Saturday, April 9, 2016

Peptide Receptor Radionuclide Therapy (PRRT) Clinical Trial at Memorial Sloan Kettering

It’s been a long time since my last post.  I have been doing a lot of procedures for the PRRT clinical trial that I am a participant in at Sloan Kettering (MSKCC). 

I was lucky enough to get into this clinical trial because my doctor, Dr. Chan at Dana Farber, called Dr. Reidy-Lagunes at MSKCC to see if there was space available  for me if I met the qualification criteria. I was happy that they could cooperate with each other even though they work at competing institutions – sometimes politics can interfere with the best interests of patients.

This clinical trial is testing the use of a new peptide (DOTA-JR11).  The goal of the trial is that in patients with positive somatostatin receptors, the DOTA-JR11 will bind to the tumors and the attached radiation Lutetium-177 (Lu-177) can kill the cancer cells. 

The clinical trial has been extremely scan intensive and I had the following two scans before even entering the trial:

  • CT scan of the chest, abdomen & pelvis
  • Octreoscan
Diagnostic Phase

Once in the trial, I had the following scans, and this was just in the diagnostic, not the treatment part of the trial:

  • Glomerular Filtration Rate (GFR) - Scan to measure kidney function
  • 68-Ga PET scan with 68-Ga-DOTA-JR11 - Scan to measure if my tumors have the right receptors to bind to DOTA-JR11
These 4 scans were all done within less than a week.  My insurance company (Aetna) routinely denies most of my scans and they did so with the GFR scan.  Dr. Reidy had to call their affiliate company EviCore who acts as Aetna’s “bad cop” because they are the entity that denies most scans, to explain that it was a safety issue and then it was approved.  The good news is that I passed these scan diagnostics as well as the blood and other tests.  

Next phase of the trial:

Treatment Phase

The first step of the treatment phase consisted of dosimetry.  This procedure is a test of Lu-177 in the body to see how much radiation it delivers to the tumors and to your normal organs, primarily the kidneys.  The procedure is to give the patient IV amino acids to decrease the amount of Lu-177 that is absorbed by the kidneys.  Then an injection of a small dose (50 millicuries) of Lu-177 is given.  The IV amino acids are given for 3 hours.  Immediately after the IV is done, the patient gets a 20 minute PET scan that shows the distribution of the Lu-177 in the body; i.e., the kidneys, the tumors and other organs.  In addition, the same 20 minute scan is done at 24 hours, 4 days, and 8 days after the dosimetry.  There is also a SPECT/CT scan done at 24 hours to see a 3-D image of the distribution of Lu-177 in the body.  This series of scans is what the nuclear medicine doctors and medical physicist (never heard of that before!) looked at when they decided what dose of Lu-177 to give me when I did my first round of PRRT a few weeks later.

You can only imagine how all these scans got my insurance company (Aetna/EviCore) into a denial frenzy!  I got letters and robocalls from EviCore practically every day for the past month as they tried to deny my scans and then approve them after a call from the doctor.  What a crazy health system we operate in!  

The dosimetry left me quite fatigued and nauseous for about a week afterward. I felt like I had the flu.  Dr. Reidy gave me a prescription for Zophran, an anti-nausea medication to take 3 times a day as needed for up to 15 days.  Of course, my drug provider, Express Scripts has set up this drug so that I can only get 12 pills at a time, meaning that it takes 4 trips to Walgreen’s to get my 45 pills.  Nice way to treat a nauseous cancer patient!

I had the first round of PRRT a little over a week ago.  The procedure was exactly the same as the dosimetry except the dose of Lu-177 was 200 millicuries.  I’ve now finished all the scans and the flu/nausea symptoms are getting better.  I’ve managed to use the same 45 Zophran pills for both the dosimetry and PRRT so as not to spend so much time on line at Walgreen’s….I’m still getting letters every day from Aetna/EviCore asking my doctor for more information and denying the post-PRRT scans….

In between the rounds of PRRT, I will be getting blood tests done every 2 weeks.
This clinical trial allows for 2 rounds of PRRT.  I believe my next round will be in 10-14 weeks.  I will have a scan right before the next round to see if my tumors have shrunk, stayed stable or grown.  If they have grown, I will not be doing the next round as the PRRT would not have worked as expected. 

I’m hoping that that my tumors shrink and am looking forward to seeing what my next scan shows in a few months.  

