Elisa on Pazopanib

[Olga]

There is some logistical problem here. To resect or ablate/radiosurgery mets she probably would need to stop Pazopanib for at least a week before and a week after the procedure due to a bleeding risk. If it is working, then when stopped the growth might go faster without the block and who knows how well it will react when the pazopanib restarted? Or may be if this is a soft tissue met the bleeding risk is low and she might be on the Pazopanib, I do not know.

[Bonni Hess]

Hi Olga,
If Pazopanib is similar to Cediranib regarding increased hemorrhage risk, which I think that it is, Elisa would most likely need to discontinue Pazopanib for one to two weeks pre and post-op as Brittany had to when she had her small abdominal met resected. However if a met is growing and not responding to the Pazopanib as was the case with Brittany's superficially located abdominal met, the benefit of resecting the met to reduce tumor load may outweigh the risk of discontinuing the TKI temporarily. Dr. Sawyer had wisely told us that the abdominal met needed to be removed because "it wasn't being a team player", and interestingly it wasn't until after the met was resected that she began to have significant tumor shrinkage and disappearance. Thankfully, Brittany did not experience any increased tumor growth or disease progression during the time that she was off of the Cediranib pre and post op, although that was certainly a concern for us in making the decision. Certainly if a met continues to grow and is getting so large that it poses a risk or is interfering with the effectiveness of the drug because of the increased tumor burden, I personally think that it needs to be resected/ablated/or treated with radiosurgery while the TKI is temporarily discontinued. Unfortunately, as with everything with this very challenging disease, there are no definitive answers and all we can do is try to be as well researched and informed as possible before making any treatment decision.
With special caring thoughts and continued Hope,
Bonni

[Bonni Hess]

Dear Philipp,
The following post and information from Ivan may be helpful in educating/convincing Elisa's oncologists about the critical importance of regular brain MRI's for ASPS patients and the need to schedule Elisa to have one much sooner than the now scheduled MRI in November:

Re: Ivan rocking it since 2003

by Ivan » Tue Jun 11, 2013 12:46 am

To anyone who wants to get a brain MRI, but their oncologist is too stupid to give it to them without symptoms, here is a list of published literature which supports the practice - http://www.cureasps.org/forum/viewtopic.php?f=8&t=796 Seriously, we've had multiple people die for this exact reason. The ignorance is mind-boggling!

With deepest caring, healing wishes for Elisa, and continued Hope,
Bonni

[Johannes]

Dear all,

There is not much to report on our side. Elisa is still taking Pazopanib, with the overall tolerable side effects. When she is already tired, or when it's hot, she does get quite bad headaches more often now. Her last CT scan of the chest showed stability / perhaps minimal growth (1 or 2mm) of a few mets. I guess this is balancing off the minimal shrinkage that was - perhaps - noted in the previous report. The next chest CT one is not yet scheduled, but we hope to have it in November. In late November she'll also have a brain MRI, Meanwhile, we are waiting for the results of a full body bone scan and an MRI of the thigh that were both done last week.

Bonny, I think I didn't elaborate on oncolytic viral therapy. This provides a good overview:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2883714/

We contacted a doctor in Ottawa who is part of a research team on these oncolytic viruses. He said that they had used their viruses in preclinical models of sarcoma with some success but that to date they had not been allowed to test them in sarcoma patients. We will check with him again in early 2014.

I hope you are all enjoying a nice weekend,
Johannes

[D.ap]

Johannes and Elisa

Thank you some much for the update
We are so sorry to hear of Elisa's side effects. We hope that tomorrow brings her joy

She has been on pazopanib for how long to date?
Do you have more frequent scans as a result of taking pazopanib? as in MRI's of the brain ?
Is the focus on the lungs or primary, primarily?
Here's to good news on the bone scan and MRI report

Our hearts and prayers are with you both and your families

Sincerely
Debbie and family

[Johannes]

Hi Debbie,

Thanks for your message.

