Elisa on Cediranib

[Johannes]

Hello,

It’s been a while that we haven’t updated the board on how Elisa is doing.

First, the short story: GOOD NEWS! She was enrolled in the Cediranib trial at the NIH/NCI about three months ago, and the first re-staging scans showed a reduction of 23% of the biggest lesions in the lungs!

To the details: We decided against the ARQ 197 trial, because Cediranib definitely seemed more promising at this stage. Moreover, additional staining of the tumor at the Memorial Sloan-Kettering revealed only “focal and faint” expression of the Met protein, according to the pathologist “significantly below what is being called 3+ or 2+ staining”. Although the markers used are apparently only investigational, these results were definitely not encouraging to try a c-met inhibitor.

Elisa was enrolled as one of the last patients, but they also told us that the trial might be enlarged via an additional requirement of tumor biopsies.

The first 6 weeks or so of the treatment were, to be honest, really tough. Elisa reacted almost immediately, i.e. after 24 hours, to the medication with severe pain at the site of her primary in the thigh. The thigh also swelled a lot. We could see a significant change. It was a nightmarish period, she could at times barely walk, it was difficult to control the pain with morphine, and the bi-weekly trips to Bethesda were very exhausting for her. But after 5 or 6 weeks the pain decreased and she started to feel much better. And all this seems ages ago and secondary after hearing these good news…

The primary tumor in the thigh (a previous MRI report indicated 20 x 12 x 7cm in diameter) seems more difficult to measure than the lung mets. Moreover, due to some communication error at the NIH, the thigh was at first not included in the CT scan. They quickly found out and ordered another scan of the femur. But since Elisa had already eaten, they did the scan without contrast, which makes a comparison even more difficult. Anyway, the tumor has shrunk a lot (definitely more than by 23%!), and the PET scan showed that the SUV has also diminished (from 13.6 to 6.2). Regarding the mets in the lung, we thought that the radiology report of the CT scan was pretty short. But it does mention that the largest nodule in the left lobe currently measures about 1.5cm in diameter. If that’s true, then this seems like a very significant shrinkage, since previous reports always mentioned the biggest lesion (also in the left lobe) to be around 2.9cm in diameter. Of course the detailed measurement doesn’t matter that much, since Elisa will continue taking Cediranib anyway. We will see at the time of the next re-staging if she (hopefully) continues to respond.

Regarding side effects, she now gets diarrhea and stomach cramps more often, but it’s manageable and she doesn’t seem to lose weight. Her skin is still a lot more sensitive than usual. Besides that, everything (blood pressure etc.) seems OK at the moment. She only had to start taking thyroid hormones because her TSH went up a lot. What has been annoying lately is that she’s losing a lot of hair. We know that this is not the worst thing to happen but still we hope this won’t continue… Has anyone else experienced a hair loss?

That’s it for now, but we’ll post any further results.

Take care,
Johannes

[DottyW]

Johannes,
It's great to hear that Elisa is seeing significant shrinkage of her tumors. It seems to be a rough go at first. From Jordanne's experience, I would suggest trying to avoid dairy for the diarrhea. Jordanne has seen a pretty strong correlation between them so we suspect that the cediranib is making her lactose intollerant. She wasn't previously.
with prayers and caring thoughts,
Dotty

[Bonni Hess]

Dear Johannes,
Thank you for your very thoughtful and informative update on Elisa's Cediranib experience thus far, and for sharing the WONDERFUL news about her VERY good and encouraging first re-staging scan results. I'm so sorry that she experienced such a difficult and painful first six weeks on the Cediranib, but am very grateful that she is now feeling much better and able to tolerate the side effects of the medication. Brittany, who has now been on her Cediranib treatment for 15 months, did not experience the intial significant hair loss which you say that Elisa is having, but she has noticed that she has been losing a little more hair than normal in her hairbrush during the past couple of months. Hopefully the other ASPS patients who are on the Cediranib Trial will write to update more about their Cediranib expereince thus far and their most recent scan results, and to share information regarding the hair loss issue and other side effects that they are experiencing. This updated shared information is so vitally important to all of us in the ASPS Community.
I will be holding Elisa and you very close in my heart and special thoughts, and holding very tight to Hope for continued stabilization of her disease and increased shrinkage of her primary tumor and lung mets. Please give Elisa gentle hugs and best wishes from me, and keep in touch with this Board as you are able.
With special caring thoughts, healing wishes for Elisa, and continued Hope,
Bonni