Sunday, February 14, 2016

So Much for Tumor Stability

I am now off the Cabozantinib clinical trial. My latest MRI showed 11% growth in my tumors since the last scan on November 22nd.  Basically my tumors grew 22% in the 6 months I was on this clinical trial.  Not good! I have now decided that peptide radionuclide receptor therapy (PRRT) is my next treatment plan.This treatment is not FDA approved in the US, so the only current availability is:
  1. A clinical trial at Memorial Sloan Kettering Cancer Center (MSKCC)
  2. Going to Excel Diagnostics in Houston to do the PRRT under a “Right to Try” law.   
I could also go to Europe where several countries provide PRRT to neuroendocrine cancer patients. Given that I live in New York City, going to MSKCC would be the easiest option.  Also, my husband is having medical problems now as well and I am both patient and caregiver, a very difficult set of responsibilities.

I met with the MSKCC oncologist, Dr. Diane Reidy-Lagunes, on Wednesday to discuss the PRRT trial.  Her staff was concerned with my platelet levels because they were below 200 in January, which is the minimum allowed to be admitted this trial.  Since I have been off Cabozantinib for about 3 weeks, my labs have been improving and my platelets were fine.  I am now scheduled for several scans before the PRRT occurs. Since I have not been off Sandostatin for 6 weeks, I am scheduled for the scans later this month.

It felt strange to go back to MSKCC after leaving my first doctor there about 4 years ago.  Dr. Reidy and the clinical trial assistants were very nice and professional, unlike my prior experience.  I am looking forward to being in this trial.  I hope it shrinks and stabilizes my tumors for a while.  

Wednesday, November 25, 2015

Tumor Stability – Something To Be Thankful For

I just had my 4 month MRI in the phase II clinical trial of Cabozantinib, which I started in August.  My tumors are still stable, although they’ve grown by a small amount.  There were no new lesions or tumors found.  My doctor said the growth was small, measured in millimeters, and was probably in the range of 5%.  Under the RECIST criteria (described below), this counts as stable disease.  I will continue on this clinical trial until my tumors are no longer stable.  I am happy with this result and that my side effects from the drug are better now that I am on a lower dose.

I find the measurement criteria quite interesting.  Most people believe that stable disease means the tumors have not grown at all since the last MRI/CT scan.  In fact, these criteria say that the tumors can grow 20% from when the treatment started before being defined as progressive disease. This is assuming that there are no new tumors. 
Below is a description of how solid tumors are measured:
Response Evaluation Criteria In Solid Tumors (RECIST).*
·         Complete Response (CR): Disappearance of all target lesions
·         Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference point the baseline sum LD
·         Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started
·         Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
* Source:  Wikipedia

On this Thanksgiving I am thankful that my tumors are still stable and that things are status quo.  I hope you can find something to be thankful for and I wish everyone a Happy Thanksgiving.

Monday, October 5, 2015

Tumor Stability and Quality of Life Issues

In late July, I began a phase II clinical trial of a daily dose of 60 mg of Cabozantinib, also known as Cometriq.  This drug is administered once a day with three 20 mg pills.  As previously noted, this is an angiogenesis inhibitor that works to block the blood flow to the tumors.  The clinical trial requires that I have a scan, in my case both an MRI and chest  x-ray, after 2 cycles or 8 weeks. 

When I started the trial, I immediately was very fatigued and after a week or so, I was so exhausted, I could barely get off the couch.  It was difficult for me to breathe, not due to any pulmonary issues, but because I felt my muscles were too tired to inhale and exhale.  My doctor told me to stop taking the drug for 5 days and then to begin again at 40 mg per day (2 pills).  I did this and the exhaustion lessened a bit but then I began to have more problems with diarrhea and weight loss.  My liver enzymes were also elevated as a result of this drug.  My ALT was as high  as 115 (range 7-52) and AST was 105 (range 9-30).  Both were within the range prior to starting the trial.  After about a month on 40 mg, I began to get numbness in my fingertips (neuropathy), had a mouth sore and some red spots on my legs that looked like welts.  I also had pain on the bottom of my right foot that was attributed to the foot part of hand and foot syndrome.  Given this toxicity to the drug, my quality of life was suffering more than I was comfortable with, even if the drug was going to keep my tumors stable or shrinking.

Last week I had my 8 week MRI and chest x-ray and the tumors were stable!  This is great news!  Even better, we decided to lower the dose to 20 mg daily, hoping to stop some or all of these side effects.  I’m hoping to continue to be stable with the lower dose.  We’ll know how that works in another 8 weeks.

Saturday, August 8, 2015

Difficult Decisions

I haven’t posted in a while because I have been dealing with further tumor progression and decisions concerning my future treatment.  A previous MRI in March of this year showed tumor progression.  At that point, my doctor and I decided to increase my monthly Sandostatin LAR dose from 20 mg to 30 mg and run another MRI in July.  Unfortunately, the July MRI showed more tumor progression.  I needed to make a decision on my treatment plan fairly quickly. 

