Category Archives: Patient Resources

Hereditary Kidney Cancer–Confusing but Critical!

Hereditary RCC: Genetic or Familial RCC


Most people are not surprised that there is no ONE thing called cancer. Tumors in all the organs or invasive cells in the blood or bones are referred to as cancer, but start when cells go wrong, whatever the cause.  As soon as you are told you cancer, whatever it, the quest begins to find out exactly which cancer it is.  With kidney cancer, or its more melodious name, renal cell carcinoma, there seem to be endless variations on what may be called kidney or renal cancer.  To treat it requires a very careful analysis of what is really is, starting with the pathology of the tumor when it is biopsied.  With kidney cancer that biopsy is usually done after surgery for the tumor. That biopsy will describe the shapes and type of cell in the tumor, which can be mix of types.  And then the real work begins.

A recent article in “European Urology” reviewed the mix of HEREDITARY renal cancers, those that arise due to one’s background. More common are the “sporadic” kidney cancer that could arise out of the blue or in response to some environmental toxin. There are ten Heredity Renal Cancers, or HRCs.  My goal is to alert the reader to the possibility that his cancer might be one of these. This would affect treatment, and may suggest the need to test family members.

If you have kidney cancer or RCC, you may be familiar with “clear cell” or “papillary” to refine the description of the cells in the tumors.  This may not be the whole story, as those HRCs—the hereditary kinds—may manifest a mix of ways, including as clear cell or papillary histology.

The most common HRC is Von Hippel-Lindau (VHL) disease, with both benign or malignant tumors.  RCC can be found in a 24-34% of VHL patients, appearing at mean age 39 years (far younger than non-heredity RCC), and often with multiple tumors and in both kidneys.  Cysts which appear not to be malignant must be watched–they have the potential to become malignant over time. Generally they are managed based on the size of the largest of these lesions.  Clear cell RCC is the one VHL-related subtype.

Hereditary papillary renal carcinoma (HPRC) is rarer, and typically occurs later in life.  Papillary tumors are the only phenotype with HPRC, and patients often develop numerous tiny tumors, 1000 or more.  These tumors are considered type 1 papillary renal cell carcinoma (pRCC) with a low nuclear grade, monitored with CT scans, and some do metastasize, though this is rare.  The MET gene is implicated in the growth of these tumors.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is newly identified as a HRC. Rarely do patients develop RCC, but are susceptible to developing multiple leiomylomas, which are generally benign.  When there is early onset of HLRCC, then RCC is found in about 20% of those patients.  These tumors can be aggressive, and about 2/3 display a papillary pattern.  Such tumors tend to be hyper-vascular.

Birt-Hogg-Dube (BHD) syndrome is quite rare, about 1 in 200,000 people, and thereby likely under diagnosed.  This raises the risk of developing kidney tumors, which occurs in 25-35% of BHD patients, and at mean age of 50. These tumors have varying histologic subtypes, generally chromophobe RCC or hybrid variants.  And there can be variants in the same tumor or within the kidney.  There is a risk of metastases, though rare. The characteristic skin lesions of BHD syndrome are not malignant.

Even more rare is Tuberous Sclerosis Complex (TSC), which can manifest itself in renal lesions, cysts and occasionally, RCC, the latter at a young, average age 28.  Neurologic complications can accompany this syndrome.

SDHB-associated paraganglioma/phaeochromoytoma is another heredity condition which may give rise to a mix of renal tumor, including clear cell RCC, chromophobe RCC and oncocytomas, i.e., a mix of histologically different types.

An HRCmay be suspected in patients with a family or individual history of renal tumors, in the instance of both kidney having tumors, or one kidney having multiple tumors or in early-onset renal tumor, i.e., under 50 years of age.

Clinical diagnosis can be further refined by genetic testing, and thorough review by an experienced uropathologist is fundamental to the diagnosis.  First consideration would be a VHL analysis and genetic analysis of SDHB and FLCN genes, as warranted.  Patients with type 1 papillaryRCC should be considered for MET analysis.  The presence of clinical symptoms related to any of the syndromes will guide the gene screening.  Testing on family members may well be warranted.

