Josh,
I am glad that there is no significant change in your right lung. That should be good news? I can only tell you about chemo what we expierenced with Tok. Dr Cohen suggested the MAID treatment i.e: Dacarbazine, Doxorubicin, Ifosfamide and Mesna. These four drugs were given to him over a period of 96 hours. He was admitted to hospital and stayed there for the four days.
This was not an easy option but under the circumstances the best option for Tok as we don't have clinical trials etc.
I truely hope this could be of some use to you.
In the meantime keep up Hope, Josh.
Take care of yourself and well done on doing your excercises and keeping a positive attitude.
Josh, chemo-sensitivity testing is interesting but it is not always right in a practice - probably because of the interaction between the tumor and the body, on the other hand it is may be at least some reasonable starting point.
I think we had a temozolomide experience between our group a long time ago, I can not remember though if there was a response. Out of your list, one patient had a fantastic outcome with the gemcitabine (read in success stories). It is hard to say anything really if there is no information as the medicine is a statistical science.
Olga:
From what I understand, this test decodes the DNA of the tumor and looks for certain markers, then compares other cancers with similar markers that have shown reaction to certain chemotherapies to help provide educated guesses on what might work. Of course, this is conjecture on my part based on staring at several articles and understanding every 3rd word.
As far as I know, there was no actually study of chemo drugs on cells done. But, as I said, I could be totally wrong here. Here is the company's site, which I didn't find especially helpful in understanding. http://www.carismolecularintelligence.com/
Well, my insurance has agreed to pay for Temozolomide. I am calling my onc now to see if he wants me to fill it, as I haven't discussed Dr. Rolle's plans with him yet. I am nervous because I haven't been able to ask him about the dosage, and I don't think that it makes a lot of sense to pursue an aggressive chemo regimen, but am not sure if the dosage he prescribed is considered aggressive or not. I certainly don't want to cause any kind of immuno-suppression, so I am hoping he agrees to start me out on a light regimen, if possible. Just a guess, but I think the reason he chose it is because it is a pill vs. IV and he thought it best to start with something easier to take.
As I understand it, Temozolomide works by focusing on cells which divide quicker then normal (and this is how it distinguishes between cancer and healthy cells) but, as we all know, ASPS is a slow growing beast, so I am hesitant to try this. I need clarification on what the dosage he prescribed is going to do to me.
The Gemzar is very tempting, considering the success case that Olga referenced, but I know it's not always wise to base a decision on a single case. I believe Gemzar is still IV only, so that would be an additional burden.
I have also contacted Dr. Federman at UCLA who has agreed to see me for a 2nd opinion, but I know he doesn't agree with prescribing traditional chemo for ASPS. I would like his advice and to have him on my team, but really can't afford to fly to LA just to have him tell me I should go on a TKI.
I'm hoping Dr. Rolle hasn't forgotten about my email I sent a week or two ago; I haven't heard back from him. My main concern is whether these nodules are actually regrowth or just something he missed or even scar tissue...Maybe he can't tell until the next scan is done?
Just kind of thinking out loud here...I may come back and edit this post for clarity later lol...
Ivan:
I do. We recently switched the location where we get scans done, which may have been a poor idea, as they use different model of machines and the radiologist has already commented on the difficulty this causes in readings. Also, the new place is very difficult to request that they send scans where we need them, so I may switch back.
They also use a different format to save the scans in...with the old place, I was able to set it up on my PC so I could save the scans to my hard drive and mount them as an .iso image. That makes it so that I don't have to lug those discs around (also, they open much, much faster due to HDD being faster then CD-ROM). The new place uses some fancy format that I haven't figured out yet.
You don't need to create ISO's, you can just copy the discs' contents into separate folders on your hard drive. Then, you can use this - http://www.microdicom.com/ - to compare the two scans. Run two of them side by side at once, that makes it easier. The cool thing about this software (other than that you can run more than one instance easily) is that it allows you to measure to a fraction of a millimeter which can come in handy sometimes. Also, you are not tied to the viewer software included on each disc which sometimes renders the underlying images slightly differently.
I usually compare to a scan from a while ago (2 years), since 6 month is often too short to see appreciable growth. I've itemized every nodule in my lungs and just re-measure it every time I get a new scan now.
Dear Josh,
I have been away from the Board for the past month due to a devastating family tragedy, and I am just now getting a chance to try to catch up.
I am wondering if you have decided to go forward with the Temozolomide (Temodar) systemic treatment, and if so, on what basis you decided to pursue it? Did your oncologist provide you with statistical/anecotal information showing that Temozolomide has been successful in treating ASPS specifically? I am asking you these questions because when Brittany had her brain mets, her radiation oncologist strongly recommended Temodar since it is a drug that can cross the blood brain barriar, but when we requested statistical data to support his recommendation and document Temodar's effectiveness for ASPS, he said that there was none available at that time (which was several years ago). Since he was only able to offer us a small percentage chance that Temodar might be successful in stabilizing the progression of Brittany's disease and preventing her from developing more brain mets, and since he told us that Temodar would result in Brittany being infertile and unable to have children, we decided against this treatment for her. Of course, each patient may respond differently to different drugs, and this treatment might be successful for you, and Hopefully it will be if you decide to go forward with taking it. I just wanted to make sure that your oncologist has given you a good rationale for prescribing it for you, rather than just taking a stab in the dark with something that may/or may not have proven success for ASPS.
The following is an article about Temozolomide from the April 2013 edition of E-Sun, the Sarcoma newsletter, which might be interesting for you to read.
