About the study Vaccine For A Cure

 The vaccine is ONT-10 and it is given in combination with varlilumab. Varlilumab (does that sound like a type of yoga pants) is an antibody. The goal is that combination of the two drugs will activate my immune system to fight the cancer. The combination of the two drugs is a new phase 1b study and so far the dose and side effects have not been established. It is an open label study (i.e., I get the drugs that they say I get). There are no placebos or experimental manipulations except for the dosage. We all get the same great deal.

Three days before the start of the study:

Again I reported to the infusion center and this time there was no problem. I had an infusion of a small dose of Cytoxan (cyclophosphamide) to jumpstart the immune system response. It was not like serious chemo at all. I had a bit of nausea but nothing my regular anti-nausea drugs could not take care of. I had no loss of hair or anything drastic. It was given with a premed of Kytril and I drove myself home without a problem.

Three days later I was back at the hospital for day 1 of the trial.

Day 1

I saw the nurse practioner who checked me over and made sure that I was still exercising and eating properly.

I had 4 subcutaneous (under the skin) injections of the vaccine ONT-10 in the abdomen and legs and then vitals checked to make sure I did not have a reaction. My drug reactions are legendary (not a good thing) so a clean bill of health was a huge relief. I then trotted off down to the infusion center to get my varlilumab. The nurse came to do the infusion and I noticed she was wearing chemo gear. She laughed and said that she was just checking to see if I was paying attention because of course I was not getting chemo.

Except for the three tries for a vein, everything went smoothly enough. I had the infusion over 90 minutes and then had to have blood drawn from a different vein (two more sticks) for a pk (pharmacokinetics; how much of the drug is in my body). I was fine and drove myself home.

Day 8 and 15

For the next two weeks, I went and got my ONT-10 injections and then home. Still no side effects at all.

Day 22

The ONT-10 injections happened as usual. After that it was a trip to the infusion center for another dose of varlilumab. This was the same as Day 1. The infusion over 90 minutes and then a pk. Again, there was no need of a premed and no reaction.

Day 29

This was a fun (not) visit. It started off with 18 tubes of blood being drawn. Fortunately, the phlebotomist knew a thing or two and it only took one stick. After that, it was plain sailing. I had the four injections and went home.

I’m half way through the dose loading phase. I really hope it is working. I'm living a normal life. I have no pain and no side effects. I work 40 or more hours a week, exercise two hours a day, bake bread four times a week, read and do all the things wives, mothers and friends do.

 

 

 

 

 

 

Starting a new trial

My clinical trial with MLNo128 finally ended on December 23 with the scans showing disease progression. It was one of those drugs that was too toxic for me at the full dose but not effective enough at a reduced dose. I still have residual side effects even though I have been off the drug for over two months. My nails are still dry and brittle, my tummy trouble is not fully resolved and I itch all over, all night. My back looks like I have a serious case of the kinkies the way I have scratched myself. However, I had a good run in the world of clinical trials and metastases. I was on the drug for 32 weeks before progression and I still exercised for two hours a day, ate my vegan diet, slept as poorly as usual, did chores, watched movies, worked full time, learned something new every day (I am addicted to MOOCs) and was a mother and wife and friend.

I spent a few days in Florida at Islands of Adventure and Universal in Orlando and staying with dear friends on the beach. I went for long walks and ate great food and put my illness in a little box in the back of my mind for a little while.

The problem with clinical trials is there is no wiggle room. A scan scheduled just before holidays means exactly that. There is no postponing to a less-stressful week later and this scan day was a day that one wishes did not exist. Although I hadn’t had any pain, I had some feeling of things weren’t quite normal. Normal of course is a moving target when you have cancer and half of you hopes that this is just a different normal, but the sensible half of you knows that the results of the scan are not going to go your way.

 I had a complete melt-down at the doctor but had pulled up my big girl pants by the time I got home and cheerfully celebrated the holidays with my family, reserving tears and fears for the loneliest small hours of the night. We ate good food and played games and I took my usual thousands of photos while the washout period of four weeks began. It’s very scary to be told that all treatment will stop for four weeks before you can join the next clinical trial.

