Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Hi

I've just consented to go on cediranib and have been reviewing the helpful posts about side effects. However, just wondering if people have managed to continue working whilst on the trial? I appreciate I may be on placebo at first and even if on trial drug the side effects are different for everyone.

I've just come off crizotinib which hasn't worked as lung mets still growing (and at a rate which means I am now eligible for cediranib). Apart from a few weeks off work I was able to continue working with crzotinib with the help of anti emetics.

I will probably start cediranib in June as I turn 30 in May and want to enjoy my birthday first.

Many thanks

Chloe

Dear Chloe,
Welcome to the Discussion Board. I am so sorry for your ASPS diagnosis and for your failed response to your Crizotinib treatment. Unfortunately, thus far Crizotinib does not seem to have been successful in providing sustained disease stability for any of the ASPS patients on this Board who I am personally aware of who underwent Crizotinib treatment. When were you diagnosed with ASPS, do you have other mets than those in your lungs, how many lung mets do you have, and what is their size range? These are all important considerations before you begin a systemic treatment like Cediranib because it is the belief of those of us with extensive ASPS knowledge based on our personal experience and research that systemic treatments like Cediranib should be reserved as a last option for patients with widely disseminated, innumerous, unresectable, or untreatable mets that cannot be successfully or safely resected, ablated, or treated with laser resection or radiosurgery. This was the case with our daughter Brittany who has now very thankfully had six years of sustained disease stability on her Cediranib Clinical Trial which you can read about in this Cediranib topic under her name. However, Brittany started the Cediranib Trial only after being diagnosed with an unresectable/untreatable met in the head of her pancreas. Prior to that time, Brittany had undergone 23 surgeries/ablations/radiosurgeries and two other clinical trials in an effort to reduce her body's tumor burden and stabilize the progression of her increasingly aggressive disease. The problem with beginning a systemic treatment like Cediranib if there are other viable treatment options available is that if the systemic treatment ultimately fails and disease progression continues and becomes aggressive, there may be no remaining treatment options. Based on Brittany's personal experience with Cediranib, the side effects can be quite debilitating and I think that it would be difficult to work, at least full time, but it would depend on what kind of job you have, and Brittany's situation is exacerbated by chronic severe spinal pain from her major spinal met surgery seven years ago. Also each patient may of course respond differently to the drug in terms of both side effects and the effectiveness of the Cediranib. Brittany courageously endures the chronic negative side effects of the Cediranib and remains as active as possible, although she has unfortunately not been able to work for the past ten years due to the challenges of this insidious disease. In terms of you wanting to postpone beginning the Cediranib Trial until after you celebrate your 30th birthday, if a systemic treatment is needed due to aggressive disease progression or unresectable/untreatable mets, I think that you need to priortize what is most important because you may experience rapid rebound following your failed Crizotonib treatment which will need to be addressed immediately, or there may be no more openings left in the Cediranib Trial if you delay starting the Trial just to be able to enjoy your birthday. You will need to decide if your birthday enjoyment is worth the risk of postponing treatment which could possibly save your Life. In the meantime, I Hope that you will post your information on the Personal Updates section of this Board, or in the Anonymous topic if you prefer, because shared information is truly one of our strongest weapons in fighting this extremely rare and very challenging disease. Take care Chloe, know that you are not alone in your battle, and keep in touch with the Board as you are able.
With special caring thoughts, healing wishes, and continued Hope,
Bonni Hess, mother of 33 year old Brittany diagnosed at age 19 in July 2001

Dear Bonni

Thank you very much for your detailed reply.

I was also diagnosed age 19 (next week will be exactly 10 years since my diagnosis). I had surgery to remove the primary on my right thigh, followed by 6 weeks of radiotherapy. In 2009 routine scans revealed multiple lung mets on both lungs. I was told at the time that as there were lots and they were on both lungs surgery was not an option, so I didn't pursue it further.

As I am asymptomatic from the lung mets I just stayed under follow up with no treatment until June 2014 when I started on crizizotinib. I was told on 1st April it hadn't worked and that I am now eligible for cediranib. They measure the biggest 3 and whilst 2 had grown just mm in 10 months, one has grown over 1cm. I think the biggest one is 3.6cm at its widest. I've been told lungs still functioning fine though. Apart from lungs I have a pea size met on my right breast. They are also keeping an eye on lymph between stomach and liver as that has shown something but as its under 1cm its just "suspicious" at this stage.

