Doctor's Note 03-31-09

It is with sadness that I am reporting the passing of our patient and friend Kevin Brock. Kevin passed away February 18, 2009 at his home in Richmond Kansas with his parents and family members at his bedside.

Kevin was initially diagnosed with metastatic melanoma in 2002, when he presented with a melanotic lesion in his left calf. After resection of this lesion he had a sentinel lymph node dissection in the left groin. Unfortunately he had lymph node involvement. Kevin spent a year receiving adjuvant therapy Alpha Interferon. He was disease free until June 2007 when he developed subcutaneous skin lesions in the neck and under the left axilla. These biopsies were positive for metastatic melanoma. In the ensuing months he received two different trials of chemotherapy, none of which worked. He developed rapidly progressive skin lesions throughout his body. As a last resort, the FDA allowed us to give Kevin our vaccine on a compassionate basis.

Kevin is the first person to receive this vaccine. He started the vaccine therapies in March 2008. At that time, Kevin had five index lesions that were measured; these were all subcutaneous lesions (under the skin). Within two months of treatment four of the five lesions disappeared completely. The fifth lesion was excised and we found a hematoma (blood clot) and very little residual cancer. Kevin successfully completed two cycles of the vaccine treatment. He had very few side effects from the treatment. He did have some intermittent joint pain which responded to Aleve and Tylenol.

Kevin developed new subcutaneous lesions within four months of completing his vaccine therapies. The recurrence was much more aggressive, and Kevin developed more than six nodules in one week. By October 2008, these lesions were rapidly progressive. After extensive discussion with Kevin and his family we decided to give the vaccine another try. Once again the vaccine was effective in controlling the older lesions. This time around despite vaccine therapy, new lesions were developing under the skin in various places of his body. It seemed like the vaccine was able to control the older lesions but not prevent the development of new lesions under the skin.

I discussed alternative treatments, such as experimental clinical trials at other institutions. Kevin was tired and declined further treatments. Following the Christmas and New Year Holidays Kevin was admitted to the hospital. He received radiation treatment to some of the more painful subcutaneous lesions. An epidural catheter was placed in his back with a pump that would deliver pain medication continuously. He was then dismissed home to the care of his parents with Hospice support.

With the experience of treating our first patient with the vaccine we have learned some valuable lessons. It appears the vaccine is well tolerated with very few side effects. Joint pain which is easily relieved with Aleve and Tylenol seems to be the only major side effect. In terms of efficacy and benefit of the vaccine, this would be too difficult to assess with one patient. However, Kevin did respond to the therapy, however briefly, and our future assessments may need to include a period of maintenance therapy with the vaccine. Kevin was a kind and courageous young man whose fight to find a cure for melanoma has already aided us in improving our treatment protocol and ultimately curing melanoma. Kevin will be missed. Listed below is Kevin’s biography (reproduced with permission).

Kevin was born on May 13, 1976 in Garnett, Kansas, the son of Jerry and Marie (Peine) Brock. He graduated from Central Heights High School with the Class of 1994. Immediately following his graduation Kevin was a dedicated employee of Jarit Industries until 2003. After leaving Jarit Industries, Kevin was happily employed by Performance Electric until his death.

Probably the best way to describe Kevin to those who were not lucky enough to have had the pleasure of knowing him would be to simply say that he was truly “special.” Kevin was dedicated to his family, to his work, and to his friends. He was one of those very rare people that just make everything better with their presence. Kevin’s coworkers have said that they enjoyed going to work simply because Kevin was there.

Kevin measured himself not by how much money he made or how popular he was, but by the things that he did for others. On his list of priorities Kevin always placed himself behind his family and friends. If ever you were in need Kevin was there to lend a helping hand. From building a deck to finishing a basement, or even just an open ear Kevin could not say no. When Kevin’s help was enlisted it could be assured that anything he did was done right. Kevin took pride in the work that he did and would not stop until the job was completed to his satisfaction.

Lazy was not a word that could be associated with Kevin. For him there was always another project that he volunteered to help complete. During his life Kevin was a metal worker, electrician and a plumber. No matter what the task before him Kevin would not stop until he had achieved his goal. Whether it was his epic battle with cancer or finding the solution to a problem which lay before him, Kevin was a fighter who always refused to quit. During his life Kevin had probably endured more pain than any three people combined but he never felt that his situation was unfair or felt pity for himself, he simply continued on no matter how bad it hurt.

