Category Archives: Your Role

by peggyrcc | January 21, 2013 · 10:08 pm

CT Scans Cost? a) $930, b) $8010 or c) $626? What’s the Difference?

Which is Better–A CT scan for $930 or $8010?

Is there a difference? How do I choose? Do I get fries with that?

I need CT scans of my chest, pelvis and abdomen, or at least I did. Eight years ago, I was diagnosed with Stage IV cancer, got healthy, but still need pre-emptive CT scans.

Metastases were all over my lungs, and the kidney dug out of my belly, so I get “CT scans of the chest, pelvis and abdomen, with and without contrast. Compare to previous scans.”

Consistency of scans is important, so I am scanned at the same place, prepped by the same nurses, and have reports from the same radiologists. Only billing is inconsistent.

My EOB showed three scans, three CPT codes, three “retail” prices, totaling $8010, and three insurance prices discounted by $6613. Good so far.

Insurance pays their portion, less some amount, giving the provider $770. I am billed the balance of $626, worth $1396 to the provider.

Before my next appointment, Medicare decided that pelvis and abdomen scans done simultaneously are one procedure. Unsure where the abdomen ends and pelvis begins, and where the kidney fits, and how low the lungs go, this made sense. It did not affect my scans nor my report.

As the three CPT codes became two, (72191 +74160= 74177) the beloved discounts didn’t accompany those codes. With the $1000 maximum daily payout by the insurance company, my $8010 scans were calculated to charge me $4074! Now the scan was worth $5074?

Not happy, and not about to pay, I asked the cash price of the scans. Just $930!

Calls to the insurance company, the third party whomever, the billing department and trips to the billing office, and subsequent calls to the state insurance office. And the letters to the collection company and the whining…

My best offers were “charitable assistance, paying the bill over two years”, and “just tell Medicare to change the codes back”. That I offered to pay my fair share and that I wasn’t a Medicare patient meant nothing. And have you ever “just told” Medicare anything?

Time for another scan: “I’ll take the cash triple CT”, and asked to be billed directly. The $930 scan was a bargain after the days spent fighting for my $626 scans.

Murphy’s Law applied, so my insurance was billed, not me. Thus, another $4074 bill to me. And the trips and calls started again.

What does the typical CT scan really cost, per the hospital’s published reports to the American Hospital Directory? My provider states a single “CT without Contrast” to be $198, but $60 at their satellite center. With contrast, the figures go to $283 and $89, respectively. Assuming I get three of the $283 scans, it costs $849—close to the cash price. Maybe I should get my scans from the satellite center at $89 x 3, for $267, really a deal!

No wonder there is such anger and distrust with the medical system, and not only with the insurance companies. The providers play the same game with the payer—whether the individual, Medicare or Medicaid, or an insurance company. The least empowered figure is naturally the individual, but in the long run, the anger and the cynicism generated drives a wedge between the patient and his individual providers.

The doctor who prescribes a CT scan and its cost has no idea—even the provider has no idea. And who is most vulnerable, and most likely to put off the scan? Me. And you.

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by peggyrcc | · 9:58 pm

Drug Interactions; Don’t Be Surprised!

At a City of Hope Medical Center, teaching hospital/research center, a pharmacist spoke to our patient group about drug interaction. She reminded us that we are responsible to follow the dosages, to alert our doctors to ALL the medications we take–prescribed and over the counter, herbals and supplements. “Remember that diet and its fat content affect our drug’s efficacy”, she added.

Pharmacists consider three types of interactions, which can happen between drug and another, with drugs and food or beverages, and drugs and conditions under which a drug is taken. They are described as follows:

1) Pharmokinectic issues of absorption, distribution, metabolic and excretion—how does the body bring it in, how long is it in the system, and where does it get absorbed? Does one drug slow down the effect, or prevent its use?

2) Pharmocodynamic effects occur when drugs with similar properties to one another are used together. They may interact with one another; such interactions might cause one or more to be ineffective, or too effective, or with side effects that are unexpected.

3) Toxicity may happen if the combinations of drugs have a toxic effect on an organ that would not occur with just one of the drugs.

For example, soranfenib (Nexavar) should be taken without food, while Sutent is recommended to be taken with food—but never with grapefruit juice.

Some drugs cannot be taken with NSAIDS; some are platelet inhibitors, for example. Sutent’s efficacy may be impaired by taking St. John’s wort, or when taken with barbiturates.

How do you keep track of all of this? Speak with the pharmacist whenever you have a change in medication—or right now, since you probably have not done that! Make an appointment to have the time cover all the questions. Bring in ALL the medications you use, even those you feel are “probably” safe or those you are embarrassed to admit you take! Pharmacists have access to extensive data bases, not only of the prescribed drugs, but also many of the supplements and herbals on the market.

As to herbals and supplements, she reminded the group that there are no controls as to the quality and quantity of active ingredients in the non-FDA approved supplements, and they can vary dramatically. Meningitis caused by a fungus in steroids produced by a US-company has caused the death of 44 and sickened at least 600 just last year.

It was fascinating to hear that, “Pharmacists don’t take medications”, but she emphasized that she rarely uses anything. It’s harder to convince her mother! Anticipating problems in the future with family-related conditions, she eats properly and exercises, for example.

Trust your gut about your body’s reactions. If something seems amiss, talk to your pharmacist or doctor to be sure you are not having a drug interaction.

Read the labels and follow the instructions. Not sure when and how much to take? Go back to the pharmacist or doctor for clear instructions.

Bring a “brown bag” of meds and such to your pharmacist to get a review of your meds. You know you should have already done this, so get going!

Remove the Beast, but What About Its Alien Babies?

When you have a tumor inside, which has hidden and grown and chewed away at your health for years, no sensible emotions are left in place, and no sense of patience is possible. All the advice to wait and see if it is really malignant, get a second opinion from a more experience doctor, just can’t wish/pray/eat/not eat it into oblivion, go to a really pretty spa in Mexico where they do wondrous things without a knife–they all sound alike.

I’ve always been healthy. Maybe I really am healthy and can live with this. Maybe the reason that I have been panting going up stairs, and having night sweats really mean more than menopause. Maybe they got the report wrong, but why did the ultrasound technician sudddenly go silent and begin to frown.