I appreciate your comments about delaying treatment until after my birthday but I wouldn't be able to start until 1 May anyway as need one month between trials. Also I will need to do all the pre assessments so that probably means I won't be delaying it much, if at all.

I will ask my consultant about surgery/ablation and if I do commence cediranib will of course post on here how I am doing. I am a lawyer so whilst my job is office based it can sometimes be quite stressful.

Best wishes to your daughter, its great to hear that she has had such a good response to cediranib, just a shame it comes at the price of debilitating side effects.

Many thanks once again

Chloe (UK)

Hi Chloe, welcome to the board. I am Olga, Ivan's mom and you can read his story in the Personal Updates forum. We live in Vancouver, Canada.
There is one issue you would need to work on BEFORE you start the trial. We have noticed that soft tissue mets are not that responsive to cediranib and other TKI drugs. In Brittany case she had a soft tissue met that was growing on cediranib despite all other mets being stable or decreasing. Since the trial she was on was phase 1 trial (that addresses dose finding and Pharmacokinetic versus efficacy that phase 2 and 3 address), she was allowed to have that refractory met surgically resected and stay on the trial. If she was on the phase 2 or 3 phase trial for the same drug, this growth would disqualify her from staying on the trial despite other mets responding favorably. Two mets that you have - breast and abdominal - could be your weak spot in this trial. I would try to get them resected/cryo ablated before you go into the trial. I know that in UK it is really hard to make any move unless it is in the approved path, but try to talk to them. They need few targeted mets to measure the trials result, and they most probably do not need the abdominal and breast ones as they are smaller than 10 mm. Probably Pf. Judson knows about Brittany's case if he has an access to all the cediranib trial proceedings world wide, ask him if he is yours dr - if they saw good response from the soft tissue mets during the trial. If they are not supportive, I would just have the ablation elsewhere like in Germany, by some leading cryoablation drs there. We had some people on cediranib trial that lost their place on a trial because of this different response to cediranib and inability to treat the progressing mets separately (locally) while on a trial.

Dear Chloe, Thank you for the additional shared information about your ASPS journey and your current disease situation. Your having survived 10 years since your diagnosis without more extensive metastatic spread and no other surgeries or treatment other than the initial resection of your primary and post op radiation to the primary tumor site is really quite remarkable given the usual more progressive nature of this disease. I strongly agree with Olga about the importance of addressing and resecting/ treating your small breast met and suspected abdominal lymph met PRIOR to beginning the Cediranib Trial for the important reasons that she gave as well as to reduce tumor burden as much as possible to try to enable the Cediranib to be more effective. Also, I am concerned about the naiive approach of your doctors regarding "just keeping an eye on" the one centimeter lesion on your lymph node because a one centimeter suspected ASPS met should be addressed and treated before it grows any larger in order to provide the best chance of a successful response to ablation if that is a treatment option. Additionally, it is critically important that your disease is being monitored with regular chest/abdominal/pelvic CT scans as well as an annual brain MRI and full.body bone scan if you are not already receiving those scans. Please take care Chloe and keep the Board updated on your treatment decisions and experience as you are able, and know that those of us on this Board are here to try to provide shared treatment information, input, encouragement, and support for you. With special caring thoughts, healing wishes, warm friendship, and continued Hope, Bonni

Thanks for the additional information you both gave. I put the questions to my consultant who has spoken with Prof Judson. He does not advocate surgery and said he doesn't know of any evidence that soft tissue mets respond differently to cediranib.

As regards to mets growing more aggressively when you no longer respond to or come of cediranib, he said that it varies from person to person and they think it is more based on the biology of the person's tumours rather than cediranib per se. Also he hasn't seen this much with ASPS, with it more common in renal cancers.

So in summary, Prof Judson agrees that I should start cediranib.

I will be starting in beginning of June so will update on here with my progress then.

Thanks all

Chloe

Hi Chloe
My name is Debbie and my son is Joshua.
We've been fighting ASPS since August of 2012. Certainly not as long as you have.
Josh was 32 when dx.
I'd like to agree with Olga and Bonni on your possible breast tumor and any other soft tissue removal as in the following write up by Dr Kummar in the ced/ sutent trial ,here in the U.S, there were documented tumor reactions , if you will , of chest wall tumors I believe in which patients had to get additional pain meds to allievate the pain being caused by the Ced
This trial was of course a dose study as I understand it.