Elisa has been taking Pazopanib since last January. She doesn't really have scans more often, especially when compared to the very frequent scans when she was part of the Cediranib trial at the NIH/NCI, and it's not always easy to have these scans scheduled...

Take care and best wishes,
Johannes

[Bonni Hess]

Dear Johannes,
I am sorry that I somehow missed your thoughtful update since I was traveling and away from the computer when you posted in October. I am so glad that Elisa's most recent chest CT showed relative stability and that her Pazopanib side effects are overall tolerable. The possible slight 1-2 mm. increased growth of a couple of her lung mets could certainly be attributable to the place that the CT sliced the mets, but I would encourage you to request that the scans be compared to her scans from when she first started the Pazopanib nine months ago in January rather than just the previous scan because scan to scan there may appear to only be minimal growth, but accumulated growth over a longer period of time can be more significant and concerning. I Hope that the results of Elisa's October full body bone scan and thigh MRI were good and that they showed no new tumors and shrinkage of her large primary tumor in her thigh. I will be anxiously awaiting your next update with those scan results, and sending most positive thoughts and very best wishes for good scan results from her late November brain MRI and her next chest CT.
Thank you for the thoughtful shared information and link regarding oncolytic viral therapy. I will be looking forward to more information about this promising new treatment when it becomes available.
Take care Johannes, give Elisa and yourself a special hug from me, and keep in touch with the Board as you are able.
With special caring thoughts, healing wishes for Elisa, and continued Hope,
Bonni

[Johannes]

Dear all,

Just a quick note that there are no major changes on our side. We are still waiting for a CT scan of the chest to be scheduled so there's no update in this regard. Frustrating. But Elisa had an MRI of the brain, the first one in two years, and everything is clean!

The side effects of Pazopanib haven't changed much either. Hair colour change, diarrhea, head aches, etc.

We tried to discuss a plan B with her oncologist last week, since it would be good to know what could be done if Pazopanib alone is not efficient any more. We talked about adding Sirolimus (or another mTOR inhibitor) to a lower dose of Pazopanib, but the reaction was very negative. According to her oncologist, there is simply not enough data available and that so far, all these combinations haven't shown good results and have only increased the toxicity levels. So for the moment we are just hoping that Pazopanib alone will continue to work and that we won't have to make another treatment decision soon!

With my best wishes to everyone,
Johannes

[Bonni Hess]

Dear Johannes,
Thank you for your thoughtful update and shared information. I am so very happy that Elisa's two year brain MRI was clear which is wonderful news I however don't understand why her oncologists aren't scheduling annual brain MRI's given the known risk of ASPS to metastasize to the brain and then quickly progress if it does. Hopefully you will be able to get a chest CT scheduled for Elisa soon so that you will know the status of her lung mets. She should also have an abdominal/pelvic CT or MRI at the same time as her chest CT if she has not had one recently as a chest CT alone is not adequate to determine possible disease progression to other areas of the body. Has she had any recent scans of her large primary tumor in her thigh, and if so, has it shown any shrinkage from the Pazopanib treatment?
I am glad that she is continuing to be able to tolerate the side effects of the Pazopanib. I Hope that you will both be able to enjoy a most happy holiday season and that the coming new year will bring the miracle of healing and renewed good health for dear Elisa, and abundant joy for both of you.
With special caring thoughts, happy holiday best wishes, and continued Hope,
Bonni

[Bonni Hess]

Hello again Johannes and Happy Healthy 2014 to you and Elisa :-)
I Hope that this finds you and Elisa having enjoyed a wonderful holiday season and a happy beginning to the New Year. I Hope too that Elisa is continuing to have a successful response to the Pazopanib and tolerating the side effects of the drug. Hopefully you were able to get her chest/abdominal/pelvic status CT scans scheduled and they showed/will show continued disease stability and tumor shrinkage/disappearance. You haven't mentioned anything in your most recent posts about the suspected spinal met that you had posted about last summer, and I am wondering what the status of that lesion is? I will be anxiously awaiting your next update and as always, am holding dear Elisa and you very close in my heart and my most caring thoughts.
With warm hugs, deepest caring, healing wishes for Elisa, and continued Hope,
Bonni