With these cancers, it is possible to have multiple lesions and affect both kidneys. Thus, treatment should preserve renal function and control the risk for metastases. Use of ablation to retain maximum renal function may be preferable to partial nephrectomies, for example.

Though these heredity renal cancers arise in a different manner than the more common sporadic RCC, the study of the molecular pathways provide some insight into new therapies for those patients as well.  Thanks always to those researchers who help in this struggle for information, as that is essential to provide treatments.

Peggy—Based on the European Urology 2010.

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Filed under Biological Systemic, Clinical Trials, Genomics & Genes, Immune Therapies Old & New, Targeted Therapies, Your Role

Morgan’s Morning Rant in the Hospital–“Treat Me Like a Person”

This young woman–aged 15–has just ‘explained’ in clear and articulate terms why it is so hard to get both well and respect in a hospital. Must it be this way?  Though it is referred to as a “rant”, that is not really the case–it is an indictment of the lack of respect for patients found too often in the health system.

Morgan has some serious health challenges, and has had to learn to advocate for herself to work to get better.  But the concerns she raises are typical for most patients, and the lack of coordination of care, and the lack of communication of care is huge barrier to getting well.  As do most of us, she understands that the failure to let her sleep is a barrier to that care.  And the further failure to let her wake up and be a part of her own care, communication symptoms, asking questions, is far too common.

I congratulate Morgan and her family for sharing this very important reminder.




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by | January 23, 2014 · 12:04 am

Medical Errors: It happens to doctors, too! Prevent and Protect

Delays in being diagnosed with my  kidney cancer may have led to it going to my lungs. Bad enough, but I had good care in my treatment–I think.  Rarely can a patient analyze his own care for errors.  No so with this guest writer, Dr. Itzhak Brook, whose story of his misdiagnosis and numerous treatment errors is one we should read.  With rare insight and passion, Dr. Brook is dedicated to prevent medical errors. The following is from his lecture at LSU Health conference in May 8, 2013.

 Preventing Medical Errors:

A Physician’s Personal Experience as a Laryngeal Cancer Patient

 Dr. Itzhak Brook: Guest Speaker at LSU Health conference in May 8, 2013.

Dr. Brook is introduced:  Dr. Brook has written 700 articles. He is an associate editor of several medical journals.  He is a member of the editorial board of several medical journals.

I have been very fortunate to serve with him in the “Head and Neck Cancer Alliance National Committee.” That’s where I got to know Dr. Brook, and he is doing some amazing work in terms of lobbying for head and neck patients to get their voice prostheses, electrolarynx, basic functional components that are not covered by healthcare.

Dr. Brook was diagnosed with larynx cancer in 2006. Two years later he had to have a laryngectomy, and he currently speaks with the tracheal esophageal puncture. He is the author of the book, “My Voice: A Physician’s Personal Experience with Throat Cancer.”  In fact, this morning he gave our department an inspiring talk on how it is to be a laryngectomy patient, and what we as physicians should look for. Dr. Brooke is the recipient of the 2012 John Connelly Medical Ethics Award by our Academy this year. Once again I would like to welcome him.

Dr. Brook speaks: “Thank you. It’s a pleasure to be here today and to talk to you about medical errors. First of all, I hope that you can all hear me. I have a very low voice when I speak.  I speak with the voice prosthesis. Here is a diagram of how I speak. I do this by diverting air through a little prosthesis into the esophagus and where the air and the  vibrations created allow me to speak.Slide2 This is my challenge: to be able to maintain the seal with this device around my neck which allows me to speak.  I wanted to talk to you today about my experiences as a patient with throat cancer and how I encountered many of these errors from nursing, then physicians while I was patient, and how I suggest we can prevent those errors by better education, patient advocacy, and how we can improve patients’ care.


It was shocking to me –when I became a patient to realize how common they are.  I have been a physician for more than 40 years, but I had never been on the other side of the stethoscope. As a physician learning on my own the seriousness of those errors, there wasn’t a day in which I did not notice two or three errors that were done by nurses, physicians, technicians, nutritionists.