I respectively disagree with any doctor that says surgery is not an option as with almost EVERY article you will read will state , surgery is the best procedure whenever possible .
I bet the procedure could be performed at a minimum of 2 days?

http://www.ncbi.nlm.nih.gov/m/pubmed/23630200/--in the full text

Safety

The most frequent grade 2 or 3 adverse events were hypertension, diarrhea, transaminitis, proteinuria, hypothyroidism, and tumor pain (Table 2). There were no cediranib-related grade 4 or 5 toxicities. One patient discontinued treatment, despite experiencing a PR, because of chronic grade 1 to 2 GI symptoms. Dose reduction was necessary with continued treatment in 17 (40%) of 43 patients as a result of transaminitis, weight loss, hypertension, and proteinuria. The median number of cycles administered at full doses was two (range, zero to 11 cycles), with 14 (33%) of 43 patients requiring one dose reduction to 20 mg and three (7%) of 43 patients requiring two dose reductions to 15 mg daily. Eight patients developed grade 2 or 3 tumor pain associated with erythema and tenderness at the tumor site. This was observed only in patients with disease in peripheral sites, such as the extremities or chest wall. Exacerbation in tumor pain was typically observed 8 to 14 days after the initiation of study treatment, required increased doses of narcotics, and lasted 48 to 72 hours with relief of pain to baseline or lower levels. Patient 2, who developed grade 3 tumor pain and required narcotics and intravenous steroids for pain control, also developed mental confusion. Evaluation for reversible posterior leukoencephalopathy, including brain MRI, was negative. Mental status changes resolved with reduction in narcotics after improvement in pain symptoms.

Also Chloe, in reference to resistance, Olga sited an article to Lisa from China when they were visiting about pazonib and possible rebound.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3778288/

Till next time
Love
Debbie

PS What dose of ced will you be taking?

Dear Chloe,
I of course understand and appreciate that you sought advice from Professor Judson on the advisability of having your breast met and suspected abdominal met resected prior to beginning your Cediranib Trial, and while I am very familiar with Professor Judson and respectful of his knowledge and experience, I , like Debbie, must respectfully disagree with the advice and information which he has given you. We know from Brittany's personal experience that some soft tissue mets DO NOT respond to the Cediranib as was the case with her small superficial abdominal met which continued to grow while her remaining mets were stable or shrinking. As her extremely knowledgeable Clinical Trial oncologist said, " the abdominal met was not being a team player and needed to be removed". Once the abdominal met was resected in a short in office procedure, Brittany seemed to have a much more successful response to the Cediranib and experienced much more significant shrinkage and disappearance of her remaining innumerous and widely disseminated mets. I also know from personal networking with other ASPS patients who were being treated with Cediranib and discontinued it due to developed resistance and disease progression, that there can be/and have been incidents of aggressive rebound following discontinuation of the drug. During our almost 14 years of ASPS experience we have found that doctors do not always know everything about this extremely rare and poorly understood disease, and they can and do sometimes give erroneous advice. I know and acknowledge that I am not a doctor, but I also know that there have been several situations in Brittany's long ASPS battle in which we probably would have devastatingly lost Brittany if we had blindly accepted and followed the doctors' advice and not pro-actively sought a second opinion and/or based our treatment decision on our own personal aggressive research and extensive observations and networking with other ASPS patients. I personally disagreed with Professor Judson's treatment and care of a former English patient on this Board who tragically lost her very courageous battle earlier this year. I strongly encourage you to further research the issue and advisability of having your resectable mets removed prior to beginning your Cediranib treatment to try to reduce tumor burden and provide the best chance of a successful response to the Cediranib. I know that I have strong opinions, but they are based on almost fourteen years of hard earned anecdotal ASPS experience and constant and extensive observations, networking, and research. Whatever decision you make, please know that I share because I care so deeply about you and everyone in our ASPS Community dear Chloe, and that my intention and my Hope is that others can learn and benefit from both the positive and negative experiences and the successes and failures that we have had during Brittany's long ASPS journey.
With special caring thoughts, healing wishes, and continued Hope,
Bonni