But reality does intrude, and at Mayo it was a reassuring reality, one which recognized that I was sick, that I needed TLC along with clinical expertise, needed to hear music from a beautiful piano, look at art and flowers, and needed Kleenexes on every table in every waiting room.

Coming in on an overnight flight, with a doctor friend having helped make the first appointment, I was anguished to realize that that I was in danger, and dependent upon people I did not know, and a system that was new to me. But the moment I picked up the phone at the Rochester Airport, I was connected to Mayo. Instantly the voice on the other end tracked my name, asked how I was, inquired if I had anything to eat or drink–so that she could schedule me for tests to be run on an empty stomach, and still find me time for lunch. When was the last time your medical system worried about you so tenderly?

I was brought directly to the intake area, where another person found all my records and my medical itinerary, with numerous pages of tests to be completed that day before my doctor’s appointment. With a pink marker, she circled the goals, including getting me fed, and with clear instructions, sent me to the first test. The atmosphere is serene but focused, with people from around the world, all ages and shapes, all coming to Mayo for help they could not get at home, or because Mayo had become home.

My prejudice, having been raised in North Dakota, is that the Midwest teaches people to value kindness and competence, all in abundance at Mayo. Although the nurse in the CT clinic had seen hundreds of patients in the weeks prior, and perhaps thousands over the years, her pats on the shoulder and gentle questions about my feelings comforted me. When she told me that she would include me in her prayers that evening, I knew she was sincere, and I was grateful.

My five o’clock appointment, now accompanied by my husband and sister, was both dreadful and calming. He reviewed the CTs we had brought from California, had all (!) the tests from earlier that day, and did a physical exam. When he pressed on my belly over the tumor, he could not help but ask, “Didn’t this guy feel this thing?”. The flash of anger was real, and the set of his mouth made me understand that this was obvious to anyone doing an exam. My several endoscopies and colonoscopies never included the checking my belly, the simple laying on of hands.

“This will have to come out, along with the kidney.” So much for the fancy “snip and bag it” approach which seemed so simple. By now I just wanted it out, without regard to scars and technique, and I had a second kidney. “This has to come out, and I can’t do it until Monday.” It was late Tuesday, but he understood the urgency in my gut. My kind of guy.

“Did your doctor tell you that you have mets in your lungs?” No, I had not been told. The stunning announcement of my life. I was not going to be able to get rid of the tumor and go on about my business! The mets in the lower lobes of the lungs were clearly visible in the CT scan from California. Were there 15-20 tiny snowflakes of tumor there? The new CT scan of the day showed a blizzard throughout my lungs. No way to operate on hundreds of mets, and life changed again.

“And we have to talk about followup. I will recommend high dose interleukin 2, which can be done here or at UCLA.” That was the lifeline which kept me being able to listen.To go from the need of an fairly non-invasive operation, to one which would open my gut and remove a kidney by slices of steel in my belly and then to a situation in which physical removal is possible! No wonder that people call having cancer a journey with no map.

There is only a goal, which is so simple. To get well. To not die too soon. To not die before my son graduates from high school, to not die before my daughter graduates from college, to not die and leave my children in the kind of pain which I had when my own mother died. We had a plan, with a drug I had never heard of, and one which had to work. I had no other option but to live.

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Filed under About Peggy, RCC Basics, Your Role

by peggyrcc | August 1, 2012 · 3:43 am

Systemic Targeted Therapy for metastatic RCC in 2012

Dr. Eric Jonasch of MD Anderson Cancer Center gave the following talk at a KCA patient conference in April 2012. “Systemic Targeted Therapies” include a group of drugs, all approved by the FDA in . the last six years. These drugs mark a critical breakthrough in providing more options for kidney cancer patients, and their use and complete integration into treatment is still ongoing.

(Where good slides were available, they were used; those which were hard to read have been recreated.)

I am going to talk as systemic targeted therapy for Metastatic Renal Cell Cancer, how we are using it, and the science about it, and how that leads us to new ideas, moving forward. When we talk about kidney cancer, we cannot talk about just one disease type. What I am going to talk about mainly is clear cell, and Dr. Tannir, my friend and colleague, is going to talk about the non-clear cell subtypes.

So what is ccRCC? It is essentially a cancer that looks like this under a microscope, and it was called this, back in the day. We more recently found that it has a mutation in the VHL gene (Von Hippel Lindau) in the vast majority of individuals with and I also run a clinic where I try to marry the information we have about hereditary kidney cancer with non-hereditary kidney cancer to improved therapies.

This is not to scale; it is 213 amino acids long and for the scientists in the audience, that is mercifully short, and it also has three exons in or three parts, or easier to study than most, but obviously still hard to study.

It essentially regulates how the cell reacts to oxygen. Obviously, oxygen is our life’s blood, we need oxygen, we need water, we need glucose. And our cells, if they feel like they need oxygen, they basically sit back and VHL will then take the transcription factor, which tells the cell which protein to generate, and then it breaks it down. If you have low oxygen state, then the cell will say, “Help, I need oxygen” and the VHL will step back, the transcription factors, HIF alpha and HIF beta are going to come together and you will get production of proteins, like VEGF which is a growth factor for blood vessels and some other things. If you have a mutation or something how an inactivation of the VHL gene, you have essentially an ongoing process of these cells, now cancerous, saying—somewhat untruthfully—we need more oxygen, we need more blood, build me an infrastructure.

That infrastructure is as follows: When we think of cancer we can’t think of cancer cells. The cancer cells are in black on slide and in blue are the stromal cells–the “glue” cells, and above those the endothelial cells or blood vessel cells. This triumvirate plus other cells generate an organ—and it really is an organ—that we call cancer. And when we use therapies, we are blocking specific areas there.

I’ll tell you a bit about the therapies we use now and that some of you are on, and what they are actually blocking.

Here is some terminology you are about to hear, some jargon, as we talk about trials.

Progression free survival (PFS)—time it takes for cancer to start growing again

Overall Survival (OS)—time it takes from start of treatment to passing of patients

So the “blood vessel starving” are the antiangiogentic therapies we currently have are listed here, and I am going to go through each of these in details.