In my previous post, I described two clinical trials of angiogenesis inhibitors that are open and recruiting at Dana Farber (DFCI).  After reading the extensive clinical trial paperwork and discussing my questions with my doctor, I decided to try Cabozantinib.  This drug was approved by the FDA for thyroid cancer in 2012.  As I previously posted, this is a phase II clinical trial, meaning the drug is being tested in this case, for a different type of cancer (NETs) to see whether it works and what might be the best dose.  Cabozantinib is in a class of drugs called tyrosine kinase inhibitors (TKI’s).  I don’t have a huge understanding of the differences between the angiogenesis drugs.  My limited knowledge says that there are two types of drugs that are FDA approved and being used for NETs– TKI’s like or Sunitinib (Sutent) or mTOR inhibitors like Evorolimus (Afinitor).  The link below describes how these drugs work:

The way the clinical trial works is that I will be taking the drug (3 pills) once a day and being monitored by my doctors every two weeks (lab work and check-up). I’ll have an MRI after 8 weeks to see if there has been any change in my tumors. 

If my tumors stay stable or shrink, I’ll stay on Cabozantinib.  If they continue to progress, I’ll get out of this clinical trial and try something else.  I’m not sure if the “something else” will be Afinitor off label or another type of angiogenesis clinical trial.  I’ve been taking Cabozantinib for 2 days now and the only side effects I am feeling are fatigue and a weird metallic taste in my mouth.  The clinical trial consent form listed 125 possible side effects!   That was quite daunting.  So far so good, I hope it stays that way and works to stabilize or shrink my tumors.

Monday, May 25, 2015

Tumor Progression

It has finally happened to me - the dreaded news of cancer progression.  After 4+ years on Sandostatin LAR and debulking surgery my remaining tumors have started to grow and progress.  The good news is there are no new visible tumors. Things were stable until this March when my MRI showed tumor progression in my liver and one of my lymph nodes.  We increased my dose of Sandostatin LAR from 20 mg to 30 mg in March, hoping that might slow down any further progression.  My doctor wants to do another MRI in July to see if the tumors are still progressing.  In July, if the tumors are stable we’ll just continue with the 30 mg Sandostatin LAR. Since there are no approved drugs for mid-gut NET patients that have progressed on Sandostatin LAR, My doctor mentioned some clinical trials that I might be well suited for that are going on at Dana Farber as follows:

1)  Immunotherapy Phase 1B trial of MK-3475 in patients with advanced solid tumors

2)  Angiogenesis inhibitors (new form of chemotherapy) – there are a few choices for me in this category

The immunotherapy trial originally sounded interesting.  MK-3475 is the immunotherapy drug that has been used in advanced melanoma patients that has put some of them into remission.  It works by targeting a protein called PD-L1 that allows the cancer cells to live and multiply without disturbance from the immune system.  MK-3475 is a drug that blocks the PD-L1 protein so that your own immune system can attack the tumor.  Basically, if my tumor tested positive for PD-L1 then I would be eligible to try this clinical trial to see if the drug would work for my NETs. 

Unfortunately, my tumor test was not positive and from what I understand, none of the NET tumor samples tested positive.  I guess it means that this particular pathway to immunotherapy does not work for NETs and from what I’ve heard, most other gastrointestinal cancers.  So if the tumors progress further, it’s on to angiogenesis inhibitors for me.

Angiogenesis inhibitors have dissimilar side effects from most conventional chemotherapy medications because they work very differently. Rather than killing healthy cells along with cancer cells, as many chemotherapy drugs do, angiogenesis inhibitors only prevent new blood vessels from forming. 

At this point, there are no FDA approved angiogenesis inhibitors for mid-gut NETS.  For pancreatic NETs, Sunitinib (Sutent) and Everolmus (Afinitor) are approved.  The clinical trials that my doctor presented to me are for two drugs as follows:

1)  Cabozantinib:  This is a phase 2 trial of a drug that is approved for thyroid cancer. 

2)  Aflibercept:  This is also a phase 2 trial of a drug that is approved for colorectal cancer.  

Both these drugs, like all cancer drugs, have multiple side effects associated with them.  All things being equal (and I don’t know if they are), I’d take the Cabozantinib because it is available in pill form rather than infusion.  Neither of these clinical trials is randomized, meaning that there is no placebo arm so if I do one of them, I will definitely be getting the real drug.

My issue with angiogenesis inhibitors is that they seem to work better for pancreatic NETs than for mid-gut NETs.  My feeling is based on some articles I have read and the fact that they are only FDA approved for pancreatic NETs.  My doctor generally agrees with me but believes that the inhibitors may still work for mid-guts, just not as well as they do for pancreatic NETs.  

