signal in both thalami, consistent with RPLS. With conservative management, including tight blood pressure control, his symptoms improved and MRI findings resolved.

CONCLUSION:

RPLS is a rare, but serious, clinicoradiologic syndrome which has been described as an adverse effect of many anti-angiogenic agents and should also be considered in patients on cediranib who present with neurologic symptoms along with vasogenic edema seen on MRI. If RPLS is suspected, cediranib should be discontinued and blood pressure should be aggressively controlled



http://www.ncbi.nlm.nih.gov/pubmed/24853074

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Hello Bonni and family

The headache/ pain center seems to be the best consult.
Need to pinpoint where the headache is coming from
Good night
Love
Debbie

[Bonni Hess]

Dear Debbie, I am so deeply grateful for your caring research and thoughtful shared information about the possibility of Cedranib related RPLS being a potential cause of Brittany's continued concerning headaches. We will share the RPLS report with both Dr. Sawyer and the radiation oncologist to obtain an opinion from them regarding this issue. While Brittany has some of the symptoms described in the report, her blood pressure has thankfully been consistently good and she has not experienced any seizures as described in the RPLS symptoms listed. If the doctors think that RPLS is a possibility we will request either a review of Brittany's September 9th brain MRI or a new MRI to try to evaluate if there is any vasogenic edema of the posterior white matter and/or diffuse low level T2 signal abnormality in the cerebral area. I will keep this Forum updated with the results of my communications with the doctors and their opinions regarding RPLS as a possible cause of Brittany's continued and increasing headaches. With deepest gratitude for your all of your extra effort and valued sharing, and with special caring thoughts, much love, and continued Hope, Bonni

[Bonni Hess]

Dear ASPS Community Friends, We were finally able to get Brittany an appointment with a headache pain specialist who administered a cortisone injection into the base of Brittany's neck targeting the occipital nerve. Very thankfully the injection has provided a couple of days of headache pain relief thus far. We understand that this is unfortunately probably not a permanent cure, but it can be repeated when necessary. In regard to my expressed concern about cortisone being a hormone which could possibly cause cancer progression, the doctor said that the small amount of cortisone should not pose any risk for that. Now on to Edmonton for Brittany's this week's 4 month Cediranib Clinical Trial chest, abdominal, and pelvic scans on Thursday which will Hopefully bring good news results of continued sustained six and a half years disease stability and no new tumors.
With much happiness for Brittany's headache pain relief, and continued Hope, Bonni

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Bonni
It's so good to hear of Brittany's head ache relief
Thanks for sharing the news and look forward to hearing update later in week.
Sharing in the joy
Much love
Debbie

[Bonni Hess]

Dear ASPS Community Friends,
It is with the greatest joy and relief that we received an early special Halloween treat with the VERY GOOD!! results of Brittany's Thursday's Clinical Trial chest, abdominal, and pelvic scans in Edmonton which showed continued stable disease and no new tumors . Brittany has now VERY thankfully had six and a half years of sustained disease stability since beginning the Clinical Trial in April 2009. She continues to be a pioneer in the long term use of this drug so the the long term side effects and risks are unknown. Dr. Sawyer was unable to be present for the scan results appointment as he was out of town for a meeting, but we met with his also very knowledgeable associate. We discussed with him our concerns about Cediranib related RPLS (Atypical reversible posterior leukoencephalopathy syndrome) being a possible cause of Brittany's concerning headaches, but he ruled RPLS out as he said it is extremely rare and Brittany does not have many of the symptoms usually associated with this condition. Also, Brittany's radiation oncologist's review of Brittany's September brain MRI did not detect any vasogenic edema of the posterior white matter and/or diffuse low level T2 signal abnormality in the cerebral area which is indicative of RPLS. Dr. Sawyer's associate confirmed to us the continued availability of Cediranib since Astra Zeneca is now thankfully planning to continue production of the drug because it is seeking pharmaceutical approval of Cediranib for ovarian cancer patients in Europe, so Hopefully Brittany is now no longer at risk of losing access to the drug which has provided her with dramatic shrinkage and disappearance of her innumerous and widely disseminated mets and six and half years of sustained disease stability, and all of us with so much Hope.
Take care everyone and keep in touch with the Board as you are able. We all need and can benefit from the invaluable help that shared researched and anecdotal treatment information can provide in helping us all to fight this shared battle with this very challenging disease.
With a very happy heart filled with great joy and relief and continued Hope,
Bonni

[Olga]

Awesome news, thank you. We are glad for Brittany and for other patients who might benefit from the cediranib in the future. It is a good news that Astra Zeneca is renewing its commitment to this drug, I am wondering if they are going to seek the approval for ASPS at all or we are to small of a group for them to bother. The trial at the NCI should be over soon too and they could be seeking its approval too.

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Bonni and family

Great news on scans and conversation on RPLS .
The Astra Zenecca news is a definite step on the right direction.
Thanks for including us in the great news!

I hope this day is still bringing Brittany a no headache experience.