It was psychological and physical strain to be on the watch all the time to try to prevent errors. I realized that hospitals are very dangerous places to be. Not that I didn’t know it, but this really illustrated how it’s a miracle that patients get out without more damage than they came in with. Indeed in surgery, it’s estimated that about a third of all patients end up with some kind of permanent or temporary damage because of mistakes.

Imagine how lucky that I was the medical professional, that I was able to observe those errors. The layperson is much more susceptible to them and cannot even correct them. Many patients are intimidated and are so grateful to us that they don’t voice their concerns or criticisms. That is why we don’t hear, and we don’t prevent many errors that can be prevented–even when they are observed. People like myself who have difficulties in speaking, especially after surgery when I could not speak for six weeks, are much more susceptible to such errors.

Slide6Let me share with you, first of all, what I saw in my own eyes as far as the errors I encountered. The first one that I noticed was that my physicians failed to recognize that my cancer had returned–even though I came to them with complaints of pain. They relied on an imperfect physical and endoscopic examination. They relied on the fact that the CT, MRI and PET scans were all negative.

But there was no substitution for a good physical exam which they neglected to do. What they should have done was asked me to do a Valsalva maneuver while doing an endoscopy, to breathe air and hold it and then look.  This allows parts of the upper airway, most specifically the pyriform sinus to open, which reveals an area that is otherwise not seen. My tumor was already an inch long and it was missed by CT, MRI and PET. That was an example that the diagnosis can be made in many cases by good physical exam.

The other thing that I learned is that some of the mistakes were because of the physician’s lack of experience.  My surgeons offered me a procedure which they had only done once before.  I was desperate to get the cancer out and neglected to think about it myself, as   “You need this procedure, but there may be people across the country who have done it hundreds of times.” What they told me is, “In surgery you see one, you do one, and you teach one.”  I believed it, but I know it now it should be, “You see 1000, you do 100, and then you teach one.”  This is the reality of the world.

As physicians, we like to help our patients, but we should know our limitations, and in fact, that we are not able to be expert in everything. It’s okay to admit it and refer patients to people who know more. Some cancers are so rare, like larynesophageal cancer, thanks to fact that less people smoke and drink, even at the Centers of Excellence, their number is limited. It’s okay to admit that some procedures are better done by those who do them more often. The fact that they removed scar tissue from me instead of the cancer speaks to my surgeon’s inexperience in the technique they used.

Another error I noticed was that my physicians wrote my orders in the wrong chart. Consequently I did not get the right treatment and I got therapy for another patient. This occurred in one of the best medical centers in New York City. You can appreciate that even in the best places mistakes do happen, and these are just a couple of several errors my physicians’ made in my care.


Nursing errors are more common and range from not responding to calls to forgetting to connect the call button to my bed. I was in ICU a day after my laryngectomy, and my bed was only three feet away from the nursing station. I was connected to five different tubes, IV lines, catheters.  Suddenly I was choking with secretions. I couldn’t cough them out so I looked for the button to call the nurse.  I could not find the button that fell to the floor because it was not attached to the bed appropriately. To save money the same nurse was serving two other ICU patients. My nurse was away. I couldn’t call for help. disconnected my PO2 monitor.  Nobody came. I disconnected the EKG monitors. I thought they would see a flat line.

Nobody came. Fortunately, my wife just happened to come in the morning, and she called the nurses to suction me.

Imagine that this can happen in ICU. You can choke to death! Not every hospital has one nurse for three patients.  When I was first hospitalized in military hospitals they had one nurse per patient. But in that hospital in New York, they were saving money. So here’s an example of a serious nursing error.

Slide9Some of the errors are listed here–like not washing hands, not covering the thermometer with the plastic cover, using the improperly sized blood pressure cuff, leading to alarming results. That meant I got medications to lower my blood pressure which wasn’t high, and administering the wrong dose of medication. So these are some of the mistakes.

