LCMA - Dx 2007

[Olga]

I have a comment re.cediranib - you can not really demand it from any oncologist for now, it is only available on a clinical trial at the NCI at Bethesda (and this is the only ASPS specific clinical trial at the moment). I am wondering if your current oncologist is aware about this clinical trial. They are always very overloaded with the patients. NCI folks on this trial is very open for the communications so they can discuss this between them, but some of our people got there by the self referral too and they did not decide if they are going to start this trial, the decision about eligibility is ultimately up to the clinical trial team. But the spinal met would probably have to be treated before of the trial if you decided to proceed. In general, in my opinion the value of this trial is different in different situations.
I have a question about the resectability - have you ever considered/consulted re. possible resection of the lung mets?

[skyflower]

Hi LCMA, are you continuing to take Sutent or are you completely off while you decide your next steps? I was wondering if the doctors had thought about increasing the dose during the interim to see if they can get a continued stability or if that idea is just dumb?
-lokelani

[Fictional]

LCMA,

I also thought I should add that although in the past Nexavar didn't work for a few people with ASPS in this forum, that at least in renal CA, oncologists found that if a person responded well to one of the VEGF inhibitors - that when they stopped responding but were switched to another - they tended to have a good response to the second one. So just because someone with ASPS didn't respond to Nexavar as a first VEGF agent, it doesn't mean it's exactly the same situation as being on Sutent x 2 years and then switching to Nexavar...get it? In the renal Ca research (another solid tumor), it looked as if a good response was seen no matter what 2nd VEGF inhibitor was tried.

Whenever you are one drug for a long time, the chemistry changes - so if you develop tolerance to one agent, switching to another can still make sense.

I had that powerpoint somewhere. If I find it, I'll upload the data if you want to see it.

[Fictional]

Ok here it is. Figlin is the guy.

The data are pretty impressive. Kidney cancer does have a significant overlap with ASPS in that it is often a metastatic vascular solid tumor and some of the transpositions are very similar to the one in ASPS. It is different from ASPS in that it tends to be more rapidly progressive - so keep that in mind when you look at progression / survival numbers.

Figlin basically found out that things stayed stable whether you did Sutent then Sorafenib or Sorafenib then Sutent, etc.

[Fictional]

Oh and I almost forgot. Anders or maybe someone else posted this abstract about other VEGF inhibitors and ASPS - and one patient was on Nexavar and it kept him/ her stable for 5 months...as mentioned - it might be even better if another VEGF inhibitor had been used before. It might be that one VEGF inhibitor triggers increases in another subtype - so switching reinforces stability. Everolimus also looks like a good one for ASPS.

New therapeutic options in the treatment of alveolar soft part sarcoma (ASPS)
Bertz J, Pink D, Busemann C, Bitz U, Richter S, Rahm J, Schoeler D, Reichardt P

Background: Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor
often occurring in young patients. Although it shows an indolent slow-growing clinical
course, its prognosis is usually poor, especially if complete surgical resection is not
possible, with a characteristic late appearance of metastases. Since standard
chemotherapy regimens used for the treatment of other soft tissue sarcomas lack
efficacy in ASPS, new therapeutic options are needed. Recently, responses to
sunitinib were reported in three patients.

Methods: All patients with metastatic ASPS that were treated in the last 4 years in the
Sarcoma Center Berlin-Brandenburg and the University Hospital of Greifswald were
screened for “new treatments” in our sarcoma database of more than 2000 sarcoma
patients. 8 patients with ASPS were treated with either Trabectedin, Everolimus or
the multi kinase inhibitor Sorafenib. Of 6 patients receiving Trabectedin, 3 patients
had been pretreated with conventional chemotherapy, one had been treated with a
monoclonal IGF1-antibody and two patients received Trabectedin as first-line
therapy. Everolimus was given once as first-line therapy and twice after progression
under other chemotherapy. The application of Sorafenib was realised in one patient
as third-line therapy.