Antiagiogentic Agents FDA Approved

1. Sunitinib (Sutent)

2. Pazopanib (Votrient)

3. Bevacizumab- IFN (Avastin + Interferon)

4. Sorafenib (Nexavar)

5. Axitinib (Inlyta)

mTOR Inhibitors Mammalian Target of Rapamyin Inhibitors

6. Temsirolimus (Torisel)

7. Everolimus (Afinitor)

We also have some up and coming drugs. And the way these drugs work with graphic shown again—is they block the blood vessels. They try to kill the blood vessels that feed the cancer. They don’t seem to have much effect on the cancer itself. That is why you have encountered resistance. That we can shrink this down, this cancer, but we can’t make it go away. And what we need, and on our wish list, are kidney cancer cell-killing therapies for the future.

mTOR Inhibitors

The mTOR inhibitors, of which there are two, Torisel and Afinitor ( Temsirolimus and Everolimus). What they do; they are actually working inside the cell perhaps both in the cancer cell and the blood vessel cell. And they are blocking particular proteins that seem to be up regulated, overexcited, that give them a selective growth advantage.

There we have on the bottom, kind of a brown color, mTOR, which if up regulated, results in production of and more survival advantage… for the cancer cells—which is shouldn’t have. What Torisel and Afinitor is block that signal.

So let’s talk about the drugs that in 2012 were currently using. The one that is probably most commonly used is Sutent or Sunitinib. It this is a pill and what is does the block those blood vessel cells. It doesn’t seem to block the cancer cells that much. It’s given officially 4 weeks on, 2 weeks off, although I don’t remember the last time I prescribed that way for anyone. I tend to start 2 weeks on, 1 week off as I find people tolerate it better that way, and its FDA-approved now since January of 2006, amazingly, a long time ago. But it is pretty amazing that we have some people who are still on it, starting in January of 2006.

The reason this drug was approved, it was compared to the old standard of Interferon. What we found saw was a prolongation of Progression Free survival, the time it took for the cancer to progress. And this was doubled to 11 months from five months, with Interferon, which some of you might remember as shot you give under the skin, three times a week. And the top line is where the individual were progressing, where they were on Sutent, and the lower line is where people were progressing on Interferon.

This is what is now call the Overall Survival curves, so essentially what we have here on the bottom is TIME, and the top lines the individuals that are still alive, and what we see on the top line are those on Sutent, and the lower line those on Interferon. It may not look like a huge gap, but what has happened on these research studies, when we do them, is what we call “cross-over”. When you progress on one of the drugs, you get to another and another and another. And the good news about this, it that it raises up the survival expectations to some degree, but it makes it hard to say, “That one drug is the one that is really making the difference.” Until we actually get therapies that consistently and reliably cure kidney cancer, we will still have this dilemma of having incremental benefits, but, “Hey, we’ll take them!”

Another drug which has come out and has been used since 2009 is Pazopanib or Votrient. It’s an oral drug, given daily, once a day. Same sort of thing, a blood vessel blocking agent.

This was tested in a slightly interesting as you have study where you had no therapy before, or you had immune therapy, and they were randomized, randomly allocated between the Votrient (Pazopanib) or placebo. I have to say that most of the people were enrolled in non-US sites because it is a little bit of a hard-sell for people, if you have not had any therapy before to be told we’re going to put you on placebo, maybe.

Nevertheless, the trial was accrued to and it demonstrated a very significant progression free survival, the time to progression of the disease for the individuals on the Votrient compared to those on the placebo. And what we see on the left hand side here, we see one of these showing the charts, with the orange line on top is the group (with Votrient, )people who remained free of progression over time, and the lower line, the people on placebo. And the progression free survival data for the people who had not been on prior therapy was as good as we had seen with Sutent.

We had a trial that is currently completed and is being analyzed to see if Sutent is better than Votrient, and we still don’t know which is “better”, but Votrient is certainly gaining traction because of the fact that it looks kind of promising.

Now its interesting when they did Overall Survival analysis, they did not succeed in showing a big difference, because as lot of people had gotten onto Votrient when they were on placebo at the beginning, and they got onto all sorts of other drugs.

So the next drug we are going to talk about is a little different (Avastin). What Avastin is –it’s an injectible antibody against the thing the cancer produces, the VEGF circulating in the circulation. It tries to take it out of circulation, so the blood vessel cells can’t see it. It’s given every two weeks, by injection, and officially given with interferon three times a week, so a little less attractive for some people.

This is a bit messy to read; the progression free survival in combination with interferon is substantially better than interferon alone, and this was done to two different studies and the data were true in both these big studies.

Thus we’re pretty confident, that along with Sutent, and Votrient, this prolongs progression free survival.

In terms of overall survival, 21 month for the interferon group, and next to it the interferon and Bevacizumab, 23 months. Again, in the same ball park as we were seeing with Votrient and Sutent, and not a statistically different figure. That statisticians take these numbers and crunch them and take p values and such, but still there was a lot of cross over data, and clearly, we are moving up the bar here.

One of my favorite data pieces is from the Sutent study. The patients on that Sutent study who had received Sutent or interferon were treated in countries where there was no opportunity for second line therapies or 3^rd. All they got was Sutent or interferon. And the people who were on the sutent arm only, and nothing else, had a 28 month survival, and the people who received interferon only, had a 14 month survival. So that’s an untarnished bit of data, showing the magnitude of benefit that they were receiving. That is more reflective of what we are seeing in our clinics today.

I wont’ go into this in detail, but bottom line is that. There’s a lot of number and you are probably getting numbered out. Bottom line we look at historical data compared to these people who are on these drugs and then get subsequent drugs, and we are seeing survival in the two to three to four years.Also known as Nexavar

The next drug we are going to discuss is Nexavar, which was approved in 2005, the first of these drugs to be approved. Same deal, the blood vessel starving drug, given twice a day, orally.

It was given initially to people who had not been given any targeted therapies before, but had progressed on immunotherapy and it demonstrated that there was an improvement in progression free survival again.

If you looked at Overall Survival there was improvement if you took out those people who crossed over. So again, modest improvements and definitely doing something for patients.

Now when this drug was compared directly to the untreated patient group to interferon, what was happening, was that it did not look like it was better than interferon alone. I just finished telling you that Sutent, Avastin, Votrient all beat interferon, and here we have a drug, that seemingly, didn’t. Subsequent studies were done which shows that PFS is somewhat better than this trial, but in reality in 2012, this drug is not much used in front-line therapy, for better or worse. It’s not that commonly used, and personally don’t use it much, based on these data.

