Adjuvant therapy or not?

Texas_wedge said:

Mike, if your doctor says

Mike, if your doctor says it's up to you, don't do it.  If your doctor says do it, ask him why and try to establish his motives.  There is no evidence that adjuvant therapy has any effect at all in heading off recurrence of RCC.  That could change in future but that seems unlikely unless entirely new treatments emerge that alter the present situation.  If you seem to be clear, why subject yourself to toxic substances which are not shown to do you any good at all?

I second everything Tex is suggesting here Mike.

Save your powder for when you might actually need it.

todd121 said:

Adjuvant Therapy

Now I'll point out we had this discussion a few weeks back and you might want to search out not only that thread, but a few other times this has been discussed. There are some of us doing it and some not.

My tumor was T3a and I was told by 3 different oncologists (including 2 who are RCC experts, including Dr. Figlin of Cedars Sinai) that I have a 50% chance of recurrence. My uncle, an oncologist, encouraged me to do something to try and reduce my chances of recurrence. When I thought my tumor was a stage 1, I was very much unsure what to do but leaning towards perhaps not doing an adjuvant study. But when I got my path back and it was T3a, and I saw the other oncologists who said the chances were 50%, I changed my mind. (My first oncologist told me the chances were like 13%, but I firmly believe he was absolutely wrong. He used an automated model on Sloan-Kettering's website to calculate this.)

The goal of adjuvant therapy is to try and kill all the cancer cells in the body while there are realtively few(er) of them- before they get established. Once tumor(s) start to grow, there are so many cells that it's harder to fight them.

The study my oncologist looked at when he told me my chance of recurrence was in the 40-50% range was based on data from UCLA. I sort of recall that the T2 was in the 25-30% range, but you should double check this (and from my experience, I would suggest asking 2 independent oncologists). I saw studies that said recurrence is related independently both to the size of the tumor and the grade of the tumor. I believe your tumor size excludes you from Stage 1. I may be wrong, but I think tumors over 7 cm are grade 2. You need to see both the stage and the grade. I was stage 3a grade 3. The higher the grade, the higher probability of recurrence also. (I don't think tumor size and grade are completely independent, but I did see a study that showed that higher grade tumors had higher recurrence levels, independent of tumor size.)

I decided to do it for several reasons. First, it "may" reduce my chance of recurrence or delay the recurrence. I'm taking a drug that has been somewhat effective against tumors, so there is a possibility it will work for me. Second, I'm getting followed more closely than I would have otherwise. I'm getting scans every 18 weeks and blood tests every 6 weeks (the non-study care would have been scans every 6 months). Third, I'm getting very familiar with a great RCC specialist at a great hospital in case I need that later. (My previous hospital had no specialty in metastatic kidney cancer). Finally, I'm contributing to science and helping advance our arsenal of drugs. Somebody has to do these studies for us to figure out which drug will work in an adjuvant setting. I happen to be in a 50/50 double-blind study, so the odds are 50% that I wouldn't be taking a toxic drug anyway, but still get followed more closely.

My doctor encouraged me to do the trial. He thought the side effects are manageable and the toxicities are much less than conventional chemos for other cancers.

This was my thinking in deciding whether to do it or not. There's a second issue of deciding which drug trial to do, if more than one is available. That was a much harder decision for me because I got conflicting advice from the 2 RCC experts.

Todd

Todd,

As you point out, some are doing it, others are not.

I salute your willingness to be involved in any clinical trial that may benefit others in the long run.

To date no adjuvant therapy has been shown to be effective though.  That does not mean that you may not be part of a study that finally refutes that.

However, I do want to clear up a misconception. If you are taking a TKI they do NOT "kill" any cancer cells.  At least not directly.  They simply interfere with the process of angiongenesis (blood vessel growth).  By definition they are not effective "killing" micro-tumors because CTC's (circulating Tumor cells) have not clumped together and grown big enough to start the process of angiongenesis.  That happens after they are about 1 to 2mm in size.

todd121 said:

Agreed

Hi Neil,

And that's one of the reasons I didn't pick a TKI. I'm taking everolimus, an mTOR inhibitor.