First stop was a liver biopsy. That was relatively painless and I arranged to donate tissue for research at the same time. Then came the blood work. They had to take so much blood that it had to be done on two different days. The first visit was 12 tubes of blood and a few days later I went back for another 16 tubes, an EKG and urinalysis. I was finally ready to have the infusion.

I got to the infusion center on the appointed day, exactly four weeks after my scan and the research coordinator caught me before I went in. I could not start the trial because my white blood cell count was too low. This has been an endless problem since I had my first round of chemo a decade ago. I was devastated. Not only did it mean I missed the start of the trial but now I had to have the scans repeated because I had missed the four week cut-off since my last scans. So I duly went and had more scans and breathed through the associated anxiety. As you can imagine, four weeks without treatment meant that my scans were not pretty. However, I swallowed hard and prepared myself for the new trial.

First step was I had to get my WBC count up. I did the right things and did what I was told. As insurance, I ran up 48 flights of stairs before my blood was drawn for a WBC count. Ha. The count was higher than it has been in a decade. Now it was way up and I could begin.

 

It's been a while

Clinical trial MLN0128

This update was really difficult to write but it turned out for the best because I ended this trial at exactly the right time to start the immunotherapy one. More on that later. This update is from the last blog to early December when things started to go wrong for me and MLN0128. To tell the truth, things had been going wrong for some time but this was an escalation of disaster.

When people talk about the roller coaster of stage IV, I don’t see it like that. I get the metaphor of the highs and lows but there is no thrill in the rapid decline that precedes the low. I think of it as more like a tsunami that has endless waves that keep pulling you deeper and deeper into destruction and with it are the homes and lives of loved ones destroyed by the pain of losing a mother or daughter or sister. I think this is hardest for the mothers who lose their daughters and are helpless to protect them from the onslaught.

The clinical trial required monthly visits to see the doctor or nurse practitioner and these events were always ones I would really rather miss. Every time I see the appointment reminder on my phone there is a big red “Cancel Appointment” button that I long to click. But I never clicked it and I went every four weeks as required by the clinical trial and would hand back the four pills (carefully counted by the pharmacist) and collect another 30-day supply of 60 pills. I also had a sheet with the exact times I took the pills every day and the glucometer with the readings of the twice-weekly finger prick results.

At my November visit, my drugs were delayed. Apparently, my liver enzymes were elevated. There were a bad few moments. My immediate thought was that liver metastases had progressed to a dangerous level, but the NP reassured me that it was probably “just” a side effect of the drug. An abnormal blood result is a huge palaver. Everything has to be checked against the protocol. It turned out the results were only a level 2 elevation so I was good to go with another month of drugs but needed to have blood drawn in two weeks to check. I am not sure but I think the fact that I had been trying to put some weight back on and consuming about 3000 calories a day might have had something to do with it. I decided to cut down on the 85% dark chocolate.

The doctor visits consume a huge chunk of the day. I had to fast (water only) before the blood draws and that is tough as only a caffeine addict would know.  I always think I should have a flashing light on my car to warn people when I haven’t had my caffeine. I have to leave an hour before the appointments to get there in time and have started to make a flask of green tea for these long days while I wait for the results of blood tests. On this cold November day, I felt like a construction worker sitting in the waiting room and drinking from a thermos cup, huddled in my polar bear hat.

While I was waiting, I talked to another patient who had to come back to get her prescription changed for her opioids because the prescription was for one month and it had only been four weeks since she had picked up her last prescription. She has Stage IV and is in constant pain. I just don’t understand the need for all this bureaucracy. Doctors constantly offer me Ativan and I decline. I never refill my prescription. I just ask for a new one about every 9 months or so, but ¼ of .5mg really works well for mild nausea.

While we were waiting, she told me her very sad story. Her husband was killed in a car crash seven years ago and she still felt her life was bereft of meaning. She and her husband were stopped at a stop street and the oncoming car with bald tires skidded on the icy road right into them. Her husband was killed instantly and she required hospitalization and surgeries. The driver of the car was in the country illegally and had no driver’s license or insurance. He was unhurt.

