Cure Alveolar Soft Part Sarcoma International (iCureASPS)

I copy this part from Lucio personal updates, please add here as the new information or comments became available:

Lucio started the Cediranib trial at the NCI in late October. They put him on 30mg per day, and on December 14 we received the good news that his largest met (close to 2cm) is now 40% smaller! We're not sure how much the other Mets have shrunk as we don’t yet have the report or the slides, but obviously this is great news for all of us.

So far everything has been okay except for his bilirubin. On weeks that he travels to the NCI for clinic his bilirubin count goes above 1.5, and this is a concern for them. We think it has to do with traveling to the NCI from orange county, ca. Maybe the stress makes the difference because when he has labs done in California his results are fine. He’s also noticed on days when he travels he just feels crappy, even for a few days after.

His side effects have been mild to moderate. Here’s a list of the most common side effects, he gets these just about every day:

Diarrhea
Painful abdominal cramps
He’s become more irritable (This came from him, not me! )
Constipation
Fatigue
High blood pressure

Less Common Side effects are:

Cold Sweats
Sensitive hands

Feel free to ask if there's any questions!

Dear Lucio,
I Hope that you are continuing to tolerate the side effects of the Cediranib, and that your bilirubin levels have stabilized. Has your participation in the Trial been affected by the temporary hold that has been put on the NIH Trial because of adverse side effects experienced by a couple of the patients? Also, if you have contact with any of the other patients currently participating in the NIH Trial and if they are not already familiar with the CureASPS organization, could you please tell them about the CureASPS.org Web site and encourage them to visit the site and update the Board with information about their Cediranib treatment experience and results because the shared anecdotal information about this treatment is so vitally important to all of us who are closely following the Cediranib treatment outcomes. My best wishes are with you for a continued successful response to your Cediranib treatment, and I will be anxiously awaiting your next update. Take care.
With special caring thoughts, healing wishes, and continued Hope,
Bonni

Thanks Bonni

My participation in the trial has not been affected because of the complications of other participants. Everything is going as scheduled and I have a CT scan this coming tuesday to confirm my 40% partial response. As far as meeting any asps patients, I have not. I'm usualy the first person there on mondays so I'm in and out before most patients get there. Yvonne did mention a gentlmen who had a 30% partial response while in this study(this man also showed very little side effects) but I dont know his name or if he post on this forum.

Thanks for your support, and I will get back to you guys when I get back from Maryland.

-Lucio

Dear Lucio,
Thank you for your thoughtful response and for the shared information. I am so grateful that your continued participation in the NIH Trial has not been affected by the temporary closure of new patient enrollment. My special thoughts and very best wishes will be with you for your scheduled Clinical Trial status scans next Tuesday, and I will be anxiously awaiting your update. If the opportunity presents itself, and if your time and the situation allow, it would be wonderful if you could give the name and Web address of the CureASPS.org Web site to the Clinical Trial oncologist or nurse and ask if they will share it with other ASPS patients who are participating in the Trial who might be interested in visiting and participating on our Discussion Board. Please take care Lucio, travel safe, and know that my best wishes and continued Hope travel with you.
Bonni

Sory about the late update. All I can say is that not much has changed since my last update. My partial responce was confirmed by my lates ct but I do not have the exact details rite now since I've moved last week. I still havent unpacked and sorted everything out. I have another CT and PET coming up next week. I will post if anything important pops up but if nothing realy changes I will probobly lag like I didn this time.

Dear Lucio,
Thank you for your thoughtful update in the midst of being so busy with unpacking and trying to get organized and settled from your recent move. I Hope that you are continuing to tolerate the Cediranib well with minimal side effects. My special thoughts and best wishes will be with you for your next week's scans and for results which show continued disease stabilization and tumor shrinkage. I will be anxiously awaiting your next update when your time allows, but in the meantime, please take care and enjoy your new Home.
With specail caring thoughts, healing wishes, and continued Hope,
Bonni

Hi everyone


Next Monday I start my 8th cycle on cediranib. My most recent CT scan showed basically no change since my last scan. My last scan basically confirmed the partial response I had in December. Dr Spinoza said there is a small amount of shrinking but it was very little. The most concerning met and the one they are watching very closely was originally 22 mm. My first set of scans showed this met now measures 10mm and is no longer in contact with my heart, aorta, or bronchi. This is good for me cuz Dr Lee (ucla) said resecting this met could require a lobectomy because of the proximity to major airways. It’s the only met I have now that is not on the periphery of my lungs. There is also one met that is down to 9x6 from 11x8, another that is at 6 from 8, one that is at 6 from 9, and finally one that is 13x8 from 14x11.