There is a lot that can be done to prevent errors when better and uniform methods are used for training. Slide10

What is important is to adhere to certain standard of care. The rule now is to use algorithms and check lists.  Algorithms have been shown to prevent many errors. Simply by following the chart, you don’t forget about it; reviewing the records to detect errors and to admitting it and training the personnel to prevent it. There are people who keep making mistakes—those individuals should be retrained or even dismissed. They should be reprimanded.

It’s also important to have better supervision and encourage patient advocacy. Encourage patients to talk about those errors. Admit them if you think you made a mistake. Admit it and don’t try to wash it away. Admitting will prevent malpractice suits. Patients who see that the personnel acknowledged their errors will be less likely to seek reparation. If they don’t see it they are more likely to look for punishment.

Slide11  That is why open discussion is important. Encourage patient advocacy. Tell them the truth. Tell them the treatment plans. Let them be your eyes and ears, so they can come and correct, and tell you if something went wrong. It’s important to ask friends or advocates to help patients make the right choices so that mistakes are not being made. Encourage second or even third opinions. There is nothing demeaning about it. It will also make the patient know that you are there to help them choose the right treatment.

Slide12What patients should do is look for the experts in their illness field. Sometimes patients make mistakes by confusing friendliness with expertise. I made those mistakes. My physicians were lovely human beings, but still those that I initially saw did not have the best expertise in my illness field.

Ask for the true prognosis. Don’t be always optimistic, but realistic so if things don’t work right, the patient should know, recognize and accept it. What I tell patients to ask for, and you should also encourage them to do is to give you their best history. The more you know, the easiest to it is to prevent errors. All the past history, all the little nuances that patients can tell will help their doctors make the right choices. Also what I ask the patient to do is to challenge us. Ask questions. Don’t dismiss these questions. We the physicians should not overshadow our patients. Let them ask. They may not always know something. Tell your patients, “Don’t assume that we the doctors know everything because we don’t.”

Medicine is as much an art as it is science. If the patient has an advocate, they are going to be more likely to catch errors and explain and ask questions, especially when the patient is sleepy or sick. Have a friend or family member be there and challenge us if necessary will prevent errors.

All physicians including surgeons need to listen to thire patients. We are all overworked, but we need to recognize how overwhelmed the patient is. They cannot always make good judgments. They are scared. They want to be saved and helped and they don’t always ask the right questions. You need to let them have time to question you, to challenge you. The more explanation you give, the better they will be in helping you prevent mistakes.

Don’t forget to examine the whole patient, not just the area where you specialize in. I especially ask my surgeons to examine on the entire body.   I asked my surgeon to listen to my lungs, he said, “I really wouldn’t even know how to do it that. I’ll call the internist.” I was shocked o hear it, but at least he recognized it as his shortcoming.Slide15

You need to remember the patient is made up of body and mind. Don’t forget to think about the patient’s psyche as well and the all other issues that are psychological. They all contribute to what we call the whole patient. It’s important to recognize thoseissues and educate the young medical generation, the residents and fellows about those issues. Residents follow us, the attending. If they see us, the attending, to be patient and concerned they’ll do the same. That’s why it’s important to follow those guidelines

It is important to educate the young generation to make sure they develop good treating habits and will care for the patient and will catch errors and be more humane and caring.

I summarized a lot of what I talked about today on my blog which is listed here (  where I discuss also medical errors.  I have a page on my blog that discusses how to prevent medical errors and what were my own experiences.  This is a difficult, and a challenging topic. We can prevent many of those errors by encouraging better adherence to standards of care, patience, vigilance and advocacy.  By preventing making mistakes we will get better results and better patients satisfaction.

I want to thank you for your attention. I will be happy to answer your questions. Thank you.”

Questions from the audience:

Audience; “One of my observations and thank you for presenting. My observation is that one of the major problems with medical errors is that most people don’t care or they think it is someone else’s responsibility. We don’t recognize our responsibility. Something else to the younger generation: they need to they need to feel confident enough that they will allow patients or advocates to challenge us. There are many physicians who are either overly self-righteous or afraid that when they’re challenged, their entire being has been challenged. They don’t feel comfortable enough to have a discussion like that with the patient or advocate.”