What I have been talking about now, has been about individuals who have clear cell RCC, good risk features, and these are features looking at “are you anemic?, is your calcium elevated?, are you feeling and so on.” These are risk features to decide if a patient is in a good or intermediate risk category versus a not so good category.

And Torisel, an mTor inhibitor, which I talked about before, and was tested in this poorer risk population of patients, and was approved in 2007. Essentially, they took patients who had not had any prior therapies, and they checked off boxes. Do you have a low performance status?, your “good feelingness”, have you had your kidney removed before or not?, have you had anemia?, have you had high calcium?, have you had high LDH?, six categories in all. If you had at least three of those negative categories, they said, “OK, we’re going to put you on Torisel, and compare you with interferon and with Torisel and interferon in combinations.” And because they know this group of individuals tends to have a lower overall survival, they did an overall survival study.

It is a bit difficult to see in the background, but bottom line, that this was the first drug that showed in poor risk patients, that it improved overall survival, compared to interferon. Does that mean Torisel is good for people who have good risk features? Those who don’t have overall poor risk factors? Unfortunately, we don’t have an answer to that since that study has not been done. But this drug was approved, and we know that Torisel seems to provide benefit for patients with the poorest features.

SLIDE MAY BE MISSING

Does that mean that Torisel shouldn’t be used in a second line treatment where people have clear cell? No, it doesn’t. It simply means that those are the data that we have, and in the second, and third and fourth line setting—except for the data I am now going to present—we just have to figure out. “You’ve been on this, we’ve tried that, now let’s try this.” There’s a certain amount of art to it, as well as science.Also known as Afinitor

Afinitor was approved in 2009 for individual who had received either sutent, sorafenbit or both. This was a study that asked, “Have you progressed on Sutent or Nexavar?”

If yes, you were entered into the trial, randomized,ie the computer flipped a coin so that you went into the Afinitor or placebo, and we asked, “What was the progression free survival?”

This was clearly better in terms of progression free survival. And that’s why the drug was approved, and it is one of the most commonly used drugs in the second or third line for patients with metastatic kidney cancer.

The new kid on the block is Axitinib or Inlyta, in the second line setting. Dr. Brian Rini presented these data last year, looking at this, another blood-vessel starving drug. It’s the next generation, it’s more highly engineered to block more of the VEGF pathways, and it does less of the other stuff, which in some ways might be better, but you might want to have some “playing the field” in terms of stopping things in comparison of blocking one thing. So what did this data show?

This is the study. People had previously received one of these prior drugs, Sunitinib, Bevacizumab, interferon, Temsirolimus or Cytokine, and then they looked at the progression free survival.

The progression free survival was longer in the Inlyta(Axitinib) group compared to the Nexavar (Sorafenib), about 6.7 months versus 4.7 months.

What was interesting, was this was a group of individual who had receive either these targeted drugs before or immune therapy, and it shows it nicely in table form, but what it shows is that if you had received prior immune therapy, the Axitinib or Inlyta was way better than the Nexavar. If you had received prior targeted therapy, in the same class as Inlyta, then the differences were not that great. Then it’s better, the Nexavar is better in people previously treated with Sutent, for example, but its not incredibly better, but it’s a clean drug, and it’s very welcome addition to the drugs we have available. So we are using it and getting good results.

Up and comers. For the last few minutes we will show Tivozanib, another one of these blood vessel starving drugs. So we have 1,2,3,4,5, and now six of the same class, and like other classes of drugs, it is always good to have gradual improvement. It is in a pill form, same sort of thing, blocking VEGF pathways. There were some combinations, a phase III trial, showing that it does actually do better than Nexavar it was compared to, and is coming down the pipeline, probably an approved drug in the next year.

It is interesting that with all of these drugs, that the newer the drug, the lower the side effect profile as they are getting better and better at engineering these drugs, so at least we are getting a better drug in this class arena. But it is not dramatically better, and we need something better.

Combinations and Sequences

So what about combinations? In oncology, we like to do this, combine drugs. If you have drug A and that works and you have drug B and that works, then let’s combine it and hope we get a duplicative effect, and additive effect. Hasn’t really happened unfortunately.

Bottom line. Combinations at that time have not really consistently been shown to be superior to single agents. You get more side effects and you don’t get more bang for the buck in terms of survival or progression. Sequencing is really what we do, meaning you start with drug A and move to drug B, you move on to drug C. That’s what we do in the clinic. One of the trials that Dr. Tannir has championed is the START trial and we have 80-90 patients on this.

We re looking at, if you start with Nexavar or Votrient or Avastin, and you get randomized to one of the remaining drugs, does that provide you better benefit?

And there are other trials ongoing like that, the SWITCH trial, for example, going on in Europe, starting with Nexavar, then going to Sutent, or starting with Sutent and going on to Nexavar.

Or the RECORD 3 trial, with Afinitor followed by Sutent, or Sutent followed by Afinitor. We’re trying to figure out whether that works better for some patients than others.

This is a big table put up my former mentor Dr. Michael Atkins, a form thereof in 2006, and its been a gradually refined over the years. Bottom line is we have favorite drugs for untreated patients in the first line setting. We talked about immunotherapy before lunch, with Dr. McDermott talked about interleukin 2 and others, we have our blood vessel-starving drugs for that category as well. People with poor risk features, we have Torisel.

In the second line setting we now have good data from these trials that show that Afinitor and Axitinib probably provide benefit after failing these other drugs, and we have ongoing studies to try to determine whether or not one sequence is better than another. All this is nice, and we’re making real strides, but what do we really need to do?

Coming back to the picture of the cancer, we are good at hitting the red part, (the blood vessel structure), but why, when they get used, are we getting resistance after 10-12 months or so. Why can’t we kill the cancer cells?

We need new drugs that can block other receptors in those blood vessels cells. We need agents that can actually fix, look under the hood of the cancer cell, see what is misbehaving there, fiddle with it, and make it act more like a normal cell. If we can’t do that, kill the cancer cell. Agents that can actually block novel targets in the blood vessels, so we are looking at new receptors on there, and seeing if those drugs, in combinations with other drugs, can starve the blood vessels, are useful.