[Bonni Hess]

Dear Johannes,
In case you didn't see Olga's important post in the Medical Publications topic, I am posting it here for you as it seems to re-enforce/validate the critical importance of resecting the primary tumor to increase the effectivness of systemic treatments by reducing tumor burden. I Hope that this information is helpful to you in making treatment decisions for Elisa relevant to her still present primary thigh tumor.
with special caring thoughts, healing wishes for Elisa, and continued Hope,
Bonni

Unresected primary tumor reduces efficacy of treatments

by Olga » Mon Jan 20, 2014 10:26 am

We discussed before that the presence of the primary tumor could be involved in less efficient antitumor activity of antiangiogenic agents. We were mainly talking about the TKI drugs that many of our patients are on with the limited/transient efficacy, and if the unresected primary tumor presence might reduce the efficacy of the TKI drugs (we have some ASPS patients with the unresected primary tumors when it was found at the already metastasized stage, we generally always advocate the primary resection as possible although our suggestions are based on the mostly anecdotal data when people with the primaries resected fare better). This subject is discussed all over diseases spectrum and is addressed in the new article publ. in Ann Surg Oncol. 2014 Jan 14.
Bevacizumab Efficacy in Metastatic Colorectal Cancer is Dependent on Primary Tumor Resection."
http://www.ncbi.nlm.nih.gov/pubmed/24419756
The authors performed a retrospective analysis of factors associated with overall survival (OS) in a study cohort of 409 mCRC patients and it was found, that addition of bevacizumab to chemotherapy is associated with improvement of OS ONLY in patients with primary tumor resection.
If you find yourself in a situation when the oncologist is not supportive to an idea of resection of the primary tumor, this article might be used as one of the blocks of the logical ground for the primary tumor resection justification before you start any systemic treatment.

[Johannes]

Hi,

I wanted to let you know that everything is alright for Elisa overall, although there have been a few developments. The last CT scan of the lungs that was done in early January (the first since the summer...) showed that the biggest met in the lungs had grown several mm, measuring then 3cm. Since all the other mets had remained stable, the oncologist suggested to treat this met with stereotactic radiosurgery and to continue with Pazopanib. We are lucky to have a cyberknife in Montreal, and since the whole procedure is really not invasive at all, without significant side effects, we decided to give it a try. The treatment was given in five fractions over two weeks. Elisa felt some unusual fatigue and also some pain in the chest, but luckily this only lasted for a few days. We only have to keep in mind that any pneumonia over the next months would be a side effect of the radiosurgery and would have to be treated differently (not with antibiotics).

For anyone on a TKI and thinking about this: at one hospital they told us that Elisa should stop taking Pazopanib a week before and resume a week after. At the other hospital where she finally got the treatment, they advised her to continue as long as possible since there are hints that the radiosurgery actually works better in combination with such a drug. In the end, Elisa only stopped the day before, took it over the weekend in between the treatments and resumed a few days after the treatment.

We won't know right away whether the treatment actually worked; we were told that we would have to wait at least six to eight weeks before seeing anything and that the nodule might appear (or not!) as big as before on the next CT scan, and might only disappear later.

Regarding the side effects of Pazopanib, and similar to Mario's experience, Elisa has less diarrhea, and her hair colour seems to be coming back (after over 12 months of treatment).

Bonni, I agree (once again!) with you that removing the primary is probably a good idea. We are still hoping to buy some time until another drug (if it's not Pazopanib!) to reduce the size of the tumour so that the surgery would not be as invasive. At this time, we are really reluctant to compromise on Elisa's pretty good shape and quality of life. But we are aware that keeping the primary in the body is risky...