Results: One patient treated with trabectedin is too early for evaluation. In all other 5
patients, a disease stabilization (SD according to RECIST) was reached under
treatment with trabectedin. Median progression free survival (mPFS) in these 5
patients was 7 months (3+, 4, 7, 14, 23 months, respectively). All three patients
treated with Everolimus are still alive. One patient progressed after 9 months, and
two are stable on continuous treatment for 18+ months. The application of sorafenib
resulted in disease stabilization lasting 5 months in one patient. All of the above “new
treatments” have been well tolerated with no high-grade toxicity.

Conclusions: The poor prognosis of patients with ASPS is due to the unavailability of
effective systemic treatment options. We report about three new promising
therapeutic options in patients with ASPS: Trabectedin, Everolimus and Sorafenib. All
three agents seem to have antineoplastic activity in ASPS and are able to induce a
stabilisation of the disease.

[Ivan]

I'm not sure 5 months can be called any sort of stability with ASPS - at least in my case. Sometimes what would happen is they would say it's stable from one scan to the next (5 months), and then all of a sudden by next scan there is progression (another 5). Of course, it was growing slowly all along, but radiologists don't report less than 10% change in size. It's probably different with clinical trials, and they have specific guidelines on what's considered progression and what isn't. Typically, how much growth would be required to get kicked out of a trial?

[Fictional]

These are people's personal threads and personal choices about treatments should be up to them and their doctors who know their history in detail. Too much negative 'karma'. Even though some of you are well meaning, the posts are challenging and not supportive - isn't this supposed to be a support group?

Maybe we can have pro and con thread of the different choices for drugs. It seems to be a different situation switching from one antiangiogenesis agent to another. If you inhibit one combination of VEGF receptor - and other other compensates, then adding one with a different class or response may get the tumor more in check.

Most common molecular profiling doesn't specify between the subtypes of VEGF receptor. Usually its immunostaining for the VEGF (the ligand) and not the receptor. The theory makes sense and in larger trials (albeit with a different solid tumor), the data also support the rationale.

[Ivan]

These are people's personal threads and personal choices about treatments should be up to them and their doctors who know their history in detail. Too much negative 'karma'. Even though some of you are well meaning, the posts are challenging and not supportive - isn't this supposed to be a support group?

Maybe we can have pro and con thread of the different choices for drugs. It seems to be a different situation switching from one antiangiogenesis agent to another. If you inhibit one combination of VEGF receptor - and other other compensates, then adding one with a different class or response may get the tumor more in check.

Most common molecular profiling doesn't specify between the subtypes of VEGF receptor. Usually its immunostaining for the VEGF (the ligand) and not the receptor. The theory makes sense and in larger trials (albeit with a different solid tumor), the data also support the rationale.

I don't think I am being negative, just asking for clarification regarding what is typically considered stability in trials. Since I've never been on a trial - how much change in the measurement is considered sufficient "growth" to be kicked out of the trial? I am sure if it's 5% it's considered stability.

I know that if I had scans every 3 months it would have been "stable" for the whole of the seven years scan-to-scan. Which, of course, is nonsense caused by the fact that typical stability guidelines do not apply to such slow growing tumors as ASPS.

[Olga]

In the article from Germany mentioned above the authors said that they used RECIST to evaluate the response, the general guides how to use RECIST can be found here:
http://imaging.cancer.gov/clinicaltrials/imaging/
but overall if the progression is less then 20 % it is classified as the SD under RECIST (if there are no other responses). So Ivan is right, for ASPS the growth less then 20% in 5 month is a very common thing and in my opinion does not deserve any mentioning in the article - unless the patient had the faster progressing situation before of the treatment and the reporting doctor on that trial/treatment is aware of it and it may explain that he decided to report this result as significant.
In any case, LCMA - even if we disregard the case described in the article as a supportive for use of the sorafenib in ASPS -let say that the evidence is weak, but there is no evidence it doesn't work. It still have a chance to be helpful in your situation - you had the good long lasting response to sunitinib so you might get it to sorafenib as well. There are probably only few people with ASPS that were taking sorafenib overall and to say at large - we do not have enough information to assume its efficacy or inefficacy, so we will hope for the best result.

