Flare phenomenon

The oncologist saw me after my CT scan and was quite hopping with excitement. The clinical trial was going well. The trial drug was melting the liver tumors like water melted the wicked witch of the east. But (there is always a but in this teeter-totter world of stage IV) I still had to have tumor markers drawn and the bone scan.

The tumor markers had not gone down. They had actually crept up. Deep breaths. I repeated my mantra, “Don’t look for trouble. Don’t look for trouble. The oncologist always says scans trump markers.”

Then the bone scan results were released. I was like, “You can’t be serious.” It seems my skeleton decided to come out of hibernation and light up like Times Square at New Year.

To preempt my freak out, the oncologist had added a note to the start of the report. She called it a flare phenomenon. The bone activity was sclerosis – adding new bone. The new bone was even in my spine where a prior MRI had shown was not mets but a bulging disc in my lower back. Like every freaked out patient, I went straight to Google for more information. However, finding useful information on a flare phenomenon was like searching in the early days before Google. You know what I mean. (Life before Google: I wonder….. Too bad.)

So I just went with it and tried to compare it to something that I do understand: extinction burst. When you have been reinforcing a rat with fruit loops for bar-pressing and suddenly you stop the reinforcement, the rat presses the bar frantically for a few minutes, until it is clear that there is not going to be any reinforcement. Human adults and children do this too. Often parents are told to ignore a child’s behavior and it will stop. (I’m talking about selected behavior here, like whining). The parent will come back a week later and complain that the whining did not stop. It actually got worse. That would be extinction burst and you have to hold on tight to weather that onslaught. Think of what adults do when they put money in the vending machine and they get nothing back.

I realize the leaps in logic I am making here, but it is not meant to be taken literally. It’s a metaphor for MLN0128 – 1, cancer - 0.

The most unsettling part is the warning the oncologist wrote at the bottom of the note. I am to monitor how I feel and report any deterioration in my condition.  I mean, who has time for that? I have a massage scheduled, movies with my children on Sunday and then I have to get ahead with my work because I’m going to a convention next week-end. Seriously though, the vagaries of monitoring pain is a topic for another post.

Reading Comics

 Have you read a comic today?

To say that I love comics is understating my passion for words and pictures. Comics are my refuge. After a good oncologist visit, I will celebrate with a new comic. After a bad visit (more and more lately), I’ll treat myself to two comics. I read them to get going in the morning and last thing at night. I read them while I’m waiting for the kettle to boil, the doctor to get to me, the nurse with my shots, and my husband and children to get ready.

In comic land, I can escape to the world I would choose to live in. If good does not trump evil, I am not interested. I choose a just world with strong characters, sharp wits and a fighting spirit wrapped around a steel moral core. For a few stolen minutes, I firmly shut the door on the evil disease that defines so many things about me and sucks so much comic-reading time.

There is something so in-your-face about the raw emotions captured in a comic. I love the way an evil smirk curls the lips upward and inward, the color of an angry face, the evasive look of a lie.

Sometimes, I get to escape to live in comics for a few days at a convention. I do research on comics so I have an excuse to talk comics wherever I go. At conventions, I am in character if I can get away with it. The one who is dressed as a Star Trek science officer, a character from Harry Potter or Thor’s mother, Frigga – that would be me. My son described three kinds of nerds: There are nerds who go to cons, super nerds who wear nerdy t-shirts and then there are the eccentric nerds who don costumes. Welcome to my eccentricity.

At conventions, I will stand in line with a team of comic characters and talk about web comics and graphic novels and no one cares about my tumor markers or next scan. No one asks me how I am in that meaningful way, and for a short while I can forget that my body is disintegrating under my suit of armor. We talk about the next panel and the last one and how tiring but fun this is. We browse at the merchant booths and admire the artists. We discuss zombie tales with authors and find out which artists are just jerks and which are so nice that we want to just hand over our credit cards to them.

Most of all, I love to learn new stuff. I find out how to model resin and clay into superheroes or villains, how to make a foam Godzilla or how Gargoyles was pitched to Disney. I pretend that I will be able to use this knowledge for a long time.

In the cancer universe, I huddle miserably as the oncologist wraps me in chains with words like clinical trials and disease progression. In the comic multiverse, there are no stupid rules. Facing evil is a choice.

Shall we read a comic today?

Breaking the chain

To all who never had the father they deserved, you will recognize this story. The details may differ, but the hurt does not.

Like a familiar smell activates old memories, so can other visceral responses.

Nausea and pain are old enemies. The main difference is the nausea and pain I have today are a result of the disease and the drugs whereas the nausea and pain of my childhood were a consequence of a father who was an angry alcoholic. Fathers now seem so different from when I was a child. It’s not as though all fathers in the sixties and seventies were abusive. On the contrary, many of my friends had fathers who were very loving and involved in their lives. However, living in a British colony in Africa seemed to offer a protected environment for violent fathers at that time. There was a code of complicity among the ex-pats.