I am part of a nano-medicine grant, where the hypothesis is that, the big idea, is that a lot of the VHL proteins are mutated, are kind of wounded, but not dead. If we can revive them, maybe they can make the cancer cell behave more normally. One of the ways to do that, to raise the level of VHL, is with a drug called Carfilzomib to validate that.

MET Inhibitors

The last thing is those agents that can actually kill the cancer. This is amazingly, in 2012, still in the experimental stages. We have a colleague in Stanford, Imato Jatia(?) who has done some of these screens, some people at Harvard, all around the country, and we as well, looking at this strategy, where the cell kills itself. We have go to perhaps stop focusing as much as getting as yet another blood vessel-starving pill. An example of one of these drugs that might do this, is a MET inhibitor. So, a MET is another protein that is found on the surface of the Cancer cell. There were some reports at ASCO that this might a promising avenue.

So in summary, we are getting really good at blocking VEGF pathway, we’ve made real inroad in Overall Survival. MTOR inhibitors are doing a good job; we kind of know where to use these, but we are getting better at it. We have got to figure out why resistance occurs, and do something about it. Participation in clinical trials is key. We need to find drugs that kill the cancer cell directly.

QED

Systemic Targeted Therapy for metastatic RCC in 2012

Kidney Cancer Association National Patient Conference

Dr. Eric Jonasch; MD Anderson Cancer Center

April 14, 2012

Systemic Targeted Therapy for Metastatic Renal Cell Cancer in 2012

I am going to talk as systemic targeted therapy for Metastatic Renal Cell Cancer, what we are currently using and how we are using it, and the science about it, and how that leads us to new ideas, moving forward. Although I can see people here benefiting from what we do it is not enough.

When we talk about kidney cancer, we cannot talk about just one disease type. What I am going to talk about mainly is clear cell, and Dr. Tannir, my friend and colleague, is going to talk about the non-clear cell subtypes.

So what is ccRCC? It is essentially a cancer that looks like this under a microscope, and it was called this, back in the day. We more recently found that it has a mutation in the VHL gene (Von Hippel Lindau) in the large majority of individuals with and I also run a clinic where I try to marry the information we have about hereditary kidney cancer with non-hereditary kidney cancer to improved therapies.

Slide 2: This is not to scale; it is 213 amino acids long and for the scientists in the audience, that is mercifully short, and it also has three exons in or three parts, or easier to study than most, but obviously still hard to study.

Slide 3:

What it does, it essentially regulates how the cell reacts to oxygen. Obviously oxygen is our life’s blood, we need oxygen to, we need water, we need glucose. And our cells, if they feel like they hve enough need oxygen, they basically sit back and VHL will then take the transcription factor, it breaks it down If you have low oxygen state, then the cell will say, “Help, I need oxygen” and the VHL will step back, the transcription factors, HIF alpha and HIF beta are going to come together and you will get production of proteins, like VEGF which is a growth factor for blood vessels and some other things. If you have a mutation or something how an inactivation of the VHL gene, you have essentially this ongoing process of these cells, now cancerous, saying—somewhat untruthfully—we need more oxygen, we need more blood, build me an infrastructure.

Slide 4

That infrastructure is as follows: When we think of cancer we can’t think of cancer cells The cancer cells are in black on slide and in blue above, the stromal cells–the “glue” cells, and above those the endothelial cells or blood vessel cells. This triumvirate plus other cells generate an organ—and it really is an organ—that we call cancer. And when we use therapies, we are blocking specific areas there.

I’ll tell you a bit about the therapies we use now and that some of you are on, and what they are actually blocking.

Here is some terminology you are about to hear, some jargon, as we talk about trials and therapies. 1) Progression free survival (PFS)—time it takes for cancer to start growing again and 2) Overall Survival (OS)—time it takes from start of treatment to passing of patient

So the “blood vessel starving” are the five antiangiogentic therapies we currently have are listed here, and I am going to go through each of these in details.

We also have some up and coming drugs. And the way these drugs work (Slide 4 again) is by blocking the blood vessels. They try to kill the blood vessels that feed the cancer. They don’t seem to have much effect on the cancer itself. That is why you have experienced that we can shrink this down, but we can’t make it go away. And what we need, and on our wish list, are kidney cancer cell-killing therapies for the future.

mTOR FDA approved;

Temsirolimus (Torisel)

Everolimus (Afinitor)

The mTOR inhibitors, of which there are two, Torisel and Afinitor, Temsirolimus and Everolimus.

What they do; they are actually working inside the cell both perhaps in the cancer and blood vessel cell. And they are blocking particular proteins that seem to be up regulated, overexcited, in the cancer cell that give them a selective growth advantage.

There we have on the bottom, kind of a brown color, mTOR, which if it is overactivated, results in production of and more survival … for the cancer cells—which is shouldn’t have. What Torisel and Afinitor do is to block that signal.

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Filed under RCC Basics, Targeted Therapies, Your Role

by peggyrcc | June 19, 2012 · 5:06 am

Management of Toxicities Related to Systemic Targeted Therapy for mRCC- Hutson

Kidney Cancer Association National Patient Conference
Dr. Thomas Hutson, D.O.; Texas Oncology
April 14, 2012
Management of Toxicities Related to Systemic Therapy for Metastatic RCC

Summarized from transcript and video; edited for brevity; Many slides were text-only, so recreated to keep files sizes small. Slides recreated in bold lettering and this font to keep the files small.
To view the lecture, please follow this link; you may copy and paste it into your browser.
http://www.youtube.com/watch?v=KuJoHPA8sww&list=UUv0VRYOltlNQJLCyNMN61Nw&index=45&feature=plpp_video
Be aware that this is a personal summary of the lectures, and that I am not a medical professional; I am a patient, highly motivated to share the information from this KCA conference.

Dr. Hutson thanks the KCA for the conference and begins:
“The “Management of Toxicities Related to Systemic Therapy for Metastatic RCC” is the bane of our existence in RCC; Dr. Jonasch explained the drugs and their benefits earlier, but with benefits often come side effects.

About two-thirds of these side effects–the toxicities–are mild, and are managed by “supportive care”. This means using medications to ease the toxicities. About 1/3 of the toxicities are severe, and may require a dose modification, a dose holiday, stopping the medication for a few days. For most patients, when the medications are stopped, the side effects go away. Most are not permanent. But when toxicity becomes so severe that it affects quality of life, such that we have to withhold that medication, we may move onto another kind of therapy.