FYI. Dr Spinoza said they way they measure the response is they sum up all the diameters of the mets they’re monitoring, and compare them to the diameters of the latest scans.

** SIDE EFFECTS **

I list these in order from worst to um “least worst”….

1. Abdominal Cramping: During the first few cycles of my study these cramps were mild to moderate usually occurring about 4 times per week mostly an hour or two after lunch. Now these cramps range from mild to very painful and they sometimes last for several hours at a time. Now I am getting them at least twice a day but on bad days I can have cramps throughout the day. Having bowel movements and also passing gas helps to ease the cramping temporarily. Last week Yvone prescribed me some dicyclomine but to be honest things haven’t changed much. The only thing that helps me cope with cramps when they kick in is Oxycodone.

2. Fatigue: For the first 4 to 5 cycles my fatigue was mild. But as of the last two cycles or so thing have changed dramatically. I now have a Doctors note saying that I need a flexible start time at work, and it has worked out to an approved 11 am cap, and even that is hard to do sometimes. Most days I wake up around 10 or 11 am and it’s very hard to get up. Also, I’m not sure if this is related to my fatigue but I’m just not that with it anymore. My head is just not as alert as it used to be. Sometimes I miss turns when I’m driving and sometimes I just can’t concentrate on tasks that require reading comprehension. I’m not sure if this has to do with the Fatigue or if it’s just a result of being on so many meds all the time.

3. Diarrhea. Yep, rounding out the top three is good old Diarrhea. During the first 2 cycles or so it was really bad because I still didn’t know what types of food irritated my bowels and caused extreme episodes of diarrhea. After that I figured out what to avoid and what to eat more of I got it under control for the most part, even with out using loparimide. Recently though, things have gotten worse and I’ve started using loparimade with more frequency. It’s worked okay but sometimes I still have bad episodes like going 8 times a day.

4. Body aches, chills, and hot flashes. I bunched these together because they usually occur together and sometimes they occur with night sweats. Usually these effects only last for about an hour or two per day, but if I get them at night its hard to fall asleep and I end up feeling really bad the next day. I’ve managed the body aches with Oxycodon and that’s worked okay for the most part.

5. Other side effects include short migraine head aches, nausea, acid reflux, and mild hand and foot syndrome. These are usually mild to moderate and I manage them with Tylenol, and tums.

So far the biggest concerns they have with me is my Bilirubin, its been above 1.4 (total) on at least five occasions. Also there have been red blood cells in my urine and I think once or twice there was an elevation in liver enzymes but nothing major.

I have noticed a slow but steady increase in the severity of my side effects. Usually things get worse when I travel. A few weeks ago I had a business trip to Seattle and I was there for 2 weeks. I got really sick when I was there and I got the go ahead to stop taking the drug for two days. After my 2 day “holiday” I noticed an improvement in all my side effects. I don’t like the Idea of skipping doses because I don’t want to go easy on my mets, but to be honest, for the last 6 weeks I’ve been thinking about getting my dose reduced to 20 mg because if things continue to get worse I don’t think I’ll be able to continue to work full time. I’m totally prepared to leave work if I need to but times are tough and I really don’t want to stop working unless I “have” to.

Another concern that I have is that since December there has been no real change in my scans. From what I’ve read most people, including myself, experience the most significant changes early on. Does anyone know if there have been any good responses to the treatment after 7 cycles? I’m just trying to figure out if I should stay on the trial for much longer or if I should try to resect that dangerous met while it’s still small and not touching any surrounding structures. I’m going to see what Dr Lee thinks but I’m open to all suggestions because I want to explore all possible scenarios.

If you guys have any specific questions please post or PM me and I’ll try to address them as soon as I can.

Thanks again, sorry for my delayed update.

Lucio - thank you for the update and for the very thorough report on the side effects, I am sure that all people that are on the trial appreciate it a lot as this board the only source of the first hand information on this very rare subject.

Are you still on the 30mg per day? I am wondering if the efficacy of the drug might be the same if the dose is lowered to 20mg, because as I understand they decided on 40mg being the max tolerated dose but it is not necessarily means that there is direct link between the max tolerated-max efficacy. It might as well be working at the lower doses with the much less toxicity? I would probably try that, I personally have my experience with the anti migraine drug Imatrex that I take half of the recommended dose and despite my migraines being very severe it works the same at the half dose and at the full dose, it is all very individual I think, depends on how much of the targeted by cediranib substance is produced by your tumor.

On the other hand the surgery would have been my first choice as long as it can be done and I would keep in the close contact with the surgeon so he can monitor and reevaluate the situation re. possible resection. But there is have to be the wash out period off this drug before of the surgery I guess, Bonni can tell more specific time frame when it can be safely done after off drug time, they have the experience doing that.