I went home exhausted and emotionally spent that day but ready to enjoy Thanksgiving break with two of my children who managed to make it home.

I watched one play video games. He has a wonderful way with words and amuses us immensely. He is also very sociable and goes out most evenings.

The other son is more serious. He has a wide general knowledge and it’s fun to ask him about things as you think of them. His ambition is to read the whole of Wikipedia but of course he can’t. He has still made huge inroads and read more than most with a deep understanding. He has an undergraduate science degree and a graduate computer science degree and is rapidly rising in the ranks at Google.

Whenever we have children home we like to go out and eat. I have a few favorites. I don’t make a big deal of whatever is available but some restaurants have nothing that I can eat. A clue is if you see the words deep fried at the top of the menu.

 We love to sit in the hot tub in the evenings and just talk. It’s a communal time where everyone shares what they did and what they hope for. The boys have a beer and conversation is animated.  

The days go so quickly now.

On Thanksgiving Day we went for a 5k run. There were over 8000 people there and it was chaotic. I don’t understand why it is so popular when it is so badly organized. It was thoroughly miserable and definitely tops my worse run experience ever and I have been on some pretty bad ones. It took 45 minutes to actually get to the start because they had no system. The sponsors were United Way which makes me think that if they can’t organize a simple 5k run then what can they organize? They are not on my current list of charities anyway but now they never will be. The highlight was getting home to soak in the hot tub for 20 minutes before I started cooking.

I did go back to have blood checked again two weeks later and everything was back to normal. And so the tide turns and takes a short break before the next wave hits.

 

Metaphor in Lord of the Rings

Update on clinical trial MLN0128

Cycle 7, week 4

I have been in the clinical trial for almost 8 months. I still feel fine with no new symptoms but my next scans are still just over 4 weeks away. The most bothersome side effect is the itching. I have a fine rash over most of my torso and it itches terribly at times. It is far worse than when I was on the 5 mg so I’m wondering if it has something to do with 4 mg being in the form of two capsules and 5 mg in the form of one capsule. I have a bit of diarrhea when I wake in the mornings but it is not like before. I also have occasional nausea. However, now that I take the drug at night, I take an Ativan and that sends me to sleep and I sleep through the nausea.  The mouth ulcers come and go as before. I still run for an average of 30 minutes a day and walk 50 – 60 miles a week. I still work and bake bread and record my life in photographs and video. I haven’t done any traveling in the last four weeks. I came back from NYC  with a terrible cold and it took weeks to recover.

Metaphor in Lord of the Rings.

Frodo: I wish none of this had happened.
Gandalf: So do all who live to see such times. But that is not for them to decide. All we have to decide is what to do with the time that is given to us.

As the weather turns colder, I am stuck exercising on the treadmill more and more. The treadmill is nicely placed in front of our large screen TV so this is an opportunity to revisit my favorite movies. Currently, I’m working my way through the LOTR trilogy for the many-ith time. At the end of Fellowship and the beginning off Two Towers is the battle of Gandalf and the Balrog, Durin’s Bane. As I watched it again, I was struck by the metaphor of cancer as Gandalf the Grey fought the Balrog.

Now, I have never liked the metaphor of cancer as a battle or fight. A battle implies that you have a chance of winning if you fight strategically. What we know, or more accurately, don’t know about cancer makes winning or losing arbitrary. My response to people who think they will win against cancer is, “Maybe you will and maybe you won’t.” You do not defeat cancer by force of will.

At the Bridge of Khazad-dum, Gandalf turned and faced the Balrog and refused to let it pass so that the others could escape. Gandalf broke the bridge and the Balrog fell. Gandalf then turned away from the Balrog and the falling bridge to flee with the others who were escaping. However, as the Balrog fell, it wrapped its whip around Gandalf’s legs and dragged him into the abyss. The two continued their battle until Gandalf killed the Balrog. However, the cost was the life of Gandalf the Grey. Gandalf returned briefly as Gandalf the White to complete his tasks.