Brooks: “You are correct. Many physicians are threatened. Many come in today with the Internet more knowledgeable. Many patients know a lot about their illnesses and the more I think: the more they know, it is better. On the other hand, there is lot of false information that the patients have through many sources of knowledge that are not perfect. I think that we should encourage it. I don’t think we should see that as a threat to us. Get patients, let patients challenge us.


I can tell you that as patient I was afraid to challenge my doctors. I was so grateful initially that they were taking care of me, that I was afraid that if I would challenge them, they wouldn’t give me the best treatment. It may sound strange, but I was afraid. I was afraid that they will label me a troublemaker. So I kept silent. I was silent anyhow, but at least I didn’t say anything in writing. As the mistakes accumulated, I realized that “If I don’t speak out, I will not get out of this place as healthy as I could”, and I started to speak out. My luck was that my daughter was my voice for a while, until she had to leave. She was my patient advocate.

But many patients are threatened by us even if we are nonthreatening. But we can try to disarm them and create an atmosphere of less threat and can encourage them to talk instead of being defensive. We would say okay, let me look into it and let me do something to about it.

One of the most humiliating episodes that happened to me occurred when I was recovering from my laryngectomy. That one morning the residents were making rounds.  I had a laryngectomy tube—which was completely clogged with mucus. The nurse usually came and cleaned it, but she hadn’t yet. The residents got there first. So I asked a resident to clean it. I was shocked when he took it out without gloves, went to the faucet and flushed it with water.  I refused to let him put it back in my trachea – in my tracheostomy. I wrote to him, “This is not the way you should clean it. You need to open a kit and do it.”

He said to me, “We are running the show now. This is how we do it.”

I was so helpless I couldn’t do anything except refuse him from doing it. When I mentioned it to the attending (physician) when he came, he told me “Oh, this is resident is very nice. He would never behave like this. I can’t believe he did it.”

I didn’t hear anything more about it. So there was an example of the mistake. You don’t clean it with tap water! You have a kit. You need to wear gloves. This is also an example of arrogance. There is no room for arrogance.

Now if I was in a position to do it, if I could walk, I would go to the hospital director and complain but I was a sick, helpless patient. Here is an example of how a patient can’t do anything. He is completely at the mercy of staff and mistakes that are being made. So I think there is a need to better education, for greater humility, and less intimidation.

Also there are places where the nurses are not as well trained. I noticed a difference in the quality of nursing. When I was hospitalized at the Naval Medical Center in Bethesda I noticed that the nurses were young but very well-trained. Everything was done according to the book. However, when I was hospitalized at Walter Reed Army Hospital, I found out that about two thirds of the nurses were civilians, from many places. Some were good, but some were not.  Some nurses were well-trained and some were not. You need to make sure that everybody is following the same procedure and that is best way to prevent mistakes.

Audience: “I think you need to go around the whole country to teach us about this. This is the tip of the iceberg. You are a physician, you are an insider, you know what happens there so you can say I have a job I don’t do much. The problem is the education that you mention. To be critical, you have to suffer pain. People like to be praised all the time, “You are doing a good job, you are doing a good job.” If one harms you, say at this time that it is wrong, so the next time you praise will be appreciated.  You’re coming from a high school, a college, medical school and something and so, and told. “Be nice, not to be critical” We are not critical enough. The problem is big!”

Dr. Brook:  “I couldn’t agree with you more. It’s important. At one point I said enough, I guess I’m not going to be a nice guy anymore. I am going to take the gloves off. I am extremely grateful to everybody and I say it to them. But on the other hand, I realized that we are all human beings. We all make mistakes. It’s not a perfect world and the only way we can prevent it, reduce it, is to have check lists. We need a system that reduces it. One thing is to have lesser burden on the physician, lesser burden on the nurses, so that they are not overwhelmed, so that they don’t make mistakes because they are tired and overworked.

We should have a system where people are encouraged to admit and discuss mistakes openly so we don’t repeat it. We have in our own hospital such a venue where we meet once a month and we talk about the mistakes we made–without accusing anybody, without reprimands, just to talk, to prevent the errors from happening again.”