I can't say I understand much of this biology. I was having a difficult time picking between a TKI and an mTOR inhibitor. I decided that I would take something that acts at the cellular level instead of at the systemic level (the TKIs). Now, because I don't understand the biology I can't say it's a very well educated decision. I would like to have learned more, but since I had one RCC specialist telling me a TKI was my best bet, and another telling me that the mTOR inhibitor was just as good a bet, and in the middle I had my uncle telling me that neither had experimental data supporting their opinion (hence why we need a study...) that I could pick either and feel like I did my best at making a decision.

I was thinking, here I have 3 oncologists with years of experience and training and they don't know which one will work better, and I have like 2-3 weeks to make my decision. Not really enough time for a biochemistry class!

My intuition was that this thing that acts at the cellular level might be more inclined to delay and possibly reduce recurrence, while the TKI may be more likely to only delay it (which I think agrees with your point), helped me decide to take everolimus.

The other reason I decided, was I had a doctor telling me that in his experience I was going to have less side effects and more manageable side effects and more likely to be able to stay on the drug an entire year than the TKI.

But really, it seemed like a coin toss, and I went with the doctor I liked that was closest to my home at a hospital I liked, with this other fluff above helping me to feel good about my decision.

I'm pretty sure I'm on the real drug. I've been suffering with some bouts of nausea the past 2 days and have had some other side effects, but so far I can handle it. I'm giving myself permission to quit if things get too bad, so I have an "out".

This discussion has stirred me to go do some more reading on the long-term effects of everolimus. It's been used for several years in transplant patients. There should be some data available.

Todd

I'm glad you have the get-out card to play, Todd, and I wouldn't hesitate to use it as soon as I felt it appropriate.

My first thought is 'Rather you than me!'  However, you have identified some plus points.  The main one may be closer monitoring - you'll need it for all the side-effects of the drug but you'll have the comfort of knowing you're getter more frequent screening for any recurrence (I take it you couldn't get 3 monthly scans otherwise - is that correct?).   You'll also have made the contacts which may prove a boon (and I hope it wouldn't alienate your main man if you quit the trial).  

The other saving grace is that you have a 50:50 chance you'll get the placebo, with all the benefits (monitoring and contacts) and none of the cost.  In your position I'd be delighted if I got the placebo and ready to quit rapidly if the drug gave me nasty adverse events.  [However, if you quit the trial, I suppose you also give up the more frequent scans, etc?]

I think the other supposed benefits are illusory.  'Helping science' and future patients is the usual sales pitch to help pull in those with a good streak of altruism.  I think this is largely flummery.  The trial is a huge, multi-center one and may involve very large numbers of trial subjects.  Given that all of the evidence to date demonstrates zero effect of adjuvant therapy in preventing recurrence, I question the morality of exposing large numbers of people, who don't currently require treatment, to a very nasty chemical purely on spec that, in many, many years time it might show some effect in reducing the frequency of recurrence, contrary to all the present indications. 

You're being a guinea pig for an experiment in which you may take a drug that will certainly do you harm and for which there's no indication at all that it will do you any good as adjuvant therapy.   (We desperately need guinea pigs for good clinical trials and the most suitable subjects are those who are ill and need treatment, and all the more so if other treatments have failed, or stopped working, and they have nothing to lose in helping the search for a new cure.   But you're not in that situation.)  Consider, also, that there are many exciting new developments going on that will very likely render this trial an utter waste of resources as a complete irrelevancy, long before they even start the laborious process of pulling the data together and begin to analyse and try to make sense of it.  Publication of the results is likely to be very long after there's any real interest in them.

It seems to me that your three oncs are being disingenuous.  As your Uncle has pointed out, neither of the RCC experts has any experimental data to support them and I think the ideas I've expressed above show why I feel this trial is not such a good idea.  To expand on this last point, I'll pick up on a remark of yours.  You say

"The other reason I decided, was I had a doctor telling me that in his experience I was going to have less side effects and more manageable side effects and more likely to be able to stay on the drug an entire year than the TKI."

