'K' from USA - Dx 2007 at 10 years old

[Fictional]

Hi guys,

'K' had her day of scans today - and looks like we're back to "not as good as hoped, not as bad as feared". No slam dunk with the metronomic chemo which is now at 4 months (had been on weekly vinblastine, daily cytoxan, daily celebrex). First the good news - looks like no new nodules, primary has not grown back (now about 1.5 yrs after surgery) - but there is definite growth in some / most lung nodules left after surgery over the past 3 months (1-2 mm). A few may be 1 cm, the rest smaller.

Lots of options, but no definites -because most of 'K''s are still quite small (few mm), we are concerned that she wouldn't respond to VEGF inhibitor (also when we profiled a small lung met it was negative for VEGF and PDGF). We also have to factor in the issue that 'K' has been on Sutent at least 6 months before - and at that time, the little ones were still growing.

Mulling over several possibilities - Afinitor (Everolimus) is now approved, and seems to be promising - and actually Deforolimus looks even better (100% of sarcomas responded???), but that is a placebo phase III here in Seattle - We may look into the possibility of getting it "off-label" - if so, we would know that we really got it. 'K' is only 12 still - and entry requires age 13...so we would only be considered off-protocol.

We are also considering Gemzar, but the discouraging thing about Gemzar is that if you look at all the studies with Gemzar monotherapy, Gemzar looks as if it really doesn't work. Our onc told us that Gemzar was initially only able to be approved for 'pain', not for chemotherapy. So we're left wondering if it is a rare beneficial effect that Sarah had, especially as at least a half dozen ASPS patients who had Gemzar + something else didn't have benefit.

Ugg- more research...

[Olga]

'F', I do not know if you have seen it but we had a girl on Deforolimus in LA trial under Chawla superv. it was AP23573 then. She had a stable disease for about a year (?), her name was Pam, it was all on the old board. I have written to Dr.Kelly again. re gemcitabine but have not received anything again, may be you can do it? Our oncologist too says that she is skeptical re. efficacy of this drug overall but we just need to look into it more. There is one published article that our oncologist sent to us with the note that even though gemcitabine is a low toxicity drug it can be very toxic under the chronic administration:
International Journal of Surgical Pathology 13(1):81-85, 2005 Primary Alveolar Soft Part Sarcoma (ASPS) of the Breast Report of a Deceptive Case with Xanthomatous Features Confirmed byTFE3 Immunohistochemistry and Electron Microscopy
in this case they too used gemcitabine only but I am not sure what the result was its kind of vague I attached the PDF to this post let us see how it works
Also what about IFN?

[Fictional]

I will go look. It really is discouraging all this business - and at least we are thankful that there are no new ones and that nothing 'K' has taken seems to make it worse. We were in touch with John Goldberg again, and he thought maybe this degree of growth was "pretty good" - and that we might want to continue on metronomic for more rounds.

We would like to get Deforolimus if it weren't on study - but found a paper suggesting it caused stability in 25% of sarcomas - same percentage of benefit in a smaller study with Everolimus - so if it's hard to get, we will probably settle for a short trial of the one that we can get from Walgreens. It is stocked in a specialty pharmacy, but heard it will be covered by Premera. If 'K''s nodules continue to get larger - and the mTOR does not really cause stability (not RECIST stability, by mother's eye (me) stability) - we may consider revisiting TKIs and possibly cediranib.

The cediranib study for kids is still open in Washington DC - and I just heard because the NCI is funded by taxpayers, they will pay for the flight of one child and one parent- and come up with lodging. We could do this.

Also Rolle said he could go in on both sides in 'K' if he needs to too, but the problem is there are still a wide range in sizes (some very tiny ones)...I would think inevitably he would miss some if he went in too soon. Would like a med option as none of these are in critical areas.

Also have been reading more about the idea of sequential chemotherapy - there may be more benefit for this starting stopping-trying a new one than we realize. At least it's another theory and makes me feel better.

Clare also seems to be doing awfully well - and she did a lot of different agents including an HDAC a long time ago (would fit with the idea of sequential chemotherapy).

I would like to talk to our biotech friend - the transduction pathways are so confusing. There is now an FDA-released HDAC inhibitor too (so oncologist could just order), but I think with 'K''s Hif1alpha up in the latest profiling of her lung metastasis - the mTOR is a reasonable choice.

We are also not completely averse to doing a Sutent retrial at some point if her lung mets continue to grow to a larger size.

[Fictional]

I just wanted to update people with where we are and what we've learned about different agents.