Early recognition is very important. I cannot predict if a patient will develop a toxicity and who will not. We think about that from the research perspective, look at it from a genetic perspective. Studies in the medical literature show that patients’ genetics can affect the patients’ toxicity to the drug. Those studies are called pharmacogenomics or pharmacogenetics–things that make an individual patient or a group of patients more susceptible to a toxicity.

These drugs are approved and used around the world and other populations have different toxicities than patients in the US. Asian populations have more severe hematological toxicities, lowering blood counts than we see in US or western European patients. Clearly there is something that is genetic, a so-called pharmogenomic abnormality. Continued research in that area will help us understand that and predict who is going to have those side effects, and let us choose drugs accordingly.

Early recognition of toxicities is the key to avoiding severe toxicities and avoiding dose reductions. When I start patients on these new therapies, I generally see them every 2-3 weeks for a few months. Thus, we can get a handle on side effects, and have a plan, and intervene as needed. Most side effects manifest in first couple of months of therapy, and are often chronic, ongoing. Once we identify them as potential problem for that patient, then we have a strategy. Then I see that patient less frequently, every 4-6 weeks.

I do encourage the doctors–the community oncologists—to do the same, give early aggressive management of the side effect. But the patient or caregiver needs to pick up the phone and call the doctor or doctor’s nurse early when you have a side effect.

We must also consider long-term effects from these side effects, because patients are living longer. With these agents, used in sequence, patients are living 3-5 times longer than they were just a few years ago. Some patients stay on them for years. One man in my practice has been on Sutent for eight years; there are side effects that he will live with for a long time. These therapies have only been available for 5-6 years, and we are just now learning how to utilize them and their toxicities.

Let’s start first with the VEGF inhibitors, and follow with the mTOR inhibitors. The VEGF inhibitors, include Avastin (bevacizumab), an antibody treatment given by IV, and the TKIs, oral drugs, Sutent (Sunitinib), Votrient (pazopanib), Nexavar (sorafenib) and Inlyta(Axitinib). Their similar toxicities are called class effects.

The effect we see in clinic and most often reported by patients is fatigue. Next are skin/hand foot sores, mouth sores, and diarrhea–daily monster diarrhea. Cardiac concerns, the biggest being hypertension; patients’ hemorrhagic effects don’t seem very big, but epitaxis, i.e., bloody nose is very common.

What is Hand/Foot syndrome? This is palmar plantar erthrodysesthesia, a medical term for painful palms and soles of the feet. Often with calluses form on the pressure points, even cracking. It can get very severe, so the patient is unable to use the hand or the foot, unable to walk. One of my patients had an acute reaction with Nexavar and within three days came to me in a wheelchair. Thankfully that kind of acute reaction is relatively rare. This type of skin toxicity manifests itself in the first 2-3 weeks of therapy, reaching a peak in the first couple of months of therapy.

How do doctors talk about this? You have all heard doctors saying, “grade 1 toxicity, grade 2 toxicity” What does that mean?

To standardize reporting, we use a common language—Common Toxicity Criteria—from the National Cancer Institute, and incorporated into clinical trials. Every doctor can grade the toxicity of a patient in the same way.

Grade 1 would be the mildest toxicity, an eruption, and macular/popular eruption, a bumpy patch. Grade 2 would be the eruption, the bumpy, and now itching, covering less than 50% of the body surface, and Grade 3 would be that eruption, with itching and covering greater than 50% of the body surface area.

For Grades 1 and 2 we use supportive care, and topical emollients and such. For the grade 3 toxicity, very severe, we might hold the drug, let the eruption go away, and potentially, lower the dose.” If it continued or returned, we might change the therapy. Same for Hand/foot Syndrome; Grade 1, minimal changes. Grade 2, more blistering, more peeling, more pain, but not really interfering with your daily activities. Grade 3 is means it interferes with daily activities; you can’t use your hands or feet, affecting your daily life. Same thing; grade 1 and 2, supportive care, and at grade 3, we would be more aggressive.

There is also actually a grade 4 toxicity, which is very extreme side effects and a grade 5, usually considered a side effect that resulted in death.

For supportive care we suggest Udderly Smooth, Bag Balm, Aveeno, non-allergenic emollients or creams; good skin hygiene, good foot hygiene, avoiding shoes with pressure points in them, pain medications, traditional pain medications. Some patients use Solarcaine spray, which numbs the surface of the skin.

The next side effect, mucositis or stomatitis, those are mouth sores. We can do a mix of things–tap water or salt & soda mouthwash, that baking soda kind of mouthwash, change toothpaste, as some brands burn.

Lidocaine, such as dentists use can numb the mouth. We don’t want the mucositis to affect the patient’s ability to maintain hydration, the ability to eat, so again, monitor it.

Grade 1; mild side effects–use all the supportive care. Grade 3, very symptomatic, can’t eat, can’t drink, very difficult, and we must consider holding the drug or lowering the dose.

With Hypothyroidism fatigue is the major issue and with some of our drugs, fatigue occurs in 55% -65% of patients.

Fatigue has many possible causes, as it not one thing that causes fatigue in any one individual. Patients can have multiple causes at the same time, including the disease itself, anemia, lowering of the blood count from treatment, and pain medications.

We found the association of these drugs with low thyroid early on at the Cleveland Clinic. Many of these TKIs, at some level or another can affect thyroid function. Doctors need check thyroid functions in patients, especially if they have fatigue. This is something we can easily fix and put a patient on thyroid replacement therapy. Levothyroxine, a thyroid replacement therapy, may be used by a 1/3 or more of patients. Thyroid problems induced by these drugs is very common.

With thyroid issues we are constantly chasing TSH. It fluctuates constantly with these agents. My patients’ TSH is going up and down on their synthroid doses, very common. The graph shown here with Sunitinib therapy, shows the fluctuations of the TSH. If there is problem I am unable to control, I bring in a specialist, an endocrinologist.

Next is dysphagia–difficulty in swallowing–and diarrhea, which is a big side effect, so will review diarrhea.