[Olga]

Johannes, you are saying that Elisa had to start taking thyroid hormones because her TSH went up a lot, but there are some articles that this drop in the TSH is the part of the mode of action of the tyrosine kinase inhibitors - it is how they work to block the growth and people with the biggst drops often get better response - tumor shrinkage. They actually are not sure if getting TSH back to norm would not interfere with the drug treatment ability. I am not at all advising not to take the hormones but I would try to keep it as min as possible and ask them about it - what do they think if it can alter the efficacy of the drug.

[DottyW]

Olga,
Do you have a link for any of those articles? I would be very interested in reading more as Jordanne's next visit to NIH is on Tuesday and they think they may put her on thyroid meds at that time. It would be great to have more information ahead of time.
Thank you in advance,
Dotty

[Johannes]

Hi everyone,

Thank you for all these cheering messages you've posted! This support is wonderful.

It's quite possible that the cramps and diarrhea I've experienced lately were linked to dairy products. Although I still have diarrhea a few times a week, I've been feeling much better when I avoid dairy products (including lactose free milk that I was taking even before starting Cediranib).

As for hair loss, I've been told that it might be linked to a lower thyroid function. It might be a coincidence: it seems to be getting under control at the same time as my TSH level.

Olga, this possible link between thyroid hormones and the efficiency of Cediranib is startling... I'm only taking a light dose (0.05mg per day), but I'll definitively look into it further and will talk about it on my next NIH visit. I'd also appreciate if you could post the link for these articles. Merci!

Take care,
Elisa

[Bonni Hess]

Dear Elisa,
It was good to hear from you and to hear that you are feeling better and that your hair loss is getting under control. It seems that the hair loss certainly could be related to low thyroid levels since that can affect so many things in your body.
At Brittany's appointment with Dr. Sawyer on Friday we discussed the issue which Olga raised regarding the possible impact of thyroid supplements on the efficacy of Cediranib treatment. Dr. Sawyer said that he is aware of this theory and that although Cediranib does affect the thyroid, he does not feel that the thyroid supplements significantly, if at all, affect the effectiveness of the Cediranib. He feels that the quality of Life problems which would result from not taking supplements to normalize low hormone levels are a greater issue than the unproven risk of possible lower treatment response. Brittany has been taking low dose thyroid supplements for Cediranib caused hypothyroidism since early in her treatment, and thankfully it does not seem to have affected the effectiveness of her treatment thus far. I too would be interested to read the articles which Olga cited regarding this issue if she is able to post them, and I will be interested in the results of yours and Dotty's discussions with the NIH doctors regarding their perspectives on this. In the meantime, please take care Elisa, know that my best wishes for a very successful treatment response are with you, and keep this Board updated with information regarding your Cediranib experience, side effects, and scan results as you are able.
With special caring thoughts and continued Hope,
Bonni

[Olga]

Hi Everyone, I am in Russia now with somehow limited access to Internet but I was trying to find that article that I read at some point - couldn't find it now. May be it was discussed in context of some specific drug of that class with the hypotesys that it might be the common mode of action of that class of drugs (TKI). Dr.Sawyer is definitely correct in his point that the treatment is a balance so I would follow the advice of the oncologist but try to stay at the lower possible dose of this hormone (and any other hormone supplement too). Ask around too, may be they have more information at NCI. Brittany experience seems to contradict this thoery so may be it was just a wild guess at some point that did not work out? May be it was in the ASCO annual meetings proceedings, not on the pubmed - they do not overlap, do a search there. I'll try to find it when I am back after Aug.15.