Cure Alveolar Soft Part Sarcoma International (iCureASPS)

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

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

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

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.

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

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

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

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.

Hi,

Happy New Year to everyone!

It's been a while that Elisa and I haven't posted an update. The situation hasn't changed much though: Elisa is still in the Cediranib trial at the NIH/NCI that she started eight months ago and continues with the initial dose of 30mg per day. After the very good response over the first few months (around 30% reduction of the lung mets and probably even more of the primary in the thigh), everything has been stable.

She still has the usual side effects: low thyroid function and high blood pressure, which are both under control with Synthroid and Losartan; diarrhea, which she gets pretty regularly, but since it isn't bothering her too much she doesn't take anything against it; and very sensitive skin, especially under her feet, and acne. In December, the severe pain in the thigh and chest that she had had when she started taking Cediranib came back for a few days.

Besides that, she is doing sports, such as biking, hiking and snowshoeing (we are in Quebec!), and she went back to university in September to do another master. Although she goes through ups and downs, overall she's doing great.

We will eventually want to look more deeply into alternatives, since Cediranib is unlikely to be a long-term solution. Switching to Sutent sooner or later might be option. We have also followed the discussion on the board on Crizotinib, a drug which seems really promising. But so far there is no plan B, and I guess Elisa will continue going to Bethesda for a few more months if the tumors remain (at least) stable.

Moreover, we hope to be able to think about having the primary resected, without removing a whole muscle or sort of cut away half of the thigh... The tumor has definitely become a lot smaller and fragmented thanks to Cediranib, but it's still a diffuse mass that seems very difficult to measure. From what we understood, the CT scans done at the NIH are not as precise as an MRI. We have an MRI scheduled at home in March and will then ask the surgeon and sarcoma specialist in Montreal, Dr. Turcotte, for his opinion. We'll keep you posted.

All my best wishes for 2011!

Johannes

Dear Johannes,
A most happy and healthy New Year to you and Elisa, and special thanks for your thoughtful update. It was so good to hear from you and to hear that Elisa is still on the Cediranib Trial after eight months with continued stable disease and tolerable side effects. Elisa's experience of dramatic tumor shrinkage during the first few months, followed by little to no additional shrinkage, but still having disease stability with no new tumors seems to be very typical of most of the other ASPS patients who have taken Cediranib. Brittany is an exception to this pattern since although she has had disease stability for the past almost 21 months since starting Cediranib, she initially had very little tumor shrinkage during the first few months, but then thankfully she began to have significant shrinkage and disappearance of the targeted lung and pancreatic mets, and as of her last scan in November, her targeted mets were no longer visible. I think that it is wise for Elisa to remain on the Cediranib treatment as long as she is having stable disease which is a major victory with this insidious disease. I also think that it is very important to explore scheduling resection of her now smaller and fragmented primary tumor as soon as possible if the surgery can be done with the understanding that she can resume the Cediranib Clinical Trial once the surgery is complete and she has sufficiently recovered. ASPS patient Jordanne who is also participating in the NIH Trial was able to temporarily discontinue taking the Cediranib twice for two different surgeries, and Brittany was allowed to do it during her Clinical Trial in Edmonton to have a superficial abdominal met resected. Removal of Elisa's very large primary tumor would certainly lessen her body's tumor burden and Hopefully allow the Cediranib to be more effective in shrinking her remaining mets. I am grateful that Elisa is feeling well enough to be quite physically active and to resume her university studies. My very best wishes are with her for a new year that will bring continued healing and renewed good health . I will be anxiously awaiting your update on the results of Elisa's March MRI and whatever treatment decision that is made based on your consultation with the surgeon and sarcoma specialist in Monteal. In the meantime, please take care, know that my special thoughts and deepest caring are with both of you, and keep in touch with the Board as you are able.
With Happy New Year best wishes, special caring thoughts, and continued Hope,
Bonni

Hello,

It’s been a while – again! - that we haven’t updated the board on how Elisa is doing. The short answer is: pretty good. She is still in the Cediranib trial at the NCI, and her situation has remained stable for more than a year now, with the usual but bearable side effects.

The CT scans in May and July might have shown minimal growth (perhaps 2mm) of one or two of the bigger lesions in the lungs, but this could apparently be due to the more precise imaging technique that is being employed now. Anyway, the last scan that was done in September showed definitely no growth. The last PET showed a bit more significant uptake in both the lungs and the thigh, but if we understand it correctly it is not necessarily very meaningful to compare these numbers.