When I was about 13, the health department nurse played a surprise visit to our school. She was checking our smallpox vaccination scars on our arms. I claimed that I had no scar. I would not remove my sweater to show my torn shirt and bruises. She contacted my mother who supported the lie. We all kept the code of silence. It was not that my mother condoned the violence. She gave regular spankings but never left more than a red mark. When he would start to hit, she would sob and plead with him to stop. But when the anger took over and the alcohol made it burn too wildly, then he had to hit and hit until the anger burned out.

There is a scene in Mommy Dearest when the child is being hit with a coat hanger. I lived this scene with Daddy dearest and this scene in the movie is exaggerated.  The coat hanger breaks much more quickly in real life.

 Although I call the only parents I knew my mother and my father, they were not my biological parents. I was adopted when I was about three years old, along with my baby sister. I had been living in an orphanage after my biological mother abandoned us. My biological father could not raise two small children alone so we become wards of the state. We were adopted by relatives who became my parents. In exchange for a roof over my head and food on the table, I owed total gratitude. Implicit in the total gratitude was quiet acceptance.  

The beatings were unpredictable which was why I often woke with a knot in my gut and why I dreaded weekends. I really would like to say that I defiantly stood up to him when he punched me in the face or hit me with whatever was handy. I did not. I cowered and wished him dead. The closest I came to defiance was when I planned to run away with the circus.

I was about 11 when the circus came to our sleepy village. They stayed a few weeks to make some repairs and my brother, sister and I would walk down to the fields where they camped. When they were ready to leave, I planned to leave with them. I was going to be a trapeze artist. My plan was foiled when my brother told my mother. She dealt with it by forbidding us to visit the circus folk again. When I think about this as an adult, I am sickened by the idea of a group of adults conspiring to help an 11 year old run away. I doubt a trapeze artist was their entire plan for me.

Looking back, I understand that this man only knew violence. His own childhood had been wretched and he never even graduated from high school. The beatings had been passed down for generations. He never hit my mother and I don’t think he realized that he had crossed the line from discipline to abuse. Even sober he never had a kind word for me. I’m not sure he even knew any.

I have had more opportunities. I have never raised my hand to another human being, and would never dream of hitting a child. At some point, we can break the chain of violence.

 

Talking about side-effects

The list of possible side effects on the consent was long. The one that I focused on was vomiting. Vomiting from chemo was very familiar and the most disruptive in every way. Although the oncologist reassured me that modern drugs hold it in check, Zofran only took the edge off for me when I went through the first round eight years ago. However, this time Zofran is not even a consideration as it is now not even allowed with the new protocol. Until I had chemo, I would puzzle about why people had carpets on the bathroom floor. Lying on the floor curled up on a tiny bathroom mat after chemo, I finally understood. Without the strength to do more than lift my head to vomit again, any small comfort would have felt like luxury. Fortunately, that particular side effect has thus far not been one of my obsessions this round. Like many things about cancer, I worried needlessly.

The side effects that I have experienced seem to be random and I think fall into two categories:   Things that would have happened anyway and things that are definitely due to the drug.

For example, my annoying cough is listed as a side-effect possibility. But then my son came home for break with a soul racking cough that makes his ribs rattle. If my cough goes away it is an infection, if it does not then it’s the drug. It’s not mets to the lungs. There is a certain reassurance to frequent scans.

The drug has resulted in abnormal blood results. It is definitely having an effect on the liver and the numbers   get more out of whack every time I have them taken – i.e., every two weeks. No one even seems mildly surprised.

The worst thing about the random bouts of nausea is that they are totally unpredictable. I can be on a run, watching TV or at a lab meeting and it hits with no warning. The nausea started the day I started the drug and there is not a day that goes by when I am not sidelined for at least a few minutes while I try to get the gastric churning under control. It is not usually outrageous. Sometimes I can distract myself but at other times I just have to sit very quietly and let it wash over me and wait until it passes.

Mouth ulcers have been wicked. They peaked about four weeks after starting the drug when the problem escalated from one or two at a time to feeling as though a mouth ulcer volcano had erupted into my mouth and left huge puddles of white larva all over the inside of my mouth. I had more white than pink on my gums. Needless to say, the pain was debilitating. The nurse wrote a prescription for a local anesthetic which I was to mix with Maalox and swish around my mouth. The pharmacist warned me not to eat after using it as I could choke or bite my tongue or cheek. This advice seemed to contradict the point of using it. I tried using a q-tip to dot the ulcers but there were too many. It was time to face my demons.  I was going to burn off the pain with a nice hot salsa and let the capsaicin do the work of numbing my mouth before I ate. The pain from those chilies was exquisite. I put the salsa in my mouth and clamped my jaw while the pain washed over me and tears fell in torrents. After a few minutes, I could eat.

The good news was that I did find a long-term solution by accident. I sometimes get cold sores (herpes on the lips) and take Valtrex as soon as I feel one starting. Valtrex completely eradicated the mouth ulcers as well as the cold sores. After two doses, I could see the mouth ulcers visibly retreating. It was like time-lapse photography. Every time I checked my mouth, they had shrunk a bit more. Within a few days there was nothing left of them. My oncologist was amazed and is going to bear it in mind.