As we face the diagnosis of cancer we turn and fight. We bear the beatings of surgery, radiation and chemo. Then finally we are done. We are exhausted and wounded and battle weary, but hopeful that is all we have to endure. We turn to flee back to our old lives. But we are suspended there at the end of the crumbling bridge in a timeless void. We have no idea if the whip of cancer will catch us again and pull us down into the abyss to continue the battle, knowing that if it does we must die. We can fight and take the lashes for a while and use the time to finish our quests but this will be our final battle. We will find incredible strength at times, but the old wounds will haunt us and eventually we have to confront the end. The Balrog dies when we die.  

 

 

 

Update clinical trial MLN0128

Cycle 7, week 4

Amazingly, I have been on this clinical trial for almost seven months. During that time, I have had three scans. The first scan after two months showed dramatic improvement, the second after four months showed stability and the third after six months again showed dramatic improvement. Of course, I don’t have information on how others are doing, but I’m told that my response has been outstanding. As researchers and biotech companies try to unlock the secrets of why some do very well, some stay stable and some just don’t respond at all to the new drugs, I am fortunate to be part of this and I don’t take the science or the luck for granted.

There have been definite ups and downs. The first three months were relatively easy. My biggest challenge was facing down the mouth ulcers that covered the inside of my mouth, too many to count. Valtrex  (a drug I have taken for cold sores) and capsaicin (the chemical that gives hot peppers their burn), got me through that stage. I found the best way to numb my mouth was to rinse it with very hot salsa so that the capsaicin made every nerve ending scream while I white-knuckled the edge of the sink and let the pain wash over me. The nausea and occasional vomiting were controlled with hefty prescription drugs.

At about the three-month point, I started getting diarrhea. This put a definite damper on my enthusiasm for the drug. At first, the diarrhea was controlled with regular four-hourly doses of Tincture of Opium. Despite the romantic-sounding name, it is the worst tasting medicine you can imagine and has none of the good effects. I kept taking it every four hours so that I could go to work, run, eat, and live. Gradually, however, I would have to plan my day more carefully. It was good for four hours and maybe a second dose would work for another three. I began to arrange my schedule around the opium like a dyed-in-the-wool addict. The nurse suggested I halve the clinical trial drug for a while. I refused. I am not used to giving in to discomfort and inconvenience.

Finally, however, I skipped my last dose of the clinical trial drug at the end of the sixth month. My weight had fallen to just over 100 lbs. on my 5’6” frame. I could barely walk. I could not eat and I was so dehydrated that my eyes were dull. That is not to say that I gave up running. Of course not. Every day, I set off for my five miles. I never made it anymore without stopping on the side of the road to rest. I continue to be surprised that no one stopped to ask if I was all right. I longed for a drink of water, but forgot to take it with me because my decision-making was so clouded.

At the six-month check the oncologist did not give me a choice anymore. I was to stop the drug for at least a week until I felt a little better. My relief at having the decision taken from me finally melted my resolve to stick it out and I could not stop the hot tears. I ended up stopping the drug for two weeks and the diarrhea stopped. I got my appetite back and managed to run five miles without stopping again.

 

 

I am now back on the drug at the lower dose of 4 mg instead of 5mg. I desperately hope that it continues to work but I also know that there were serious QOL issues at the higher dose. I have no pain and no symptoms but I’m not under any illusion that means I am fine. 

I have had seven months more of life that I might not have had. I have watched winter turn to spring then to summer and now to fall. I can measure what I have done in actions. I have given academic presentations and taught my students and listened to them and taken them out to eat. I have helped them write scholarships and graduate school applications. I have written letters of recommendation.  I have fought with the chair of the department when he was wrong. In the last seven months, I have taken trips to Salt Lake City, Omaha, Tampa, St. Pete’s Beach, Las Vegas, San Francisco, New York City (twice), San Diego, Orlando, and Anaheim and  have attended 10 conventions. In seven months I have run and/or walked over 1400 miles.

 

 

However, my life has been so much more than a series of actions. I have worked and been a responsive and involved wife and mother and professor. I have cooked and cleaned and played with the dog. I have found my community of friends online who I genuinely love and respect. I have been a supportive friend because I still can be one. I have still been able to give more than I need from others. And so it is onward and upward.