Love
Debbie

[MartinBube]

Bonnie, excellent news. Brittany is the Hero that is opening the way for many others unfortunately ASPS patients that will need to go through this journey.

My prayers are with you and your family to continue this excellent results

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Bonni and family

Great news on scans and conversation on RPLS .
The Astra Zenecca news is a definite step on the right direction.
Thanks for including us in the great news!

I hope this day is still bringing Brittany a no headache experience.

Love
Debbie

Hi Bonni and Brittany and family
I am hoping that the headache is resolving itself and maybe it was a bug?
I've been reading an article on IV hydration , as I know Brittany has these performed routinely?


http://www.livestrong.com/article/25360 ... on/#page=2


Also I've read that cedirinib can cause left ventricle systolic issues but can be asymptomatic.
Does Brittany get echocardiograms performed with her physicals ?

Love
Debbie

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Tki in serotonin induced constriction of Basilar artery in vivo

http://stroke.ahajournals.org/content/29/2/494.full.pdf

[Bonni Hess]

Dear Debbie,
Thank you so much for your caring concern about Brittany's continued headaches, and for all of the helpful shared information. Unfortunately, Brittany is continuing to have headaches, but thankfully they don't seem to be as severe and debilitating as they had had been in August and September for a couple of weeks. We are continuing to try to determine a cause of the headaches and find an effective treatment for them through an oncology headache pain specialist, and Brittany is now on the 3-6 month waiting list for receiving somewhat experimental Ketamine infusions which will Hopefully help provide some relief/alleviate both the headache pain and severe long term chronic post-op spinal pain that Brittany heartbreakingly suffers. In regard to your question/concern about possible Cediranib caused left ventricle systolic issues, Brittany receives Echocardiogram monitoring as part of her regular Clinical Trial visits in Edmonton every four months, and thankfully the results have been normal thus far.
With deepest gratitude for your special caring and sharing, and with continued Hope,
Bonni

[Bonni Hess]

Dear ASPS Community Friends,
Christmas came early for our family with the priceless gift of Brittany's yesterday's preliminary VERY GOOD!! three month brain and spinal MRI results, which VERY thankfully showed no new tumors and continued disease stability in her brain and spine!! . With the scans having been done yesterday morning at the University of Washington, and the results appointment with the radiation oncologist a couple of hours later in the afternoon, we know and understand that these are only preliminary results which need to be finalized by the radiologist's formal scan report, but, as always, we personally reviewed the scans with the radiation oncologist and both the brain and spine looked clear with no visible new tumors and no sign of the multiple previously treated ones .
Interestingly, many of Brittany's very negative Cediranib side effects seem to be dissipating such as her severe mouth sensitivity and her complete intolerance of any kind or any amount of alcohol. She no longer needs to use children's toothpaste nor to avoid spicy hot foods which is in complete contrast to her previously being unable to even tolerate mild ketchup without it causing severe burning in her mouth. The subsiding of side effects has of course raised concerns with us that Brittany's body may have developed a tolerance and immunity to the Cediranib and that it may subsequently lose its effectiveness, but thankfully thus far her scans do not indicate that is the case. My husband Jim raised the theory to the radiation oncologist that perhaps there is a reduction in side effects because there is no more cancer for the drug to impact. Of course there is unfortunately no way to know if that might be the reason that Brittany's side effects are dissipating, but the radiation oncologist agreed that this could definitely be a possibility. That creates a dilemma in terms of Brittany continuing on the drug, but we are unwilling to gamble and take any chances at this time, so for now and until we are able to have some definitive proof that Brittany is macroscopically AND microscopically cancer free, she will continue to take the Cediranib as long as she is able to tolerate it, and it is available.
Heartbreakingly, Brittany is continuing to suffer from severe debilitating headaches which have been accompanied by vomiting which was of course very concerning to us since these are the symptoms that she experienced when she had brain mets, so we were especially worried about the brain scans, and immensely relieved that the scans were clear!! There are SO many possible causes of Brittany's headaches after all that her body has been through for the past 14 and a half years with brain tumor surgeries, Gamma Knife, spinal tumor surgeries, Cediranib, innumerous scans with contrast, high dose opiate pain meds, etc., so it is almost impossible to make a diagnosis to treat and resolve the headache pain. The radiation oncologist did say that post craniotomy ( brain surgery) headache pain is one of the most difficult things to treat and resolve, and that it can and does sometimes occur many years after the craniotomy which may be the case with Brittany. We are continuing to research and aggressively seek a viable pain relief treatment for her, and are holding VERY tight to Hope that the promising new Ketamine infusions for which she is now on a waiting list in Seattle to receive, will be able to provide both spinal and headache pain relief for her.
May this Holiday season and the rapidly approaching New Year 2016 bring all of you in our ASPS Community the precious gifts of healing, health, peace, and joy. Take care everyone and keep in touch with the Board as you are able.
With a heart filled with great happiness and relief, special caring thoughts for all of you, happiest Holiday best wishes, and continued Hope,
Bonni

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Bonni and family
From our family to yours. A huge hug and sigh of relief with the scans good results of no new lesions !

All our love
Debbie and family