From what I've read of the trial protocol, it seems that the plan is for the subjects to keep getting the drug/placebo over a period of almost 5 years.  I wouldn't dream of entering a trial of a drug like everolimus with a view to being on it for 5 years (and probably for no good reason at all).  Also, unless he's thinking of other personal health problems you may have, I think, on the basis of all I've read, that he's deceiving you in suggesting everolimus will be more tolerable than a TKI - I'm certain that Votrient is likely to be far less unpleasant than everolimus.

You've announced your intention of boning up on everolimus and I would strongly encourage you to do so.  A fast starter would be:

http://chemocare.com/chemotherapy/drug-info/afinitor.aspx

and I suggest you give full consideration to what you're letting yourself in for by studying the sections on common side-effects, precautions you should take and self-care tips for handling the problems. 

You can also look at the prescribing info at

http://www.pharma.us.novartis.com/product/pi/pdf/afinitor.pdf

and you won't get far into it before seeing why I would be reluctant to take it.   [I might have the opportunity to take part in a nivolumab/everolimus trial.  If so, I'd rather wait for a nivolumab trial, or treatment, with no risk of exposure to everolimus.]

PS  Of course some of us are braver than others - My Wife, surrounded by fabrics,  just said, engagingly, "I can't quite decide on the design of the quilt I'm about to make"  to which I responded "Oh dear"  as I high-tailed it into the distance as fast as my legs would carry me!

NanoSecond said:

mTOR insight

Todd,

Here is an excellent overview of how mTOR's work, etc:

http://www.ncbi.nlm.nih.gov/pubmed/21763970

I have the entire text downloaded as a .pdf if you want to see it.

-N

I just thought I would mention that, when my Oncologist mentioned the possible option of adjuvant therapy, I mentioned that on the ACOR site and someone there pointed out that, if my RCC were to recur and I wanted to participate in a better trial for metastatic RCC, I might be excluded because of having taken the first drug.  At least that is how I remember it.

Kathy

foxhd said:

right Kathy

Same thing here. Had I participated in the votrient adjuvant therapy, I woud not have been eligible for the MDX-1106 trial that I am on now. There is no question that I am alive and well ONLY because of the MDX trial. I had identified eary that the adjuvant treatments had no vaue in my ongevity. It woud ony have heped in the research. I am much happier participating in my current research. Fox.

Soon after my surgery, my first Onc suggested a Votrient trial.  I had little info at that time, but I declined..  the Onc was absolutely puzzled why I said no...  I stated a couple of facts.. first we did not know I needed it, second we would not know if I got the real drug or not.  I did not have a clue that it could of taken me off any future trial list...  So you have now given me another good reason to have made my decision.   That said, had I known then what I know now, I may of given it more consideration than I did.  FYI, my first bottle of Votrient has arrived, soon that "fun" begins.

Ron - California

Texas_wedge said:

L-ish!

Fox - so gad you're sti doing we - but something seems to have knocked the L out of your keyboard!

What the "L" is the matter fox?  Break a finger?

UGH I WROTE SUCH A LONG RESPONSE HERE WHILE ON THE BUS YESTERDAY BEFORE MY PHONE WENT FLAT AND THE LOT WAS LOST. NOW THERE SEEMS TO BE A PROBLEMS WITH KEYBOARDS PATTERN... MINE IS STUCK ON CAPS. IN A NUTSHELL THOUGH, I WAS SUPPORTING ALL OF THE ABOVE POSTS, BUT ULTIMATELY NONE OF US CAN TELL YOU YES OR NO. YOU REALLY PUT IT BEST YOURSELF WHEN YOU SAID WHATEVER DECISION YOU MAKE IS THE BEST ONE YOU CAN AT THAT TIME.

I AM IN AN ADJUVANT STUDY. I RESEARCHED EXHAUSTIVELY (SO I THOUGHT). I ASKED MY DOCTORS ALL THE QUESTIONS I COULD POSSIBLY THINK OF, AND LIKE YOU I REACHED OUT HERE FOR GREATER EXPERIENCE AND ADVICE. SOMETHING THAT I DIDN'T  DO WAS GET A SECOND OPINION. WHILE VERY HAPPY WITH MY CURRENT MEDICAL TEAM, THERE ARE NO RCC SPECIALISTS WHERE I LIVE. FOR THAT REASON ALONE I BELIEVE THAT NOT ALL OF MY ANSWERS WHERE RESPONDED TO ACURATELY. IMPLICATIONS OF RESISTANCE AND EXCLUSION FROM HD-IL2 ARE BUT TWO OF THE MATTERS THAT I WAS ILL INFORMED ON  DESPITE THE WARNINGS OF OTHERS HERE AND MY ARMOURY OR RESEARCH PAPERS. THE POINT, GET A SECOND (OR THIRD) OPINION.