Although these are altogether quite good news, we are starting to wonder whether Cediranib is still effective. Of course this is hard to tell, and I know there will be no clear answer to this question. It is simply quite frustrating for Elisa to continue to go to Washington (she has been going for 18 months now!) and tolerate the side effects without knowing whether Cediranib actually does any good, or whether her lesions would remain stable without it anyway. If Cediranib was already approved, we would think about switching to another similar drug for a while and eventually return to Cediranib. But since Cediranib won’t be available outside clinical trials anytime soon (I spoke with a representative of AstraZeneca Canada who was very pessimistic about Cediranib getting approval anywhere in the world…), this is obviously not an option. It is sometimes hard to have no long-term perspective…

With my best wishes to everyone,
Johannes

Hi, thanks so much for an update. It is awesome to hear that Elisa is stable. Is she allowed to ablate few nodules if they start to grow? It looks like some nodules might develop resistance while the other ones remain stable...
I have to say that in many cases when ASPS was reported stable with no treatment, in reality it was a very slow growth that is not detectable if you compare 2 consecutive scans and is only visible when compare with the 1-2 years old scans. We have been in this situation. Sometimes on the trials docs use REGIST criteria where the growth less than 20% considered to be stable...but I think it is not the case at the NCI, Dr. Kumar there is very honest and she tells if she sees the minimal growth - which is in my opinion is a good thing, otherwise the nodules could grow, be reported as stable and pose a big problem on a bigger size - and often can be very easily resected or ablated on a smaller size.

Dear all,

Just to let you know that nothing substantial has changed since our last update; Elisa is still going to the NIH, and everything seems stable. We managed to get an appointment for an MRI of her thigh for next week and will hopefully soon be able to see a surgeon with the images to discuss a possible resection of the primary.

Olga, regarding the possible resection of lung nodules, we haven't really thought about this, since (fortunately!) none of the nodules seem to grow. The images are always compared to several pervious scans, so they shouldn't miss minimal growth over a longer period.

Regarding the discontinuation of Cediranib, this means that a break and return to Cediranib outside the same study won't be an option for anyone. How stupid! I am not sure what we can do, but there must be a way to bring AstraZeneca and the FDA (and Health Canada, etc.) to, at least, give access to Cediranib to those patients who had a very good response to the treatment, within or outside a trial. Of course one of the problems is that there is no real interest in the trials anymore, so why should breaks from a trial, for instance, be allowed!? At the same time, why are Cediranib trials continued at all, given that the data is now close to meaningless?

Anyway, we'll keep thinking about what we could do and of course keep you posted.

Best wishes,
Johannes

Dear Johannes,
Thank you for writing to update the Board and for the VERY GOOD!! news about Elisa's continued stability . As I said in my personal message to you, it will be wonderful if Elisa's primary tumor in her thigh has now shrunk enough to be resected, but AstraZeneca's announced plans to discontinue Cediranib raises concerns that if Elisa needs to take the required break from Cediranib prior to and following surgery, she may not be able to resume taking Cediranib once she has recovered from the surgery. There are certainly many serious concerns and implications regarding the planned discontinuation of Cediranib for all of the ASPS patients who are currently involved in Cediranib Clinical Trials, as well as for those who were considering trying Cediranib at some point in the future and all future ASPS patients who may have benefited from it.
It is certainly perplexing why AstraZeneca just recently started a new double blind Phase 2 Cediranib Trial in England this Fall when they were apparently considering/planning to discontinue developing the drug any further. As you pointed out, it seems that it is an excercise in futility since the Clinical Trial data will now be of no value if the drug becomes defunct. I have been in contact with Yossi Landesman, founder of CureASPS, to try to determine if there is anything that we can do as an organization to appeal and reverse this very disturbing decision.
My very best wishes and most positive thoughts will be with Elisa and you for very good results from Elisa's next week's thigh MRI, and I will be anxiously awaiting your next update. Take care Johannes.
With special caring thoughts, healing wishes for Elisa, and continued Hope,
Bonni

Good evening everyone,

Just a short update: the last scans showed that everything is stable!

We are still waiting for the surgeon to get back to us; it won't be an easy decision whether or not to have the primary resected, but at least we should be able to take a decision that is a little bit more informed. At the appointment, the surgeon was definitely concerned that a resection might actually diminish Elisa's quality of life.

Of course we are taking into consideration that a drug like Cediranib might have better effects e.g. on the lung metastases with less overall tumour burden in the body... it all seems to be about balancing probabilities.

Johannes