I have not solved the vexing diarrhea problem. This is especially disconcerting when I go running. I’m experimenting with diet (not eating) but haven’t got to a satisfactory place yet.

Fatigue is also a problem noted by many on this drug. I haven’t let myself take the time. I have been to five conferences in five different cities over the past six weeks. I also have another planned this weekend. My undergraduate students, thirty years younger than me, complain that just one conference is exhausting by the end of the second day. I don’t think they feel my urgency.

The absolute worst thing is that one never knows if the drug is working or you are suffering needlessly. A scan after two months showed that the two visible tumors on the liver has shrunk to 50% of the size they were. So I keep on and plan the next two months of my life living furiously. Scan, plan and repeat.

 

MLN0128 clinical trial

 

 

I have been fortunate to be able to join two clinical trials with this disease. The first one was 9 years ago when I joined a phase 3, dose-dense clinical trial. Phase 3 means that was randomly assigned to a group. The arm I was assigned to was IV Cytoxan and Adriamycin every two weeks (with Filgrastim for neutropenia in-between) for 12 weeks followed   by 6 weekly doses of Taxol.

When metastases was diagnosed after 8 years NED, I was taking the AI, Femara as well as Prolia for my bones. The treatment now notched up to Aromasin (exemestane), Faslodex and Xgeva. After 11 months on that regimen, a scan showed mets to the liver- four spots.

My treatment choice was a standard treatment or a clinical trial. I chose a clinical trial. I am a scientist. That was not even a decision that I needed time to think about.

The clinical trial is phase 1 b. This is the scary phase of a drug that is not yet FDA approved and even the dosage is not completely standardized. Phase 1 also means that I was not randomly assigned into a group, but openly assigned. My group is Faslodex monthly shots and 5 mg of the drug, MLN0128 every day. The drug is a TORC1/2 kinase inhibitor. It has been shown to work in the lab by inhibiting cancer growth in a number of mutations.

The study protocol calls for following 126 women with advanced breast cancer for as long as the drug works,  with follow ups after you stop taking the drug for any reason. Of course, if the cancer shows any progression while on the drug, you are off the clinical trial.

After signing all the consents I was ready to go.   Well, not quite. On day one I went for a consultation to see if I was  fit enough for the clinical trial. I was. I signed. I then had to wait out two weeks in the wash-out period when I was not allowed any drugs. Two weeks later I went for my first round of treatment. But first I had to sign the updated protocol because of minor changes to the procedure and a brand new list of possible side effects. That got my attention. The side effects deserve their own little celebration so I will discuss them later.

 

The protocol is as follows:

Every month I continue with the Faslodex (two large intramuscular shots in the rear) and Xgeva (one small burning shot into the fat of the stomach). I no longer take the Aromasin but instead take MLN0128 every morning at about the same time of day. Every two weeks it was back to the hospital to be evaluated by a doctor or nurse, have EKGs done and have more blood drawn.

As for the procedure:

Every morning the first thing that I do is prick my finger to test my blood sugar. I am not allowed anything to eat  or drink for at least eight hours before that – besides plain water. That finger prick procedure took some getting used to. I am not sure that the research coordinator explained it clearly. The next time I went on a visit I made sure that I spoke to a phlebotomist who has diabetes and she is a finger-pricking expert. I don’t know if I have had, or really even want enough practice to be an expert, but I have definitely improved and seldom have to prick more than once anymore.

The drug is to be taken with food. And lots of water. I think that is an effort to reduce nausea. If it is, it does not work for me.

The long list of side effects were given in order of most to least common.

 

My every day...

I am a list person. I feel sure that a day will not exist if I don't have a list of things to do. A sense of purpose is critical to our mental health and mine is documented.

My day begins with a glucose test. This is part of the clinical trial requirements for MLN0128. I  never imagined that I would prick my finger every single day, but then again there are many things that I now do that I never imagined that I would. I can only have my green tea after the blood has flowed. One tea and one coffee follow in quick succession and then it's a five mile run/walk while listening to an audible book. I exercise every single day, walking and running 50 - 60 miles a week.

Home for breakfast which is a bunch of healthy stuff thrown into the blender with frozen fruit and vegetables. I sip that while I answer email and get some writing done. Even though I am technically on break, there is always work to do for faculty. I take a break from my writing to clean up a little, jump on the treadmill while I catch an episode of Star Trek, take another shower and then think  about making dinner.

After dinner, I settle in to do some studying. I love to learn new things - the curse of curiosity.

Two children call and I sort out their minor crises.

I fall into bed exhausted every night. I know that my life is not nearly  as chaotic and unpredictable as many out there, but I still feel totally overwhelmed by my diagnosis. I have played by the rules my entire life and still I drew the short straw in longevity. There are many who would feel grateful for 75% of their predicted lifespan, but I cannot help feeling cheated.