Dear Lucio,
It is so good to hear from you, and it was so thoughtful of you to provide such a very detailed and informative list and description of your Cediranib side effects. I am so very happy and grateful that you are having continued stabilization of your disease with no new mets, and that you have had shrinkage of your lung mets, especially the largest and most concerning one which has had a significant more than 50% shrinkage and is now no longer pressing against your heart, aorta, and bronchi. Although apparently the most significant tumor shrinkage has occurred early in the Cediranib treatment of most of the Clinical Trial patients thus far, Brittany did not begin to experience tumor shrinkage until a few months into the treatment, and since then she has thankfully continued to have significant shrinkage and even total disappearance of some mets. I think that each individual responds differently to the treatment. Personally I feel that as long as you are having continued stable disease with no new mets and no increased growth of your existing one, and as long as you are able to tolerate the side effects, that you should remain on the treatment. Certainly resection or ablation of your small met might be something which you should consider and discuss with your oncologist and surgeon, but if you do that, it might jeopordize your being able to continue on the Cediranib treatment unless the pharmaceutical company will allow you to temporarily discontinue your treatment for the necessary time required prior to, during, and following your procedure. This is a possibility as Brittany was allowed to do it when she had her superficial abdominal met removed, and also Jordanne did it when she underwent surgical repair of her jaw plate. The main issue is the amount of time required as I believe Jordanne was told the maximum time that she could be off of the treatment for surgery and recovery was a month. In Brittany's case, she was required to be off of the medication for two weeks prior to her surgery, and then resumed taking it about five days later when her incision was adequately healed. One of the concerns in discontinuing the medication for too long is the risk of rebound and possible rapid progression of the disease, so this is definitely something which you need to consider and discuss with the Clinical Trial oncologist. I am sorry that you are experiencing so many side effects from the medication which seem to be increasing in severity. Brittany also suffers many of the side effects which you described with the exception of the elevated Bilirubin levels and liver enzymes, the red blood cells in her urine, the chills and hot flashes, and the migraine headaches. It does seem that she is the only patient on this Board that has had the severe vomiting episodes although her Clinical Trial oncologist in Edmonton has told us that his other Cediranib treatment patients with different kinds of cancer than ASPS have experienced the same kind of periodic severe vomiting problem. Brittany has the same kind of "chemo brain" side effect that you describe which sometimes makes it difficult for her to concentrate and remember things, and to be, as you describe it, "just not that with it anymore". We have discussed with Dr. Sawyer the possibility of reducing Brittany's dosage to 20 mg. to try to reduce some of the debilitating side effects, and although Dr. Sawyer feels that this would be alright based on Brittany's lower weight, Brittany is not willing to take a smaller dosage at this time because she is concerned that the lower dosage might reduce the effectiveness of the medication. Hopefully one of the outcomes of the Clinical Trial will be to determine the optimum Cediranib dosage which will provide the optimum treatment results. In the meantime, it seems to be an individual matter based on the individual patient's side effects, their toleration of the medication, and their response to their dosage. I Hope that your side effects will stabilize and become more tolerable, and that your next scans will show continued stable disease and tumor shrinkage. I will be anxiously awaiting your next update and the outcome of your consultation with Dr. Lee regarding resection of your most concerning lung met. In the meantime, please take care Lucio and know how deeply appreciated your thoughtful update and very informative discussion of your Cedrianib side effects is.
With special caring thoughts, healing wishes, and continued Hope,
Bonni

Thanks for all your details, Lucio. It really helps when considering all these different medications.

I just wanted to add a little of what we've learned recently re: ablation.

If that one close in shrinks a little more, it may even be a safer one to ablate. You don't want it to have any contact near pulmonary vessels.

Rolle told us that he was concerned if he did a redo on 'K' on the left that it might put her at risk of lobectomy too. That is why he suggested ablation. All the rest of hers are small. Ablations are much easier than thoracotomies. Usually there is 1-2 days of hospitalization and home as long as there's no pneumothorax. No chest tubes. Liver ablations are come-and-go (no overnight).

Our RFA guy at Seattle Childrens said he could do hers, but we learned he cancelled his phase II trial after a child died - apparently the tumor was wedged up against the pulmonary vessels - but this guy also has more experience with liver than lung. We would prefer cryoablation with Littrup (Brittaney had in 2004) - also he published a report on an ASPS patient earlier than this who was treated with cryoablation.