She also suggested taking Afinitor on an off label basis, meaning that it is not approved for my specific condition.  If I took Afinitor, at least I would not be subject to the rigorous rules of a clinical trial.  Novartis released information last week about a phase III trial called Radiant-4 that showed that Afinitor met the trial goals for gastrointestinal and lung NETs. This study might be enough for the FDA to approve Afinitor for other NET types than pancreatic.

I asked her if we should consider peptide receptor radionuclide therapy (PRRT). She said that this could be a possibility at a later stage.  She also doesn't think any liver specific treatment makes sense at this point since I have low liver involvement and tumors outside my liver. At this point my tumor load is light and I don’t have too much carcinoid syndrome. The angiogenesis inhibitors make sense to see if that helps slow progression. 

I went to a patient conference where Dr. O’Dorisio at the University of Iowa passed out a treatment chart that showed the different treatments available for NETs and their average time to progression (TTP).  If one looks at the treatment chart, the angiogenesis inhibitors have an average time to progression of 7 months.  That seems like a pretty short time to me but I know the TTP can be much longer for some patients.  My doctor thinks that there may be additional PRRT trials available in the US in the next year if necessary for my case.  It may make sense to partake in that treatment.  I could also go to Europe for PRRT where they are much farther along in the development of this therapy.  I have some time to think about this as I wait for my disease to progress.  Hopefully the progression will be slow.

The link to Dr. O’Dorisio’s chart is below:

Saturday, May 9, 2015


This week’s New Yorker magazine has another great article called “Overkill” by one of my favorite medical writers, Atul Gawande.  It’s about how new medical technologies and partnerships between doctors and health care systems have combined to produce excessive testing and scanning. These often render no value except to find abnormalities that do not need to be treated because they will never cause harm.  He goes into some potential solutions as well.  It is a comprehensive but enlightening article.  Enjoy!

Below are some excerpts as well as the link to the article. 

An avalanche of unnecessary medical care is harming patients physically and financially. What can we do about it?

Stuart Bradford in The New York Times
“Low value care is defined as one of twenty-six tests or treatments that scientific and professional organizations have consistently determined to have no benefit or to be outright harmful.  In just a single year, the researchers reported, twenty-five to forty-two per cent of Medicare patients received at least one of the twenty-six useless tests and treatments.

“The virtuous patient is up against long odds, however. One major problem is what economists call information asymmetry. In 1963, Kenneth Arrow, who went on to win the Nobel Prize in Economics, demonstrated the severe disadvantages that buyers have when they know less about a good than the seller does. His prime example was health care. Doctors generally know more about the value of a given medical treatment than patients, who have little ability to determine the quality of the advice they are getting. Doctors, therefore, are in a powerful position. We can recommend care of little or no value because it enhances our incomes, because it’s our habit, or because we genuinely but incorrectly believe in it, and patients will tend to follow our recommendations.”

“Overtesting has also created a new, unanticipated problem: overdiagnosis. This isn’t misdiagnosis—the erroneous diagnosis of a disease. This is the correct diagnosis of a disease that is never going to bother you in your lifetime.”

“H. Gilbert Welch, a Dartmouth Medical School professor, is an expert on overdiagnosis, and in his excellent new book, “Less Medicine, More Health,” he explains the phenomenon this way: 'we’ve assumed, he says, that cancers are all like rabbits that you want to catch before they escape the barnyard pen. But some are more like birds—the most aggressive cancers have already taken flight before you can discover them, which is why some people still die from cancer, despite early detection. And lots are more like turtles. They aren’t going anywhere. Removing them won’t make any difference'.”

“We’ve learned these lessons the hard way. Over the past two decades, we’ve tripled the number of thyroid cancers we detect and remove in the United States, but we haven’t reduced the death rate at all. In South Korea, widespread ultrasound screening has led to a fifteen-fold increase in detection of small thyroid cancers. Thyroid cancer is now the No. 1 cancer diagnosed and treated in that country. But, as Welch points out, the death rate hasn’t dropped one iota there, either. (Meanwhile, the number of people with permanent complications from thyroid surgery has skyrocketed.) It’s all over-diagnosis. We’re just catching turtles.”

“Every cancer has a different ratio of rabbits, turtles, and birds, which makes the story enormously complicated. A recent review concludes that, depending on the organ involved, anywhere from fifteen to seventy-five per cent of cancers found are indolent tumors—turtles—that have stopped growing or are growing too slowly to be life-threatening.”

“We now have a vast and costly health-care industry devoted to finding and responding to turtles. Our ever more sensitive technologies turn up more and more abnormalities—cancers, clogged arteries, damaged-looking knees and backs—that aren’t actually causing problems and never will. And then we doctors try to fix them, even though the result is often more harm than good.”