The foregoing paragraphs focus on Kevin’s work ethic, caringness and dedication. Although those sections may reveal the source of some of our admiration for Kevin, they do not tell a complete story of his life. Kevin’s greatest joys in his life were his family, friends and dog, Keisha. He especially enjoyed the time he spent with his nephews; for them a kinder, more caring and loving uncle could not have existed. One of Kevin’s joys in life was to provide homemade gifts for his family and friends. Kevin’s creativeness in developing these gifts and the method in which he gave them is beyond comprehension to those who have not been witness to the event. We will always have our cedar chests, toy boxes, lamps, etc. to remind us of him.

Now that he is gone we are left only with those cherished memories we have made with Kevin while hunting, fishing, or just spending time with him. To those of you who knew Kevin, may your memories of him be long lasting and pleasant; to those of you who did not, just know that Kevin was truly “special.” This world is a lesser place without Kevin in it. Though his time has passed he has left his mark in the memories of those of us who were lucky enough to have known and loved him. Kevin, until we see you again please accept this small tribute to you and know that it does not do your memory justice.

Doctor's Note January 16th, 2009

Kevin had a good Christmas and New Year with his family.  Shortly after the New Year, he developed new subcutaneous nodules in both thighs and pelvis.  They are causing considerable pain, and making it difficult for him to walk.  He is undergoing radiation treatments to these sites of disease.  For pain, he has an implantable epidermal pump that is keeping the pain under control.  Kevin does not want to undergo any further therapies.  Kevin finished his vaccine therapies in November of 2008.  None of the old lesions have recurred, but he has multiple new subcutaneous lesions. The lesions in the pelvis and thigh are causing the most problems especially pain.

A note From The Dr. as of 10/01/08

With Kevin’s treatment with the melanoma vaccine, I have had a lot of inquiries about how our vaccine was developed and about how Kevin was screened to be our first candidate for the vaccine. 

Our vaccine project was one of many different areas of research I have been engaged in over the last twenty years.  In my graduate school training in immunology at the University of Kansas Medical Center (1977-1981) I was involved in studies looking at the immunology of cancer patients.  At that time, my research focused on aspects of the immune response when cells become cancerous.  Specifically, I was involved in deciphering receptors on the surface of immune cells that would interact with cancer cells.  My graduate thesis was a description of these receptors in patients with a type of blood cancer called Chronic Lymphocytic Leukemia (CLL).  Since my completion of graduate work, I continued to have an interest in the immunology of cancer as I proceeded through my medical school training and the post-graduate clinical training that ensued.  After joining the faculty at the KU med center I started to investigate the topic of the immunology of cancer.  I was fascinated to learn that cancer patients had a completely intact immune system in most instances.  The big question is why does cancer survive in the body in an environment where the body can recognize cancer cells? 

One of the clues turns out to be that the immune system is unable to find the cancer cell in the body simply because there are millions of normal good cells in the body, like trying to find a needle in a hay stack. I conducted a series of investigations looking to see if the immune cells could be taught to easily identify cancer cells and direct them to the process of elimination of these abnormal cells by inciting an army of other immune cells to be commandeered to the cancer site.  Along the way I deciphered the various rules that the body had for activating the immune system to destroy the cancer cells. 

With the help of computer models we have been able to look at various proteins and peptides (short segments of proteins) that could be used in this activation process of the immune system to get an idea of what proteins would work in activating the immune system.  The reason for using a computer-based approach is that we can exhaustively test thousands of proteins and peptides without having to do the laboratory work.  After narrowing our search down to a few potential proteins, we then tested these in animal models.  We used mice and subjected them to injections of cancer cells into their bellies and then challenged them with various vaccines that we developed based on our knowledge of their computer-based benefit.  Our results were startling.  Our experience with the animal model reflected our predictions based on our computer analysis.  Armed with this information we refined our vaccine and in our final testing, we found 19 out of 20 mice survived the cancer challenge when given our vaccine.  But, when offered other vaccines they succumbed to the disease.