HAVING SAID THAT THOUGH AND NOW KNOWING THE MISTAKES I MADE COMING INTO THIS TRIAL, I WON'T MAKE THE SAME MISTAKES TWICE. AND THOUGH MY EXPERIENCE OF NEXAVAR HAS BEEN AT TIMES A LIVING HELL, I HAVE DECIDED TO STICK WITH THE STUDY. WHY? WELL AS HAS BEEN POINTED OUT SO MANY TIMES HERE, THERE IS NO SCIENTIFIC EVIDENCE TO SUPPORT ADJUVANT THERAPIES IN RCC. BUT, AND THIS IS MY BIG AND PERSONAL BUT, IF I CAN EVEN DELAY RECURRANCE IT MEANS THAT I CAN BE HERE WITH MY DAUGHTER IN THIS TIME AND SPACE THAT SCIENCE ALSO SAYS WE WILL NEVER BE IN AGAIN.  AND BESIDES, IF INDEED ADJUVANT NEXAVAR DOES TURN OUT TO BE A CROC, THEN WE CAN CROSS IT OFF THE LIST AND AVOID PUTTING OTHER SURVIVORS THROUGH THIS. 

CALL IT HOPE, FEAR, ALTRUISM,

Hanno said:

IT'S AN INDIVIDUAL DECISION...

UGH I WROTE SUCH A LONG RESPONSE HERE WHILE ON THE BUS YESTERDAY BEFORE MY PHONE WENT FLAT AND THE LOT WAS LOST. NOW THERE SEEMS TO BE A PROBLEMS WITH KEYBOARDS PATTERN... MINE IS STUCK ON CAPS. IN A NUTSHELL THOUGH, I WAS SUPPORTING ALL OF THE ABOVE POSTS, BUT ULTIMATELY NONE OF US CAN TELL YOU YES OR NO. YOU REALLY PUT IT BEST YOURSELF WHEN YOU SAID WHATEVER DECISION YOU MAKE IS THE BEST ONE YOU CAN AT THAT TIME.

I AM IN AN ADJUVANT STUDY. I RESEARCHED EXHAUSTIVELY (SO I THOUGHT). I ASKED MY DOCTORS ALL THE QUESTIONS I COULD POSSIBLY THINK OF, AND LIKE YOU I REACHED OUT HERE FOR GREATER EXPERIENCE AND ADVICE. SOMETHING THAT I DIDN'T  DO WAS GET A SECOND OPINION. WHILE VERY HAPPY WITH MY CURRENT MEDICAL TEAM, THERE ARE NO RCC SPECIALISTS WHERE I LIVE. FOR THAT REASON ALONE I BELIEVE THAT NOT ALL OF MY ANSWERS WHERE RESPONDED TO ACURATELY. IMPLICATIONS OF RESISTANCE AND EXCLUSION FROM HD-IL2 ARE BUT TWO OF THE MATTERS THAT I WAS ILL INFORMED ON  DESPITE THE WARNINGS OF OTHERS HERE AND MY ARMOURY OR RESEARCH PAPERS. THE POINT, GET A SECOND (OR THIRD) OPINION.