Be careful if you stop the Cediranib. It might be helpful to know you've got the latest opinions re: the best time to do surgeries or an ablation. Most surgeons usually require 3-6 weeks off medications to do surgery, but there's been some data to suggest that aggressive re-vascularization occurs as early as 7 days post-stopping the med. It would be good to ask surgeons who now have experience with surgeries after anti-angiogenesis inhibitors.

Thank you all for your promp replies. You've all given me a lot of things to think about and some good questions to ask my protocol folks, susgeons and oncologis. I'm still on 30 mg and I'm still wrestling with the idea of lowing my dose. I'll be at the NIH on monday and hopfully they can address some of my concerns. I'll update when I get some more info or if something changes.


thanks again

Dear Lucio,
I agree with 'F' that ablation may be a better alternative to resection of your most concerning lung met since there is a greater risk of bleeding and a much longer recovery time with a thoracotomy which would require you to be off of the Cediranib for a more extended period of time, increasing your risk of rebound or jeopordizing your continued participation in the Cediranib Clinical Trial. Both of Brittany's Cryoablation procedures were done as out patient procedures with only a few hours of post-op recovery in the recovery room and no hospitalization. She was hospitalized for several days with her RFA procedure due to a pneumothorax during surgery, and again several days later due to a post-op pneumothorax. Both lung Cryo and lung RFA require a few days of post-op recovery, rest, and limited activity, and you cannot fly for a week due to the risk of pneumothorax in the event the plane experiences a rapid loss of altitude. With Cryo Brittany was given only sedation medication as Dr. Littrup wanted her to be awake so that he could have her hold her breath as needed, but with RFA she was given a general anesthetic and was not awake for the procedure. I encourage you to discuss ablation as a possible treatment option with both Dr. Lee and Dr. Spinoza when you next meet with them. I will be anxiously waiting for your next update regarding your treatment decision. Take care and travel safe to Bethesda.
With special caring thoughts, healing wishes, and continued Hope,
Bonni

Lucio,
Jordanne was off the the drug for 4 weeks when she had her jaw surgery. Depending on who read her reports she may have had some slight increase in the size of her lung mets, that's how Dr. Kumar read it. But in reading the reports, the other person who read the scans said there was no change. I think that the Dr in charge of the protocol has some flexibility but probably 1 month is about max to go off. So far Jordanne seems to be having less problems with side affects since going off and coming back on the drug. We have made some changes to her diet which may have helped as well.
She'll be at NIH on Monday so if you see a beautiful skinny blonde in a wheelchair or with crutches be sure to say Hi.
Bestwishes for your next visit and that you will be given wisdom and discernment to make the right choices for your health.
Dotty

Hi Hi,
a lot happened and we haven't had a chance to write about it (read: we were kinda lazy but we have been following along with how everyone else is doing). Lucio had to stop Cediranib back in mid-June, the side effects were becoming unmanageable. the recommendations from various doctors we have seen since was: scans again 2-3 months. steadily gaining weight and feeling better, and last week was the chest CT and brain MRI. today, results received.
not good news. he gained back the losses and then some. the most concerning met is pressing close to his aorta and it went from 1.4x1.1cm (12/2008) - 1.3x0.8cm (cediranib) - 1.9x1.5cm (today). one other met also increased ~33%, the others are possibly stable.
primary oncologist wants him to talk to a cyberknife guy and a cardiothoracic surgeon. she wrote him a script for Sutent, and attached an article on 2 out 4 ASPS patients showing a partial response on 37.5mg daily, and one had stable disease (article was to support prescription for sutent for insurance). we are all just waiting for the rejection. any ideas for the appeal letter?
waiting to talk to talk to dr. lee (UCLA) about surgery, but last time we were there there was a big question of a possible lobectomy, which is why we decided to try cediranib first. city of hope (duarte) might have a pazopanib trial coming up (if it's not there already?), but it's possible lucio is not eligible due to his previous drug treatments. and since r1507 was a dud, it appears he might be ineligible for similar igf pathway trials. stuck in southern california, we're both underpaid engineers so him travelling for cryoablation or to see dr. rolle could be complicated. any thoughts or insights?

Other options: the one our daughter is on - PF02341066 or Crizotinib, also Afinitor was helpful in the German abstracts that were posted. We were also able to get Afinitor through Blue Cross. Other agents - that ALB drug that was in Boston.

Crizotinib was hard the first month, but now it's easy...and that seems to be the trend.

If you'd like to talk tomorrow by phone, I'd be happy to share what I know. Also you could have the slides at UCLA sent for molecular profiling. It might help you make a decision re: which trial drugs to pursue. Also sometimes if your tumor has the target and you don't qualify or some other situation, you still might be able to get in.

BTW, have you read Anticancer? Diet and exercise may be helpful too in addition to trials drugs.