 

 

 

 

 

Profile of a woman dying of breast cancer

·         I am every woman. There are parts of me that are you.
·         I love my family more than anything and they love me. Or so they say.
·         I am neither young nor old. I am unlikely to ever see retirement age and will never use my retirement savings.
·         I am neither rich nor poor, but closer to rich than poor due to a lifetime of working and saving.
·         I am 5 ft. 6 in. and have never weighed more than 115 lbs. except when I was pregnant. After each pregnancy I was back at 115 lbs. by my 6-week checkup.
·         I had four normal pregnancies and gave natural birth to four healthy children. I breastfed each baby for 18 months.
·         I have never smoked and drank very little alcohol (about a glass a month) and none in the last two decades.
·         I never went on the birth control pill because there was a study published in the 1980s that it was associated with breast cancer. See above for four children.
·         I have been a vegetarian almost all my life and a vegan for the last decade.
·         I have run and walked 50 – 60 miles a week almost every week since I was in high school, even up to the day my babies were born and a few days later.
·         Most of my shoes are running shoes.
·         I floss my teeth twice a day.
·         I am a terrible dancer and cannot sing in tune.
·         I have no sense of direction and will get lost anywhere. Getting lost is my special skill.
·         I cannot draw and am in awe of all who can.
·         I’m allergic to anti-cholinergics and dairy.
·         I have been prepared to die for my beliefs.
·         I care very much for the mentally ill. I give a dollar to all homeless people who ask. I keep a stack of dollar bills for this purpose.
·         My students call me the department mom.
·         I am a card carrying member of the ACLU. Although I don’t support all their causes, I feel that someone should.
·         I can hold very hot things and I stop watches that I try to wear.
·         I have hundreds of thousands of photographs of my family and trips.
·         I have had four different first languages. I learn and forget languages very easily.
·         I have traveled a lot.
·         I have two master’s degrees and a PhD. I am a scientist.
·         I have had three completely different careers.
·         I love JK Rowling, Jane Austen and Alexander McCall Smith.
·         I read about one book a week.
·         I covered up my radiation tattoos with tattoos of a four-leaf clover (my four children), a stylized deathly hallows, an owl and a dragon.
·         I cry easily when you tell me a sad story. I faint when I see someone in pain.
·         I hate scary movies.
·         I am very loyal and find betrayal unforgivable. I can hold a grudge for a long time.
·         I laugh often and loudly to the embarrassment of my children.
·         I am dying even though I did everything I knew to prevent this disease and then its recurrence.

My wish list for the NIH

Over the past four decades I have seen a lot of really unhelpful research on breast cancer. And let’s face it, we really have not got very far. Recently, I have been asking why grant reviewers have not demanded more useful research, only to find that I am late to the party.

There was an interesting article at http://www.wnyc.org/story/when-patients-set-sciences-research-agenda-who-loses/ in which patients set the agenda for breast cancer research instead of the individual researcher with an idea. Yes.

Here is MY wish list for the battle. And it is a battle. However, when I die of this disease, please do not say that I lost my battle. Every time a woman or man dies of breast cancer, we all lose a battle. It is only my list but we are in this together and hiding behind pink ribbons does not stop the wives, mothers, sisters and daughters, husbands, fathers, brothers and sons from being mowed down.

1.       Funding. The NIH could open a fund for breast cancer research and everyone who wants to donate could donate directly. The NIH already hires staff to oversee grant funding so they will have no incentive to raise funds for the sole purpose of maintaining their organization. Let’s boycott pinkwash. They had a chance but used our money to tie pretty pink ribbons in the name of awareness while women and men died.

2.       Prevention. Prevention would be ideal. We know that longevity runs in families. What is it about some people that makes them less susceptible to cancer? What if we study the healthy to find out why their cells never turn cancerous? How can we use that information to prevent our errant cells from turning on us? In fact, many of us are our own labs. If breast cancer only develops in one breast, what caused the mutation in DNA in that breast and not the other?