Grade 1 diarrhea is an increase of fewer than 4 stools over baseline, i.e., normal. In medical texts, it’s considered normal to have a bowel movement about every 36 hours. But if you are used to about 1 or 2 stools per day, and it goes up fewer than 4 more stools than what you normally have, that would be considered diarrhea. Diarrhea is NOT based on liquid stools, but the quantity of stools. So even if you were having formed stools, if you were stooling–having more stools—several times over your normal, that is diarrhea.

Grade 2 is when your stools increase more than 4-6 stools per day, incapacitating. Patients may become dehydrated, so we think about giving IV fluids. Grade 3 diarrhea is the very debilitating diarrhea. With the frequency of the stools, patients are becoming very dehydrated and may need lots of IV fluids, perhaps even hospitalization.

As to treatment, we try over the counter medications, Imodium or prescription meds like Lomotil, or different kinds of diets, the BRAT (bananas, rice, applesauce, toast and similar) diet, different foods. We get nutritionists and dieticians involved. We try to bulk up the food with fiber, with Questran (check with doctor), Fibercon, different fiber products, from over the counter. There are medications that the doctors can try, things like Octreotide or ?????, Sometimes we give pancreatic enzyme pills, that patients with pancreatic issues use. But most patients have grade 1 or 2; we’ll try to control it, not eliminate it. These patients will have diarrhea every day, but controlled with Imodium and Lomotil.

Hypertension is a classic side effect, almost an on-target effect of VEGF inhibition. It is currently being investigated to determine if hypertension can be seen as a biomarker of activity against the cancer. That may mean that patients who develop high blood pressure while in therapy may have a better chance of response to the therapy than those who do not.

We tell other doctors not to lower the dose of the cancer drug, as that is a good sign. Keep that going, but treat the high blood pressure. Do that with blood pressure drugs, the kind patients are already on.

If I have a patient who that is having difficulty, and we are using 2 or 3 blood pressure drugs, I will refer him to a nephrologist, a kidney specialist, who specializes in high blood pressures issues or a cardiologist to help me. But in general, it is very rare to find a patient who cannot be on these therapies due to blood pressure issues. If the patient is already on blood pressure medications, he is going to have troubles down the road. We identify that before starting the therapy, be proactive. Have the patient check their blood pressure daily, keep a diary, review that, have a plan so they can stay on their therapy.

Epitaxis–bloody nose seems to happen quite a bit, especially when seasons change. The listed medications don’t have direct effect on the mucosal lining, but may when patients have inflammation., if they don’t make the blood is more thin. We use bedside humidifiers, Vaseline in the nose, nasal steroids and different agents to try to control it. I’ve only had one or two patients who had a major problem.

If you are predisposed to hemorrhoids , there may be more bleeding than usual. Try the topical products here, like Preparation H. Gingival bleeding, bleeding from the gums when you brush your teeth. Key thing that will interest surgeons is wound complications. If you are to have a surgical procedure, tooth extraction, or a surgical procedure that normally considered minor, you have to be concerned there could have complications with bleeding. Sometimes we’ll have the patient hold the medication for a few days before a minor procedure.

With a major surgical procedure, the literature is very controversial about the length of time, generally a few days, but that is at the discretion of the surgeon, and their comfort level. You would resume the medication once there was appropriate wound healing. Usually the surgeon will visit with you a week or 10 days, and remove staples and that would be a good time to resume.

A lot of side effects and it sounds bad, but I share some hope here. Tolerance may develop with long-term use. This is information from Nexavar from the original trial. The first, HFSR, the hand/foot syndrome is shown with the axis as cycles, 1-5, a month of therapy. The high peak that patients seem to have in HDFS is in the first cycle and fewer as the weeks go by, they develop resistance. Same with the skin rash; same with diarrhea, hard in the first cycle, more controlled in the end. The fatigue is similar. So a tolerance can develop, but you have to fight through the side effects.

Now about the mTOR inhibitors. We have Torisel or temsorilimus, a IV weekly medication and Afinitor or everolimus, the oral medication. Just as with VEGF inhibitors, these have class effects associated with both.

We see fatigue, skin rash, but no hand/foot syndrome. It’s not that severe life/quality of life syndrome that we see with the VEGFs inhibitors. You can get a mucositis, less severe that the VEGF inhibitors or diarrhea, but that is essentially it. You do not get the high blood pressure issues as with the VEGF inhibitors. Generally patients feel that the mTOR inhibitors are more tolerable, less difficult, less severe side effects than the VEGF inhibitors.

Unique about this class are hyperglycemia–raising of the blood sugar and elevation of cholesterol. If you have diabetes while taking mTORs, you may have to adjust up your diabetes medications. If you don’t have diabetes, it can sometimes cause a drug-induced diabetes, that requires medication, and is reversible upon stopping the drug. It is reversible side effect, but we have to plan for it.

Hyperlipidemia–elevation of cholesterol levels. I will check cholesterol levels every two months with patients on mTOR inhibitors. If we start to see it rise, we start them on therapy. Many of my patients are already on statins, lipid lowering medications, but it doesn’t seem much of a problem in them. But if a patient isn’t already on, they can develop this.

Hematologic effects. The mTOR inhibitors can lower blood counts, create problems with white blood cell counts, and infections, more than VEGF inhibitors. As a class, mTOR inhibitors are not just used to treat kidney cancer. Long term, and in Europe, they have been used as immunomodulators for transplant patients. They change the immune cells in the body to prevent rejection of organs. For patients with kidney cancer, we change doses, but they can create changes in the immune system and put patients to be at risk for infections, like pneumonia. Doctors have to watch for infections when on Torisel or Afinitor.

A unique side effect to this class is interstitial pneumonitis–inflammation of the lungs. If it occurs, and causes symptoms of coughing or shortness of breath, we need to consider discontinuing therapy. More details on that.

A skin rash with Torisel is usually on the torso. We use a topical crèams, emollients with Benedryl. We try to avoid using steroids, as this drug already has an immune effect and we don’t want to add to it. With a patient who has grade 2, less than 50% of the body affected in a skin rash, I sometimes get a dermatologist to help. If the rare patient develops the grade 3, with more than 50% body surface affected, I would have to consider stopping the medication.

Hyperglycemia has been seen with both the mTOR agents, and we need to monitor blood sugar. Sometimes that means making the patients get a blood monitor, to check their blood sugar medications at home, or start diabetes medication.

Again you can see elevations in triglycerides and cholesterol requiring patients to start on lipid-lowering medications. Those are both reversible when you stop the medication.