Chloe, I have some comment here for you to figure out what is going on with difference in opinions - all the following is my personal opinion and does not represent the position of the organization Cure Alveolar Soft Part Sarcoma International.
I want to preclude the rest of my post by saying that Pf. Judson is the biggest ASPS expert and our hope for eradicating this disease, we value and respect him tremendously. But having said that - our goals are very much different. He is trying to eradicate ASPS disease via systemic treatment (in the future). We are trying to survive now and to give every one ASPS patient its best chance to prolong his life, using all the collective knowledge and treatment options existent now. He leads the cediranib trial and as the trial is not ended yet, the data is considered to be immature, so if he even knows about any heterogeneity in response between the differently located metastases, he will not assume it to be a fact - he needs to wait till the end of the trial, analyze the data and then he knows. Even if he has some suspicion, it is unscientific for him to assume.
We have no such constrains. If we see some trend, we just say it and try to overcame the limitations right now, giving the every patient the better chance to go trough the clinical trial with the maximization of its benefits. Intratumor heterogeneity and the mixed responses phenomenon is already described situation in other tumors responses to TKI like here:
http://www.ncbi.nlm.nih.gov/pubmed/25806267
Intratumor heterogeneity means that primary tumor and its metastases genetic make up are different depends on location (micro-environment influence) and time (continuous mutation influence). We have observed this mixed response more than once in our group. If the oncologists do not have enough statistical information to confirm it with confidence, it is just their side of the story. ASPS is a very rare disease and stats are not going to be available outside of the big clinical trials.
Pf. Judson is also a head of sarcoma oncology treatment guidelines committee in the UK (I am not sure re. exact name of the body). We disagree on the applicability of the common sarcoma guidelines to ASPS, it is a very slow growing sarcoma and we feel that it warrants more aggressive local treatments - surgeries, ablations - as ASPS patient live longer to maximize the benefits. In UK the metastases are only treated when symptomatic, in US and here in Canada they usually treated before they got symptomatic at the smallest treatable size as this gives the best opportunity to treat the given metastasis completely. We have stage 4 (metastatic) ASPS patients with brain metastases here living their normal life after their mets were resected or radiosurgery fried, but we lost few ASPS patients in UK to brain metastases being left untreated as they were asymptomatic (as per their guidelines).

Dear Chloe,
Olga has stated and explained very well the information and opinion that I was trying to convey. I agree that Professor Judson is a highly valued, regarded, experienced, and dedicated ASPS research oncologist. When I said that I disagreed with his treatment and care of a previous patient on this Board (as well as her very negligent treatment by her primary oncologist), my disagreement and frustration was indeed based on the fact that the patient's brain and liver mets were not diagosed at the smallest most treatable size because they were not symptomatic, and once they became symptomatic and were finally diagnosed, they subsequently grew too large to successfully respond to any treatment, and she had rapid and widely disseminated disease progression after being abruptly taken off of the Cediranib Trial. As Olga said, Clinical Trials by their very nature have very different goals which are scientific and data analysis based, more clinical in approach and theory, long term, and do not usually focus on the immediate goal of the individual patient which is survival. It is important to weigh all of these considerations and opinions when making your treatment decisions and to be as pro-active and knowledgeable as possible in making the decisions so that you will have the best chance of a successful outcome.
With more special caring thoughts, healing wishes, and continued Hope,
Bonni

Hello again Chloe,
I just wanted to express some additional thoughts regarding your decision to not have your small breast met resected prior to beginning your Cediranib Clinical Trial. Based on my extensive ASPS experience and knowledge, it seems to just make sense to rid your body of as many resectable tumors as possible if they are easily surgically removable since at this time it is an unknown as to whether or not you will actually have a successful response to the Cediranib and if it will be effective in destroying all or any of your tumors, whereas surgery will definitively remove the tumor without you having to play the waiting game to see if the tumor is going to successfully respond to the Cediranib and eventually die, or risk the tumor not responding to the drug and continuing to grow. If your small breast met is resectable as I assume that it is, based on Brittany's resection of her small ASPS breast met several years ago, it is a fairly easy outpatient procedure and one that we were very happy that Brittany underwent to successfully remove the breast met at the smallest most treatable size. I absolutely don't understand why any doctor would advocate not pro-actively removing easily resectable tumors, and why any patient would want/decide to have tumors which can be easily removed remain in their body, especially when all of the currently available ASPS study data documents that the best way to currently try to manage and treat ASPS is with resection/ablation/radiosurgery of resectable/ablatable/treatable mets since there is unfortunately no proven permanent ASPS treatment or cure available at this time.
With special caring thoughts, healing wishes, and continued Hope,
Bonni

Thanks for your responses and apologies for delay in responding. I was a little overwhelmed with the responses initially so didn't know how to reply.