Now we wanted to test this theory on patients, specifically those patients who had advanced melanoma and had exhausted all other treatment options including chemotherapy.  To offer the vaccine to our first patient required a lot of careful screening.  Because the vaccine had never been tested on a human being, we had to make sure all safeguards were in place.  This included approval by the Human Subjects Committee and approval by the Food and Drug Administration for use of this vaccine on a compassionate basis. 

Our first patient, Kevin, was no stranger to me.  Kevin, now age 32, has been my patient for over ten years.  When he was originally diagnosed with melanoma he had an abnormal mole in his left leg and he had surgery for it.  Because this melanoma was aggressive, he also had a second operation that resulted in wide excision of the skin in the area of the mole.  Additionally, the surgeons dissected the groin area to remove lymph nodes from that site.  Unfortunately for Kevin, the melanoma had already spread to these groin lymph nodes.  He had advanced melanoma.  Kevin received a drug called Interferon that had been shown to be beneficial for melanoma patients.  He spent an entire year receiving interferon injections every week.  The treatments were not easy and he experienced many side effects including fever, chills and flu like symptoms.

With this treatment, however, Kevin was in complete remission and the remission lasted for ten years.  Unfortunately, in the last year Kevin developed multiple nodules under the skin.  Biopsy of a nodule showed that this was metastatic melanoma that had come back after ten years of being disease free.  After extensive discussion with Kevin, we decided to proceed with chemotherapy.  Kevin received six months of chemotherapy.  We evaluated the response to chemotherapy every two months.  Initially he did have a good response, but by the end of the six months of treatments, he had failed and was suffering many complications from the chemotherapy.  He was losing weight, he was fatigued all the time to a point he could no longer work.  He had changes in taste and he had no appetite.  He had numbness and tingling in his hands and feet which is a side effect called peripheral neuropathy.

After completing six months of chemotherapy, Kevin needed a break from treatment.  He needed to recover some of his strength, improve his strength and stamina.  During this period, we worried about disease progression.  Metastatic melanoma can spread to vital organs like the brain, liver, lungs and bone.  We immediately set about to look for another alternative to chemotherapy treatments.  After exhaustive discussion and review, I thought that Kevin would be a good candidate for the melanoma vaccine.  Kevin was also enthusiastic about trying the vaccine.  Because of the experimental nature of the treatment, the treatment was offered to him at no cost.

Kevin started his treatment on St. Patrick’s Day, March 17, 2008.  The vaccine was administered by an intramuscular injection.  The initial series of injections were given three times a week for two weeks.  At each clinic visit wee exhaustively queried Kevin about potential side effects.  The intramuscular injections did cause some pain.  On the day following the injections, he did experience some low-grade fevers and some flu-like symptoms.  He also experienced joint pain in the joints closest to the injections sites.  We rotated injections so that different limbs were used and the joint pain would follow.  With each injection we carefully measured the different tumor masses that we could feel under the skin.

Kevin started with five lesions and three have disappeared.  The fourth lesion is continuing to shrink.  The fifth lesion however, increased in size.  This was puzzling to us.  Because this lesion was in the armpit and close to the skin, we asked Kevin’s surgeon to excise the lesion.  The pathology on this lesion is now available.  The findings are that a large part of this lesion has necrosis (dead cells) and hemorrhage (bleeding).  Only a very small part of the lesion is occupied by melanoma.  Our inference is that this lesion with melanoma was also responding to the vaccine therapy.  The reason we believe it appeared to be enlarging was the hemorrhage and necrosis.  So far, all five of the index lesions with melanoma have responded to the vaccine therapy. 

Kevin is continuing to undergo vaccine therapies, and we will provide further updates as they become available.

 

Sunday October 26

Sorry its been so long it seems like its just been one thing after another first I had my surgery then I had my test and drinking that stuff for my catscan made me sick,then I got a real bad cold where I lost my voice for about a week,but I think I'm better now,for awhile anyway.
I got all my test results back and they found some spots in my chest,neck,lymphnodes under my arm,and brain.The ones in my brain the doctor's not sure what they are because they are so small and they keep comming up and then going away.The scans show that the ones I already had have grown and all the ones under my skin that I can feel but the scans don't show have grown to.
I was going to get to try to do treaments every other week,but since my scans came back like they did I am going to keep going once a week.The second batch of the drug that I got the doctor thought that if he froze the drug it would keep better,since all of my scans came back the way they did and all the ones under my skin have grown also I started last Thursday with a new batch and he is not going to freeze it this time,because in the begining when he did not freeze it ,it seemed to be working better.