We were all set to start RAD001, Afinitor - got it approved by Premera and sitting in the pharmacy, but I sat through all the webcasts on new sarcoma agents from the recent ASCO meetings and couldn't help but be impressed by R1507. Probably better for certain sarcomas (e.g. Ewings) than others - but did have an ASPS response and I know it has a low side effect profile (one high schooler has been able to continue cheerleading while on it). There is no MTD (maximally tolerated dose).

Little confusing how to find the trial because Roche number didn't know where sites were open yet, but the answer is to call the folks at SARC (sarctrials.org) and they will tell you who is active. We have to travel (drive weekly down from Seattle to Portland), but we are due to enroll next Monday in R1507. If all her numbers go well, she can get drug the same day. Nice to see some evidence of response by even 2 doses - though in the webcast, the ASPS response was shown at 3 months.

Also to correct a previous post, after getting K's final report, 2 metastases are now up to the 1 1/2 cm size (ugg) - but that gets us into the trial of R1507 and now we think 'K' is getting into range she could respond to VEGF inhibitors (BTW these were 2 nodules missed by Dr. Rolle, too bad, but even with laser there are limits to the technique). Several factors influenced our decision now for R1507 - relatively quick effect, rumor that sites for ASPS and R1507 may fill this week, low side effect profile (would be nice to have a good summer for 'K'). We also heard that 'K' could get a Cediranib spot at NCI for pharmacokinetics - but would have to be less than 13 at enrollment (she turns 13 in January) - so there was an incentive to prefer a quicker acting drug than slow in case we want to try Cediranib.

We are thinking we could always try others later (Afinitor/Rad001, Cediranib, pazopanib, some sutent combo etc), so the time seemed right.Will let you know how it goes.

[Fictional]

p.s. Also thinking about R1507 good now as 'K' is growing like crazy - was could see her a little taller each week when we were doing weekly metronomic...and insulin-like growth factors really spike at the onset of puberty. Anyway something to think about for kids around 'K''s age and sarcoma.

[Fictional]

Hi there, Not too much to tell you, but we heard that R1507 study was going to close for the ASPS cohort, so we got one of the last slots at Oregon Health Sciences. 'K' began July 27th. PET scan was negative before R1507, so we didn't have to do that again after starting drug. We have to drive down to Portland once a week (3 hrs each way), but we have gotten used to it.

No side effects, 1 hr infusion 1 to watch you, then home! 'K' had a great summer - running almost a mile every day, and now joined volleyball team. She is more fit now than she has been in a long time. She also passed her certification for golf - first summer since her diagnosis that she has been able to go through the full summer term of classes. Hooray!

I did notice that after coming off metronomic chemo regimen, her wbc count bounced back up (never was very suppressed, but was a little suppressed, wbc count dropped to 3.0) - and now her labs are all normal on R1507. I like her not to be suppressed at all. 'K' had her 6 week post-R1507 scan to day - and at least Seattle Childrens read says no change. Next scan will be in another 6 weeks - we will waiting eagerly as that was when the other ASPS patient saw some changes.

Sorry to hear Lucio stopped R1507, but we will keep on pushing on until it's evident it's not working. The possibles after: Afinitor, Pazopanib, Cediranib.

So that's it! Not too much to tell, and very happy that 'K' has had such a great summer.

[Amanda]

Dear 'F',
I am very happy to hear that she has had a wonderful summer and that her wbc is doing well. I too would also be watching the wbc and i hope that when i need chemo that i will be as fortunate as she is
My onc also spoke of "Afinitor, Pazopanib, Cediranib" and though i am far from looking forward to that point in my journey I at least know that these are now options and they are seeming to be working well I called again to see if they would allow me in the Cediranib trial and they said till i am not stable that i may not enter the trial *sigh* But, the main reason i called was to ask the nurse at the Cediranib trial when they would be opening this to our children and expressed sadness that it had not yet been opened! I am hoping that this trial with just the one drug will prove to be what we are all wishing for!
I am amased at the wonderful and strong and positive children we have with ASPS and they are a role model for myself in so many ways even if i have never met them face to face.

I hope that Fall will bring happyness and healing for 'K'..

In healing hopes and cures for everyone!

AmandaR

[Fictional]

Thanks Amanda and all the rest.

Nice P.S. to add today, too. Seattle report just said stable, no new ones - but Oregon Health Sciences identified 3 "index" lesions over 1 cm that they measure and follow - well it looks like one SHRUNK! (from 1.3 x 1.5 cm to 1.3 x 8 mm) That's nice! Other 2 - no change.

Also found out that 'K' has put on some weight - so she will have a higher dose next week.

We especially like that there are no side effects.