[Bonni Hess]

Dear LCMA,
I think that Olga mistakenly thought that Dr. Loeb was your former oncologist that you felt so much confidence in who has now moved to California. As I understand it, Dr. Loeb is the oncologist in Maryland from whom you are seeking a second opinion.
I Hope that you are tolerating the Nexavar (Sorafenib) treatment well, and I am holding very tight to Hope that the Nexavar will be able to re-stabilize your disease progression and cause tumor shrinkage/necrosis. If it is effective for you, it will be especially encouraging to everyone who is currently on, or has previously been on Cediranib or Sutent to know that there is another anti-angiogenic medication which may help to re-stabilize disease progression if resistance is developed to the Cediranib or Sutent. I will be closely following your Nexavar treatment experience, Hoping for a very successful response, and anxiously awaiting your updates regarding your side effects and scan results. Take care LCMA and keep in touch with this Board as you are able.
With special caring thoughts, healing wishes, and continued Hope,
Bonni

[Olga]

Right, I saw that you said "Sent my information to Dr. Loeb today" so I decided that you sent the latest cans to your former oncologist that you liked, we often send Ivan's scans to Dr.Rolle (and the last one also to Dr.Littrup) so I just assumed that. What was the name of the onc. that you had before and that moved to California?

[Bonni Hess]

Thank you for the thoughtful update LCMA. I am so grateful that your labs were stable, and am Hoping that you are continuing to tolerate the Nexavar well. I am glad that Dr. Loeb concurred with the decision for you to try Nexavar. Regarding your small met on your lumbar vertebra, has it increased in size at all since it was originally diagnosed? I think that the decision not to radiate it is probably a good one since ASPS is so notoriously resistant to radiation, which was confirmed to us by Brittany's heartbreaking failed radiation to her cervical/thoracic spinal tumor. Hopefully the Nexavar will be successful in shrinking your lumbar met, or at least in preventing it from growing any larger. How often are monitoring scans done to determine the effectiveness of the Nexavar, and when are your status scans scheduled? I will be anxiously awaiting your next update, and holding VERY tight to Hope for good news of stable disease and tumor shrinkage. In the meantime, please take care and know that you are held very close in my heart and thoughts.
With special hugs, deepest caring, healing wishes, and continued Hope,
Bonni

[Olga]

LCMA, I wanted to ask you how this lumbar met was found and is followed - was it chest CT or MRI.
We have very limited info about the ASPS spinal mets behavior and possible treatment outcomes, we only had a couple of cases here on the board and there is not much info in the published literature either.
On the side note, there are different types of the radiation treatment and although ASPS mets are usually not sensitive to the conventional radiation doses (and as I understand this is what Brittany had since the tumor was to big for the radiosurgery) they are more sensitive to the doses that are given with the radiosurgery (for example we know about many successful cases of the ASPS brain mets treated by the radiosurgery GammaKnife), when high doses are focused on a small met and practically burn the target. Radiosurgery can be only done on a small met.

[skyflower]

Hi again LCMA
i hope these second opinions are offering you piece of mind with your personal treatment decisions, especially enough to maintain a positive attitude
have you tried calamine lotion for the bumps? does hydrocortisone interact with nexavar or is it a just-in-case type situation?

[Olga]

LCMA, if you feel good physically it means a lot - that your disease is not advanced yet, that your body has a lot of resources and whole array of different treatments can be used if they are applied without delays at the right time and not when the disease is already so advanced that some treatments can not be used optimally. Scanxiety is no easy for all of us but again - you feel good and it is the good sign.