Stage 1 testing of temozolomide
The DNA methylating agent temozolomide was developed primarily for treatment of glioblastoma. However, preclinical data have suggested a broader application for treatment of childhood cancer. In this study, Temozolomide was tested against the PPTP solid tumor and ALL models. Temozolomide was tested against the PPTP in vitro panel at concentrations ranging from 0.1 to 1,000µM and was tested against the PPTP in vivo panels at doses from 22 to 100mg/kg administered orally daily for 5 days, repeated at day 21. Results were as follows: In vitro temozolomide showed cytotoxicity with a median relative IC50 (rIC50) value of 380µM against the PPTP cell lines (range 1 to >1,000µM). The three lines with rIC50 values lesser than 10µM had low MGMT expression compared to the remaining cell lines. In vivo temozolomide demonstrated significant toxicity at 100mg/kg, but induced tumor regressions in 15 of 23 evaluable solid tumor models (13 maintained CR [MCR], 2 CR) and 5 of 8 ALL models (3 MCR, 2 CR). There was a steep dose response curve, with lower activity at 66mg/kg temozolomide and with tumor regressions at 22 and 44mg/kg restricted to models with low MGMT expression. Conclusions: Temozolomide demonstrated high level antitumor activity against both solid tumor and leukemia models, but also elicited significant toxicity at the highest dose level. Lowering the dose of TMZ to more closely match clinical exposures markedly reduced the antitumor activity for many xenograft lines with responsiveness at lower doses closely related to low MGMT expression.
Take care Josh, know that my most caring thoughts and very best wishes are with you, and keep the Board updated as you are able.
With deepest caring, healing wishes, and continued Hope,
Bonni
Bonni, thanks for the link. Did you understand this sentence:
Lowering the dose of TMZ to more closely match clinical exposures markedly reduced the antitumor activity for many xenograft lines with responsiveness at lower doses closely related to low MGMT expression.
I assume TMZ = Temozolomide? What is meant by "lowering the dose to more closely match clinical exposure?" I know a xenograft is when a tumor is basically introduced into a mouse or other lab animal...is it saying that low MGMT expression means that Temozolomide seems more likely to cause an antitumor effect? It seems like a few well placed commas would clarify that sentence greatly.
I still haven't started any treatments. It has proven difficult to work doctors appointments around work hours, and I am hesitant to take days off, considering I don't know if these treatments are going to cause me to have to stay home or if they will be tolerable at work.
June update:
My recent CT scan showed a few tiny new nodules on the right (unoperated), while the left (operated) is still hard to read from the surgery, but appears mostly stable. There is a larger object that I am confused about in the left near the base that appears to have grown, but it is an odd shape, not circular at all, so I hesitate to call it a met. It was 1.7cm on the March scan and it is now ~1.9 cm in size, which means it would've had to have grown almost 2cm since January. I am waiting on Dr. Rolle's reading of the scans for a definite answer, but Dr. Federman called it mostly stable with a few new small nodules. He has suggested that I take a 3-4 month trial of Pazopanib and then take 3-4 weeks off and then return to Germany. This would put me back in Germany early October, if Dr. Rolle agrees.
I always felt like it was a good idea to take some treatment prior to the surgery; it will hopefully show necrosis to prove/disprove efficacy. However, my concern is: is it infeasible to look for necrosis from a TKI? My other concern is that I will upset the relative stability that I have been experiencing. I don't want to poke the proverbial beehive, but I don't want to sit and wait and waste valuable time either.
Any thoughts on this?
I am filled with hope that everyone is doing well!
There is a larger object that I am confused about in the left near the base that appears to have grown
You have to locate an earlier scan right away. 1.7->1.9 is questionable. If you can see it being smaller, like around 1 then you know for sure it's a met. Mets don't have to be spherical. They can be of various shapes, especially when adjacent to something else.
Back when I was stupid(er), I noticed something like that as well. A year later it ended up being that largest met adjacent to the heart which cost me $10,000 to get re-ablated in Detroit (after a failed ablation in Vancouver), and put me at a significant risk of needing a thoracotomy. In retrospect, that was ridiculously stupid.
Josh, I assume that you meant to write "it would've had to have grown almost 2mm since January." not 2 cm?
About the possible mode of action with TKI and if you should try Pazopanib. I am not sure what is the reason it is recommended to you, what is the oncologist trying to achieve? Medicine is a statistical science and any recommendations should be evidence based. What is his recommendation based on?
The phase 3 clinical PALETTE trial found "lack of overall survival benefit was the occurrence of a “rebound” effect that accelerated progression after patients stopped pazopanib therapy". The trial was done on sarcomas in general not ASPS and I have no idea if ASPS as a group will have more favorable outcome on pazopanib - if it is going to increase the OS or not.
Some people will def. benefit from the drug - to shrink a tumor to allow resection or other treatments, to buy a better quality time when there is a fast progression and the patient is symptomatic etc.
and tell me what is your impression and if my conclusions look reasonable. As I can see, the authors declare no conflict of interest and they conclude that " It is clear that angiogenesis has a critical role in STS, but further work is required to understand mechanisms of resistance and identify biomarkers of drug efficacy, as well as effectively and safely combining pazopanib with other agents targeting pathways that may be implicated in pazopanib resistance. Current and planned trials are evaluating pazopanib in combination with other agents as well as in the neoadjuvant setting."
In short, there is no proof that pazopanib increases ASPS patients lives. It may be will in combination with some other drugs. If you want to try something, I would suggest to do it appropriately - when/if there are no other radical options left (surgery, ablation) and in a setting of a clinical trial, which should be picked very carefully too.