We talked about infection. There is a chance of infection with the mTOR inhibitors, so we need to be on alert for that.

Seen here are CT scans of interstitial pneumonitis: in month five there was a development of this nasty-looking infiltrate in the CT scans. That scares everyone when we find this on a CT scan. It could be ones, one; an atypical pneumonia, two; interstitial pneumonitis, a drug side effect, or the cancer. Sometimes, we have to refer patients to a lung specialist for a bronchoscopy to determine what it is. In this case, it was a drug effect, not an infection, and it was not cancer. It was the actual drug inflaming the lungs.

They stopped the drugs, they gave a little burst of steroids, it went away. Later they rechallenged the drug, and the patient went back on the drug, without further recurrence of the interstitial pneumonitis. If I had a patient with interstitial pneumonitis, I would find it very hard to put them back on the therapy. I show this to demonstrate that it is a reasonable side effect to expect, and it is reversible. It manifests itself as an x ray finding or as a cough.

The general recommendations are as shown. Call if there is any side effect which you are uncomfortable with. It is better to call early so you can intervene on it before it becomes a problem.

END of LECTURE: Questions follow from patients and caregivers.

Patient responses; Patient suggests Rock Alum in the case of mouth sores.

4 Archway macaroon cookies, twice a day

Capcesin for foot sores

Doctor agrees that patients have much to offer help with some symptoms.

Questions re coconut oil, to be used for mouth sores; Doctor had not heard of that.

Side effects do get better, says patient, asking about taking acidodolphodus; doctor agrees that pro-biotics, yogurt, is helpful, perhaps to change gut flora.

Question re Zometa as it is used with Sutent; Zometa has benefit in reducing skeletal related issues, and would be beneficial with all the drugs, says doctors.

As to difficult skin issues, doctors suggest the use of anti-fungals and consults with a dermatologist.

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Filed under KCA Conferences, Lectures from Experts, Patient Resources, Your Role

by peggyrcc | May 22, 2012 · 5:37 pm

Kidney Cancer Stage IV : My Round Trip & A Foreign Language

Nothing catches your attention more than being told you have an incurable disease. Quick translation= “you’re dead”. All the words of encouragement, “we’ll do our best”, “you’re a fighter”, “the doctors could be wrong” are drowned out by the word “incurable”.

Doctors don’t like to answer questions like, “How long do I have, doc?”, and patients don’t like to ask such things, in my experience. But the internet and medical journals do give those answers, and rarely flinch when asked. The only real stats I can remember about my diagnosis of kidney cancer, or its more melodic renal cell carcinoma, was that about 37,000 patients were diagnosed annually the US, and about 13,000 died annually. Doing some quick math, I figured that I had three years, if I were lucky. It is now more than eight (Now TEN!) years.

Being diagnosed with terminal cancer puts you on a new journey, say the more eloquent of us. We welcome one another, remind them that this is all unknown, that it leads to a new country, the land of the sick, and certainly requires a new language. Five year survival, times to progression, overall survival, ablation, and retroperineal are the new phrases you encounter. In addition to those darn Latin words of endless syllables, that new language hijacks words we once admired, like “progression”. Progression once meant to go forward, like passing into the next grade, or getting the vote, surely good things. Not so. Progression suddenly means that the cancer is on the move again. Regression is the good word in this new language.

We can’t even pronounce half the words that are thrown around in this new world, and don’t even know that all the body parts under discussion. What is a collecting duct, have I always had a venous thrombus, and what is the difference between metastases, lesions, masses and tumors? Is positive one of those words that means the opposite of what it was?

Just as this new language swirls around you, the alien disaster grows insidiously, betraying all you trusted, someone tells you with great earnestness that you must now be your own best advocate. Isn’t the doctor supposed to be better at this than the patient? Does no one else find it ironic that the same body which produced the tumor in ignorance is now asked to defend itself, to be skilled and capable of fighting off the threat to life and to choose the weapons to do so. Am I now supposed to choose the meds and the techniques, advocate for one treatment over another? Hell, I don’t even believe that this has happened to me?

In my older world, advocates had causes and clients. They went to councils and boards, court rooms. To whom do I plead my case in this new world? And where is the court of appeals, should I need a new trial? Can I get new representation? Does my doctor even know what he is talking about? Of course, “trial” doesn’t mean what it used to, anyway. It’s more of a battle, with the weapons or medications being passed out to blinded patients by blinded physicians. Maybe half the weapons are dull or non-existent–placebos. Welcome to this new world.

There is no Stage V, of course. That is the ultimate “progression”, another form of “passing” that we talk about quietly and somberly. I wanted none of that, didn’t want Stage IV, for that matter, and yet I had been on that grim journey for many years. I had no early warning, not seen the road shift beneath my feet, nor learned the new language. I didn’t know if there were fellow travelers.

My cancer had probably started 8-10 years before my diagnosis, in some dark and poorly oxygenated part of my body, where some errant cell found a sweet spot to set up shop. Cells became a tumor, which became a mother ship, sending off colonizers, who found endless new sites in my lungs, “tiny tumors too numerous to count”. That eerie phrase from the CT report lodged in my head. No doubt, countless other tiny tumors, yet to be seen, were traveling throughout my body.

But now I am back home at what ever is called healthy, I may not be on any one of these apocryphal stages, hurling towards “progression”. Mine has been a round trip, or I have passed “Go” and have been able to collect my prize for the meantime. Of course, I do know that I am really just in a spur line along this journey. Sometime I am likely to be called back into the active mode again, but I will hear that alarm sooner than I did years ago, and I am now bilingual.

But eight (TEN!)years later, all the stats have changed. Rather than the 37,000, we now are quoted 57,000 (61,000) newly diagnosed patients, and still with the loss of our beloved 13,000. There are more of us, but we die less efficiently. Can that also be “progression”? How did I get home again? That story will be told soon.

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Filed under About Peggy, Glossary, RCC Basics, Your Role

Tagged as clear cell RCC, diagnosis, renal cell carcinoma, tumor growth

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The next side effect, mucositis or stomatitis, those are mouth sores. We can do a mix of things–tap water or salt & soda mouthwash, that baking soda kind of mouthwash, change toothpaste, as some brands burn.

Kidney Cancer Stage IV : My Round Trip & A Foreign Language

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