Audience: “We have to listen to what you are saying…The part I found most important for young doctors, that we have to emphasize over and over again is the importance of a good history and a good physical exam.  Some of our younger doctors think that a physical exam is complementary to the technology and it should be the other way. Technology should be complementary to the physical exam.   We are missing a lot and need to go back and listen again sometimes you have to remind yourself that just because we have CT scans and PET scans, it’s not the same as talking and having the doctor patient relationship .

Dr. Brook: “I agree that we forgot the art of medicine over the years. I remember when I went to medical school in the 60s, how my teachers were really true clinicians. They could examine the patient and listen to them and talk to them and they were able to find things. Today people forgot the art of medicine. I believe that even today 95% of the diagnosis can be made by doing a good physical examination. Unfortunately the new technology made us rely on tests and scans and in this way we spend less time with the patient and that course also leads to mistakes.

Audience:  “The question I have for you is with cost being such an issue now, I think, what are we to do with less staff when there’s still a need for extra eyes?”

Brook:  “I think there is no substitute for more staff. When someone is out of surgery in the ICU and in critical condition, you need a person there.  I don’t think there is a substitute for that. I wrote about those episodes in my book. There was an episode when I was mistreated because of lack of personal. I had a skin flap removed from my hand to create my new esophagus. That flap needed to be constantly covered. The nurse was in the process of changing the cover when she had to suddenly leave my room because she had something else to do. I was lying there for about 20 minutes. I couldn’t call anybody. When I finally got somebody, they told me, “The nurse is on the phone ordering something.”  A resident physician who came to complete the change was called away by the attending. Nobody seemed to care that I had tremendous pain for another  25 minutes. There is simply sometimes pure negligence that happens.  The only thing I can tell you is that a patient advocate is so much needed. I know that if, God forbid, anybody of my family will be in the hospital, I will not leave their side 24 hours a day. Fortunately, it didn’t happen to me yet but if it will, I will not leave their side.”Slide14

Audience: “What I think this episode reveals is simply what Dr. Mary says, that there is a loss of professionalism amongst everybody involved in healthcare. There the physicians, I think have forgotten that they’re in charge of everything. We do need to hold everyone accountable. The nurses have forgotten what their true training has been in. Everybody has focused on getting the work done as quickly as possible so they can get onto the next thing. It has left the medical profession in the dark.”

Dr. Brook: “I agree with you. People are so overwhelmed. Sometimes when I wanted to talk to a physician (by writing because I couldn’t speak) he would dismiss me, “I’m really very busy now, I have to run to my clinic or I have to run to the OR. If you like, have your wife call me.”

I had one mistake that happened because the doctors wrote an order for another patient in my chart–to start feeding me one week after the surgery. It seemed to me very strange, because I remembered that my surgeon told me that I will be starting feeding two weeks after the surgery.  I protested, but then I thought, “Maybe it is all right. I’m happy to eat again”. Only because I questioned it again and again, did they finally stop it–twelve hours later when they realized they made a mistake. I was fortunate that no bad thing happened because of it even though after getting the type of surgery I had, it was dangerous to be eating too soon. Here is an example of an error and I don’t even know if there were any repercussions because of it!

I wanted to let you know that you that you could read my book, “My Voice: A Physician’s Personal Experience with Throat Cancer”. It’s available for free on the Internet at my blog and also you can get it from the American Academy of Otolaryngology website ebooks site at


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It’s Spread! Is It Too Late to Do Anything?

I love this study, as it really symbolizes the tremendous change that has occurred in kidney cancer treatment these last 6 years. It is remarkable that the 124 patients are described as having already received first- line treatment, and were now in their second-line. These same metastatic patients might have received neither just six years ago.

The study was really not to compare the response to the treatments received, whether Sutent (sunitinib),  Nexavar (sorafanib), or placebo.  (Why any party chose or was chosen to receive a placebo is another, darker question.)  That the median follow-up was 80 months is a triumph by itself.  This is in contrast to the clinical trials that often show just a few months extra time which we and politicians can focus on, when the reality of much longer responses is clearly shown here.  Of course, these longer survival times came from those trials which showed those few months–and this shows the reality of many more months and years of life!