Anyway, since I've last posted there has been further disease progression and I am now symptomatic from the tumours in my lungs, with breathlessness and coughing. The cough is affecting my day to day life, can't hold a decent conversation or do too much as it brings on coughing fit. Sounds pathetic but it really is exhausting.

There was a slight delay in me commencing cediranib as I coughed up blood the week before I was due to start trial, so we had to wait 28 days from then before I could start as per trial protocol. I started on cediranib second week in June although was admitted to hospital 5 days later with chest infection, so was off trial for approx 7 days.

I've now been back on it (or placebo) for 2 weeks. Initially the side effects were mild but the past 5 days I've had stomach cramps and diarrhoea for a few hours each day (mostly at night) which seems to get worse each day. Also have mouth sensitivity. I'm trying to see the side effects as a positive that I am actually on trial drug rather than placebo.

I've read that people avoided dairy but wondered if any other foods should be avoided? Any recommendations on what to eat would be appreciated!

Next scan is Middle of August so I'm really trying to stay positive and hope the scan shows stability, or better still shrinkage.

Thanks

Chloe

Hi Chloe

It's good to hear from you as I know we all presented ALOT of information to you since you started your post
Does your trial allow you to stop and get the lung tumor treated ?
It sounds like it does as you had to address the coughing up of blood , which I am sure sorry you had to go through
We have to be our own advocates in this VERY RARE disease

As Olga posted back aways

"In UK the metastases are only treated when symptomatic, in US and here in Canada they usually treated before they got symptomatic at the smallest treatable size as this gives the best opportunity to treat the given metastasis completely. We have stage 4 (metastatic) ASPS patients with brain metastases here living their normal life after their mets were resected or radiosurgery fried, but we lost few ASPS patients in UK to brain metastases being left untreated as they were asymptomatic (as per their guidelines)."

Also Chloe Olga wrote this in Jens post about inhalers


What oral inhaler do you use? I've read that sometimes the higher steroids doze is needed and under-treatment can cause the fibrosis to develop, and also that there is inhaled angiotensin-converting-enzyme-inhibitor (captopril?) that can be used, and also that radiation pneumonitis can lead to the development of bacterial infections that need to be considered if the patient keeps coughing. You probably need to investigate it more.
Olga
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Sincerely
Debbie

Dear Chloe,
Just a very brief note for now as I am on the run, but wanted to tell you how very sorry I am for your disease progression since you last wrote, and for all of your debilitating symptomatic shortness of breath and coughing. I am grateful that you have now been able to start taking the Cediranib and I am so Hopeful that it will be successful in stabilizing the progression of your disease and shrinking/destroying your mets. Based on your symptoms of abdominal cramping and diarrhea and mouth sensitivity I think that you are definitely receiving the Cediranib instead of a placebo. Are you having any other side effects like nausea and vomiting, headaches, hand/foot syndrome, joint pain and weakness, etc? If so, I Hope that you are able to tolerate them well. If you are having nausea and vomiting, I strongly recommend that you make arrangements with your oncologist to have intravenous re-hydration every two weeks to prevent the dehydration that is caused by the diarrhea and vomiting. Prior to Brittany beginning her re-hydration regimen, she was having severe uncontrollable vomiting which required emergency hospitalization every 2-3 months, but thankfully she has not had an episode of this for the past couple of years since we scheduled the bi-monthly IV re-hydration. I agree with Debbie that if possible, it might be best to pursue and undergo Cryoablation for your largest and most concerning lung mets to try to reduce your body's tumor burden as much as possible and better enable the Cediranib to work. Regarding foods to eat/not eat, you should have received a list of prohibited foods from the Clinical Trial doctor, but the most important one to totally avoid is grapefruit juice which has an adverse effect on the effectiveness of the Cediranib. I must close for now, but please know that my very best wishes and greatest Hope are with you for a very successful and sustained response to your new Cediranib treatment.
With deepest caring, special hugs, healing wishes, and continued Hope,
Bonni