A Note from the Doctor as of: 09/21/08

Kevin has been seeing us in clinic every week, and I have been monitoring his progress.  In general he has been tolerating the vaccine well.  When he started his injections, he did complain of joint pain. Those symptoms have improved since the initial injections.  To measure the effect of the vaccine we have been monitoring 5 melanoma sites on Kevin’s body which are easily felt under the skin.  Three of the five lesions have completely disappeared.  One is continuing to respond as it shrivels up.  The fifth lesion has not responded and remains at the same size.  We are planning to have this lesion removed to try to find out why it is not responding to the vaccine therapy. 

            Kevin has returned to work and is able to do most of the activities required of him as an electrician, however, I have asked him to refrain from working on high platforms because of his intermittent headaches.  His headaches precede the diagnosis of melanoma.  We have performed an MRI of his head and a lumbar puncture to analyze the spinal fluid.   Findings suggest he has no melanoma spreading to the brain.  It is comforting to know that though Kevin continues to have intermittent headaches, they likely are not from melanoma spreading to the brain. 

            We have also been analyzing antibody titers from his injections.  The purpose of this is to determine how well his immune response is to the stimulation from vaccine injections.  Kevin has had an excellent response and his antibody titers are high.  This means that Kevin’s vaccine injections are stimulating the immune system to respond by producing specific antibodies that are directed against antigens on the melanoma cells.  These antigens are what differentiate melanoma cells from healthy cells in the body. 

            Our vaccine is produced by combining melanoma specific antigens with a carrier molecule so that the body’s immune system will recognize it as foreign.  The carrier molecule is a protein that is found only in crustaceans like crabs.  This allows the body to recognize these proteins as foreign and in the process produce an antibody response that will cross-react with the melanoma antigens that have been coupled to this foreign protein.  Laboratory research showed this theory to be plausible, and the vaccine appears to be working for Kevin. 

Kevin has had CT Scans from head to foot looking to ensure that he does not have any internal organ involvement of his melanoma.  To date, his melanoma has remained only in areas under the skin that we can readily feel.  We are encouraged by his response to the vaccine therapy.  His response, so far, will be characterized as a partial response.  With the removal of the fifth lesion, we will continue to monitor the fourth lesion in the hope that it too will disappear. 

 

Dr. Raj Sadasivan M.D., Ph.D.

Hope Cancer Institute, Inc.

4215 Shawnee Drive

Kansas City, Kansas 66106

 

Phone: 913-236-6986

Fax:    913-236-9681

Thursday September 11

Last time I talked to you I was going to get a spinal tap and I did and everything came back good there are no cancer cells in my spine. I also did my MRI of the brain this last Saturday and just met with the doctor today and they only found one of the four spots in my brain and it is a little bit smaller than the previous scan so that is very good news. I have always had one tumor that has not responded to the treatment and has never shrunk and has slowly grown when the rest of them have either went away,shrunk or did not change so now the doctor wants me to have surgery to get it removed so I guess that is the next step.
Tami and Rae it is always nice to hear from you since we never get to see each other its been along time,thanks for the thoughts and prayers.

Sunday August 24

I'm sorry its been so long since my last entry,but for awhile everything seemed to be going great and the doctor decided I would just do a booster shot every 3 months so there was'nt a whole lot to tell.Then when I was only A couple weeks away from getting my booster shot I found another spot and started having dizzy spells every so often.I then went and talked to the doctor and he decided to start treatments back up for once a week.A week or two after starting treaments back up I found a couple more spots and the doctor decided to have me get an MRI to see what was causing my dizzy spells.When I got my results back they found a small spot on brain and then a month later they had me do another MRI and they found three more small spots,but they said they were so small that the scan could have missed them the first time.After a couple weeks into the treaments I have'nt found any more new spots. He is going to have me do another MRI in a few weeks to see if any thing has changed.Since I am still having dizzy spells sometimes, this thursday I'm going to go get a spinal tap to see if it is in my spine or not,so when I get the results back I will let you know as soon as possible.Again I'm sorry its been so long I will try to do alot more updates.Thanks for all you support it means alot to me.