Metastatic tumor burden(TB) was measured, based on the size of the sum of the longest unidimensional diameter of each targeted lesion.  The additional increase of 1 cm (about 3/8”) was significant in predicting response to the medications. Siimply, adding the one-direction measure of the lesions and comparing them showed that more tumor was a bigger problem.

One can also assume that to remove as much tumor as possible may be helpful in maximizing the benefit of the meds given, although this study does not address the actual types and locations of the mets, nor indicate why no other therapies, surgery or ablation, were used.  With 124 patients this would represent a mix of individual experiences, more like the typical patient group.

What does “median follow up of 80 months” really mean?  A median is not an average, but a measure of the time point at which ½ of the population studied had follow up less than 80 months and ½ had follow up for more than 80 months.  Since this is considered a long time in clinical trials and becomes more of a longitudinal study, we may never know the average length of time that these patients had either PFS (Progression Free Survival—time until the mets began to grow again) or OS (Overall Survival).  In any case, we are aware that following this second-line of treatment, there are still more therapies and interventions which may be available.  And even more options are up for FDA approval as I write.

All these options and the greater success of each muddies the study waters, but clarifies the hopes of those with metastatic RCC, or are at risk. This study proves that tumor burden (TB) is a disadvantage. Most patients have naturally assume that more cancer is worse for you than less cancer—who knew? But this gives weight to the notion that the removal of some tumors, if not all, can be beneficial used with targeted therapies. In the past, some oncologists have discouraged additional surgery in the light of metastases, with the implicit message, “It’s too late, and won’t help you anyway.”  Not the doctor for me.

The story is quite different right now, but patients may need to tell this to their doctors–in the language that the doctor speaks. Certainly, there was a time at which doing more surgery for mRCC patients added little, if anything, to survival and probably even less to the quality of life. That no longer is the case, and those older studies no longer have meaning.  While each patient must be treated as an individual, in light of all the variables that impact his health, there is increased optimism for the metastatic patient. Aggressive and early treatment can no doubt extend life and make it worth living.  


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Filed under Ablation & Radiation, About Peggy, Biological Systemic, Clinical Trials, Immune Therapies Old & New, Medications, RCC Basics, Surgery, Targeted Therapies, Your Role

My Family’s Difficult Struggle Through Cancer;

Every family who encounters cancer has a struggle, but nothing seems harder to bear than the stories of those who are hit when they are especially vulnerable.  When I was diagnosed, my youngest was barely 17, but the others were grown and independent.  When cancer hit this family, they had a newborn.  Against all odds, this a success story, and one which reminds us of the value of love and strength.  I introduce the story of Cameron Von St James and his wife Heather, in this guest post:

“More than once, my wife has made the comment to me that she doesn’t know how I coped when she was diagnosed with cancer. Her mesothelioma diagnosis came only three months after she gave birth to our daughter Lily. What was a joyful, happy time in our lives turned quickly into a time filled with fear and uncertainty. When Heather’s doctor told her about her cancer, I looked at her, and she broke down crying. I didn’t know how we would get through this.

I was so overwhelmed with emotion. I was on the verge of breaking down when the doctor’s words brought me back to reality. He was talking about making medical decisions for my wife, and I knew this was just the beginning. It was the first of many days where we would be forced to make impossible decisions while going through overwhelming emotional turmoil.

My overwhelming emotions didn’t stop there, however. Following her diagnosis, I was angry at the world.  I felt like it wasn’t fair that we had to go through this. For a while, I often lost control and lashed out at others. I used a lot using profane language. It didn’t take me long to realize how selfish I was being.  The last thing my wife needed was to see just how scared I really was. I knew I needed to get it together and be strong for Heather, but it was so hard for me to do. When I was able to do it, I finally became the rock that she needed.

I was still overwhelmed with the new responsibilities that fell on me. I had a mile-long to-do list that included everything from travel arrangements to work to taking care of my house and family. I wouldn’t have been able to get through any of it without the help offered by our family and friends. I learned to prioritize and to first get done the things that were most important. I was still overwhelmed even with all the help, but I managed to get through it.