Best wishes,
Johannes

[Bonni Hess]

Dear Johannes,
It is so good to hear from you and I am so grateful that overall Elisa is continuing to do relatively well with stable lung mets except for just one lung met which had increased in size. I am grateful too that the met was able to be treated with a non invasive Cyberknife treatment, and am very Hopeful that the procedure was successful in shrinking and ultimately destroying the met. As we found with Brittany's superficial abdominal met experience four and a half years ago, it seems that for some reason all of the mets don't always respond to the TKI drug, and as Dr. Sawyer said, "they aren't being team players" and need to be removed or destroyed with resection, radiosurgery, or ablation. Thank you for the interesting shared information on the two different schools of thought regarding discontinuation of a TKI prior to treatment. Of course the "hints that the radiosurgery actually works better in combination with such a drug" may be the case with a non invasive procedure like Cyberknife, but because of the known risk of hemorrhage with TKI drugs, it is probably still necessary to discontinue a TKI drug for at least one week pre and post surgery to prevent dangerous hemorrhaging.
You mentioned that Elisa's January chest CT was the first one that she has had since last summer which is perplexing and concerning to me since it seems that she should be scanned every three months as part of the protocol with a newly approved drug. Also, she should be receiving abdominal/pelvic CT's along with the chest CT's, and at least an annual brain MRI and bone scan since stable disease in one area of the body unfortunately does not guarantee disease stability in another area. It is critically important to be vigilant and thorough with scanning to have an accurate assessment of the status of the disease and the effectiveness of the drug.
I will be anxiously awaiting your next update and holding very tight to Hope for good news from the results of Elisa's lung met Cyberknife treatment, as well as a continued successful and sustained response to the Pazopanib. In the meantime, take care Johannes, give yourself and Elisa warm hugs from me, and know that my most caring thoughts and very best wishes are with both of you.
With deepest gratitude for your thoughtful sharing, and with special caring, healing wishes for Elisa, and continued Hope,
Bonni

[D.ap]

Hi,

I wanted to let you know that everything is alright for Elisa overall, although there have been a few developments. The last CT scan of the lungs that was done in early January (the first since the summer...) showed that the biggest met in the lungs had grown several mm, measuring then 3cm. Since all the other mets had remained stable, the oncologist suggested to treat this met with stereotactic radiosurgery and to continue with Pazopanib. We are lucky to have a cyberknife in Montreal, and since the whole procedure is really not invasive at all, without significant side effects, we decided to give it a try. The treatment was given in five fractions over two weeks. Elisa felt some unusual fatigue and also some pain in the chest, but luckily this only lasted for a few days. We only have to keep in mind that any pneumonia over the next months would be a side effect of the radiosurgery and would have to be treated differently (not with antibiotics).

For anyone on a TKI and thinking about this: at one hospital they told us that Elisa should stop taking Pazopanib a week before and resume a week after. At the other hospital where she finally got the treatment, they advised her to continue as long as possible since there are hints that the radiosurgery actually works better in combination with such a drug. In the end, Elisa only stopped the day before, took it over the weekend in between the treatments and resumed a few days after the treatment.

We won't know right away whether the treatment actually worked; we were told that we would have to wait at least six to eight weeks before seeing anything and that the nodule might appear (or not!) as big as before on the next CT scan, and might only disappear later.

Regarding the side effects of Pazopanib, and similar to Mario's experience, Elisa has less diarrhea, and her hair colour seems to be coming back (after over 12 months of treatment).

Bonni, I agree (once again!) with you that removing the primary is probably a good idea. We are still hoping to buy some time until another drug (if it's not Pazopanib!) to reduce the size of the tumour so that the surgery would not be as invasive. At this time, we are really reluctant to compromise on Elisa's pretty good shape and quality of life. But we are aware that keeping the primary in the body is risky...

Best wishes,
Johannes

Hello Johannes and Elisa

We hope that all is well and you are getting good reports on the lung procedure
I was curious why the lung if pneumonia were to of occurred would NOT be treated with antibiotics ?

Thanks in advance
Debbie

[Johannes]

Hi Debbie,

We didn't ask further questions about this; I believe the point is that it's not a "normal" pneumonia but as a side effect of radiotherapy, it would have to be treated differently (perhaps with steroids? I am sorry, I don't remember!). But apparently any radio-oncologist would know about this.

Hope this helps,
Philipp