HAVING SAID THAT THOUGH AND NOW KNOWING THE MISTAKES I MADE COMING INTO THIS TRIAL, I WON'T MAKE THE SAME MISTAKES TWICE. AND THOUGH MY EXPERIENCE OF NEXAVAR HAS BEEN AT TIMES A LIVING HELL, I HAVE DECIDED TO STICK WITH THE STUDY. WHY? WELL AS HAS BEEN POINTED OUT SO MANY TIMES HERE, THERE IS NO SCIENTIFIC EVIDENCE TO SUPPORT ADJUVANT THERAPIES IN RCC. BUT, AND THIS IS MY BIG AND PERSONAL BUT, IF I CAN EVEN DELAY RECURRANCE IT MEANS THAT I CAN BE HERE WITH MY DAUGHTER IN THIS TIME AND SPACE THAT SCIENCE ALSO SAYS WE WILL NEVER BE IN AGAIN.  AND BESIDES, IF INDEED ADJUVANT NEXAVAR DOES TURN OUT TO BE A CROC, THEN WE CAN CROSS IT OFF THE LIST AND AVOID PUTTING OTHER SURVIVORS THROUGH THIS. 

CALL IT HOPE, FEAR, ALTRUISM,

I think we're losing sight of the goal of adjuvant therapy here in our discussion. The exact goal of it is, to take a drug that might not be effective in totally wiping out the cancer in the case of metastatic disease, where the total number of cancers cells is very large, and using that drug when the cancer cell load is very small, so that you keep the cancer from getting a foot hold and coming back. The issue is that when there are large numbers of cells, there's an increased probability of finding large numbers of cells that are immune to the drug. When you have a small number of cells to start with, the therapy drug kills off the majority, and you end up with a much smaller number (maybe 0) of cells remaining. If there are very small number of cells remaining, hopefully the immune system can handle those.

Hanno, you and I are in the situation where adjuvant therapy might be beneficial. Of course there are no drugs (so far) that have been proven in an adjuvant setting for RCC, but I don't think we should be discouraged from trying. Waiting and taking a chance might be ok with some, but I want to do what I can now for my situation to increase my chances. Even delaying recurrence would be good, like you said. These drugs we are taking have been shown to be somewhat effective in metastatic disease, so there is a decent chance it might help us. We know that these drugs don't seem to cure RCC when the tumor load is larger, but it might in our situations (NED because of surgery), where if there are cells, there are relatively few of them.

I think the argument of skipping one experimental therapy (that you aren't sure is going to work) to wait on another (that you aren't sure will work) because the first might keep you from the second, is a red herring. We have to make a decision on the situation in front of us on the treatments that are available for our situation. The treatment should be decided on it's merits. Of course there is unknown involved. We all have that for our situations, because there is no safe, effective cure for this disease.

I've been suffering some side effects this week, but nothing like what you guys on the sorafenib trial are suffering from. I was getting discouraged, though, Monday and Tuesday when my nausea spiked. It is tempting to stop taking the drug and not worry about the disease until/if it comes back, but I decided to stick it out. I looked at the data, and the drug I'm on has been effective in slowind down the cancer. That's what I want. Hopefully what we are doing will pay off.

Good luck to you.

Todd

NanoSecond said:

Control

Hi Todd,

As I pointed out earlier, there is no right or wrong answer to any of the thorny issues that we have to decide on regarding dealing with RCC.

I believe that each of us is seeking whatever modicum of "control" that we can over our individual fates.  But in doing so each one of us decides on an individual path that makes the most sense for them.

Some are content to listen to their doctors advice and to leave it at that.

Others strive to be more proactive.  I do that by trying to follow what I believe is the healthiest diet and nutrition possible.  Will this approach "cure" my cancer? No - not by itself.  But can it help fight this disease? I certainly hope so. And, at the very least, I feel otherwise healthy.  That's my particular way of getting some control over my situation. How much? Who knows? Who cares? This is just what I can do to change myself.  But does that mean it is "right"? The question makes no real sense in any broader context.

I salute what you are doing and I think you have made an excellent case for continuing on your path - regardless if it ultimately "works" or not.  Even if it doesn't - it is not a waste or a failure by any stretch.  Something incredibly valuable will be gained from your (and others) experience.  Just remember that our patron saint, Dr. Judah Folkman, was ridiculed for over 30 years for his ideas and before he finally succeeded.

So go forward and don't look back.

You're right. We are operating in the darkness here and doing the best we can.

BTW, Neil, could you send me that mTOR inhibitor explanation in PDF you mentioned? I sent an email to you but never got a response. Perhaps it ended up in your spam folder?

Todd