The hardest part of it all was sending Lily and Heather to South Dakota for two months following Heather’s surgery in Boston. I knew that I couldn’t work and take care of Heather while she recovered, and that’s what forced us to make this difficult decision. Heather’s parents in South Dakota offered to take care of them while Heather recovered and prepared for the next round of her mesothelioma treatment, and we decided to accept the offer. During that two-month period, I saw my family only once. I left work on a Friday night and drove 11 hours in a snowstorm to see them. I had to make the 11-hour drive home that Sunday so that I could be back at work on Monday morning.

What I learned through all of this is how lucky we were to even have difficult decisions to make. I was so lucky to have the help I had from all of our friends and family. I couldn’t have done half of what I did during this difficult time without their help. You have to accept help when it is offered to you during times this difficult. It’s been six years since Heather was diagnosed, and despite the overwhelming odds against her, she’s happy and healthy now, and cancer-free. I only hope that my words can help someone else who is going through cancer.”

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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. No 1 Triple CT 1 18 2011 crop edited 626

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?No 2 CT 1 19 2011 crop 4074

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 3 CT scan Lit Co Mary crop

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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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!

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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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Friends from Cancer and Other Surprises: Honoring Frank Friedman

When I found out that I had metastatic cancer, I never felt that would be any benefits or pluses from that devastating news.  All I could think of was the loss and pain and fear that this brought at that instant, and would do again and again.  Though I was disbelieving that I was sick–I didn’t have time to be sick, I was supposed to be the caregiver, I had never even heard of kidney cancer–deep in my heart I knew that nothing good came from cancer.

I was wrong.

Much in our lives isolates us and alienates us from others.  But there must be something innate in human beings who recognize new members of their families. Hearing a familiar accent, seeing a college logo or tasting something Mom used to serve draws us together and motivates a quick smile or conversation in a warm and satisfying way.  Who knew that cancer would do that?

Out of my cancer experience, I found such a connection in Frank Friedman, who had such a loss to kidney cancer that he has reached out and befriended not only me, but hundreds of people–perhaps more.  Frank lost his only child to kidney cancer, and from that grief grew the determination to help others who were hit by this disease.

Sammy was only 38 when he died, and quite young by kidney cancer statistics.  But this disease which does not f0llow any rules, and does not respond to the standard chemotherapy  and radiation generally used to fight cancer.  The one rule seems to be that it is not diagnosed early enough, and is usually an “incidental finding” while looking for a broken rib or such.

To help deal with this loss, Frank and his wife sought others who were similarly affected, but could find no support group.  Being a professor, then retired, Frank naturally took action, and started such a group.  Of course, the emphasis is on education, which can be of tremendous value both to patients, their families, and physicians.

Through Frank’s efforts the governor of Michigan has declared March to be proclaimed “Kidney Cancer Awareness” month.  No doubt many people have found their disease, and acted upon it quickly, preventing the disease from advancing.

This is a labor of love, but also a labor of time and imagination.  To find speakers who can reach out to patients, to find patients who are not yet served and to acquaint doctors of this new resource–and to remind them of the under diagnosed and misdiagnosed history of kidney cancer, Frank spends countless hours of his own time.  He handles all the meeting arrangements, produces and distributes flyers to community centers and doctors’ offices, invites other like-minded groups and personally reaches into the hearts of others.

How did Frank and I meet?  We really never have, except through the internet, which brought us together.  Frank is very active online, though is he hardly of the “wired” generation.  Too often those of us old enough to be born in the first half of the last century–I call us “adults”–are thought to be disinterested or incapable of using this new mode of study and communication.

But leave it to a father and professor to reach out to teach and nuture!  I honor Frank today, which happens to be his birthday, with this acknowledgement of the gifts he has bestowed, not just on me, but so many others.  Not only has he befriended me, as I add my efforts to this fight, but to many others, and not just with kidney cancer.  Join him and his group through his open Facebook account, “Kidney Cancer Support Group of Michigan”, or reach him directly by email at  You will gain a new and loyal friend.

Happy Birthday, Frank!


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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 3rd.  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.


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.


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