3.       Treatment. Why is the current treatment not working very well? In fact, how well is it working? We have not made a lot of progress in terms of survival and it would be good to know why.

4.       Metastases. Why do some cancers progress and others don’t? Let’s eliminate talk of that five-year survival window. Many of us easily make it. It is meaningless and artificial. Let’s study every patient from diagnosis to death and record recurrence if and when it happens. Let’s examine what is working for long-term survivors so that every patient can be a long-term survivor.

5.       Correlations. A correlation is an association between two events such as eating red meat and breast cancer (unproven) and is reported using Relative Risk (RR). Correlation does not mean causation. Some studies showed an association, but when you combine all the data from all the studies, the effect often disappears. One of the most robust associations is between smoking and lung cancer. If you smoke, you are more likely to get lung cancer than if you do not. However, not all who get lung cancer smoke and not all smokers get lung cancer. In fact, the lifetime chance of getting lung cancer if you smoke is only between 15 and 25% (depends on your source) of all smokers. Correlation has a number of flaws so let’s see no more correlations. It is especially important to disregard correlations that are drawn from a patient’s memory. A study from 1993 described how patients’ memories of what they ate was altered after the diagnosis of breast cancer. In an earlier survey they had described their diets. After the breast cancer diagnosis, their memory of what they had eaten included more fat than the original survey. In other words, the diagnosis changed their memories. There is a good explanation by Charles Wheelan at http://thegovlab.org/garbage-in-garbage-out-or-how-to-lie-with-bad-data/ If you are still not convinced that correlations are not helpful, you can find some really funny ones at http://fatchicksings.com/2014/05/12/does-eating-margarine-cause-divorce-correlation-is-not-causation/

6.       Central database. The power of 21^st Century computing is not being exploited. The entire genome (all the genes of a cell) of all breast cancer patients, their diet and exercise habits as well as their treatment, side effects and recurrence could be kept in a central store and computers can sift out the common elements. I am now in a clinical trial and the trial sponsors  demand a lot of my blood. The results are for their clinical trial alone. Now, imagine if that amount of data could be pooled for every patient.  Data could be input by health care workers and patients. We could sort out common side effects that some doctors refuse to acknowledge even exist.

7.       Grants would be prioritized so that applied research now gets top priority. Basic research has led the field and has resulted in a theoretical understanding of breast cancer, but now we have reached a point where the research must be applied to saving lives. We cannot afford to keep waiting for the theory to lead to changes in far future treatments. We need treatments now, and we need it from researchers as well as biotech companies.

8.       Stop funding unhelpful research. If the research does not save lives, or it requires leaps in logic, or is so theoretical that it cannot be implemented, it is not helpful. Every study needs to answer the question: Why is this important? Let’s move on from the research flavor of the month.

9.       Every research trial could be registered with the NIH before it even starts, and not only the ones funded by the NIH. That way, if there are a thousand studies on say, the use of soy, but only five showed significant effects then we can examine the effects of random chance.   According to Charles Wheelen, some journals already require this. http://thegovlab.org/garbage-in-garbage-out-or-how-to-lie-with-bad-data/

10.   One more selfish thing. The clinical trial that I am on has a side effect of diarrhea. Chemo left me unable to tolerate anti-cholinergics. All that is left for me is the absurdly disgusting tincture of opium. Why am I controlling side effects with a drug that is thousands of years old? I’m not much of a whiner. I get up in the morning, run, do chores, be a wife and mother and go to work no matter how sick I feel, but tincture of opium brings out the 2-year-old in me.

·         2-year-old me: I don’t want to take it. It tastes terrible.

·         Logical me: You have to take it to stop the diarrhea.

·         2-year-old me: But the taste does not go away for a long time.

·         Logical me: But the diarrhea will not stop if you don’t take it.

·         2-year-old me: What’s the point? I’ll just have to take it again in 4 hours

·         Logical me: Your diarrhea will be more-or-less controlled for 4 hours

·         2-year-old me: But it won’t go away

·         Logical me: It will get worse if you don’t take the drug

·         2-year-old me: No, maybe it will stop now

·         Logical me: You know it won’t.

And you won’t believe how long this can go on.