I used to think that maybe who cares if something shrinks but it does not go away entirely - or if something shrinks and other things grow who cares - but with the recent research about stem cells in solid tumors, I think I had it wrong. Some cells are really worse within a solid tumor - the ones that have higher proliferative potential and the ones that can metastasize (cancer stem cells). Among the 10-20+ survivors of stage IV ASPS, I've been impressed by the number who still have nodules that just stopped growing...attributed to 'scar' or dead tumors - but maybe these are still residual ASPS that had the worst cells killed off...or dormant cells as others mights say. Anyway, I'm more of the mind to think any dying tumor cell is a good tumor cell, if you know what I mean...

Another interesting aside - in the previous 6 months, every month 'K' had been taller with every monthly check (growing like a weed) - and alkaline phosphatase I found out can be a marker of growth spurt (norms are higher in preteens)...now on IGFR2 Ab (inhibit growth), 'K' is not any taller with the monthly check and her alkaline phosphatase has gotten smaller with each weekly blood draw. IGFR inhibitors are of particular interest in childhood cancers because it is thought that the growth factor spurt in IGFs with puberty cause solid tumors to growth faster. But the 1 ASPS case we know of at the ASCO meetings that had a lung met shrink with R1507 was in a 31 year old, so not necessarily just for kids.

[Fictional]

Oops! Probably spoke too soon. The report from OHSU says one shrunk, but when I looked at films - this was probably never a met - not a balloon or bowling ball like thing, but rather a nodular-ish scar that actually used to be a hole from Rolle's laser. I never thought that was a met - they are not used to looking at laser, and radiologists generally will only compared to 1 scan prior as a general practice. They didn't see how that area developed - it was not smooth like the other 2.

This, by the the way is a caveat. This is how suddenly patients discover they have large mets that were "there for months before etc."

Well at least now growth. Seemed like everything was growing at least a little on metronomic before.

So R1507 at 6 weeks: no growth, no shrinkage.

[Bonni Hess]

Dear 'F',
I am so happy that 'K''s six week R1507 status scan showed no new tumors and no growth, and that she is tolerating the medication so well with no negative side effects. I will be holding very tight to Hope that the next scan will show continued stabilization of the disease and shrinkage/necrosis of her lung mets. In the meantime, I Hope that she continues to feel well and that she is enjoying a wonderful beginning to the school year. Please drive safe on your weekly treatment trips to Portland, take care, and have a beautiful Fall.
With special caring thoughts and continued Hope,
Bonni

[Fictional]

'K''s scans were stable today - Hooray! We like the stuff. We're staying on. 'K''s been able to be full time at school and even play on her volleyball team after school. NO side effects!

The formal report says no new ones and stable to minimal increase in a few. When I looked at the films, her largest ones (over 1 cm) didn't change. A few small ones actually seemed to shrink, and a few small ones seemed to grow slightly. She's completing week 12.

Tricky judgment call because we will probably pass on the last spot for a pharmacokinetics trial with cediranib in kids. We would consider Afinitor or pazopanib as a next step, but thankfully we can put off the decision again for a little while. There is some indication that Cediranib and Pazopanib may be FDA-approved as early as the second part of next year...

: )

[Bonni Hess]

Dear 'F',
This is wonderful and very encouraging news! Please know that I am sharing your great relief, joy, and strengthened Hope, and sending best wishes for continued disease stabilization and tumor shrinkage.
With happy hugs, special caring thoughts, and continued Hope,
Bonni

[jcs2007]

I am very happy to hear 'K' had stable scan and experiencing no side effects.
That is so important when they are still trying to have a "normal" life with
sports and school. With the drug, do you know how long she will have to
keep taking it? Well, thanks for sharing your update!
Blessings to all who are on this ASPS journey,
Cindy

[Fictional]

Hi everybody,

Brief update for you all. Stable scan - no growth and no new ones. Yay! 'K''s completed 18 weeks R1507 and we hope to coast on this as long as possible. No side effects, but have to be in the clinic once a week for an hour infusion through her portacath. No shrinkage, unfortunately, but we're thankful for what we have. Actually the trial is recording a shrinkage of one lesion they called "scar vs. nodule", but we're pretty certain it is a scar after one of Rolle's surgeries.

We're now 1 year 3 months out from Rolle surgery on the R lung and 9 months out from surgery on the left.

We are hoping these things may be going dormant.

Hope you all had a good Thanksgiving holiday with your families. We're keeping you all in our prayers,

'F'

[Amanda]

Hi 'F'
YAY! great news!
I am very glad to hear that she is doing so well! What a wonderful gift for the holidays!
If they have been stable that long wouldnt it mean that they are dormant or necrotic?
I pray that this is what is happening and that you all have a wonderful holiday season!

In healing hopes for all!

Amanda