October 27, 2016

Infusion Chair Replaces Chemo Chair



I'm writing this post as I receive my first infusion in a clinical trial.  I used to write about being in the chemo chair, but the drug I'm getting today is an immunological drug, not chemotherapy.  Chemotherapy drugs kill cells that are rapidly dividing whether or not they are cancerous.  The new immunological drugs are more specific in the cells they kill, and they kill by activating the immune system.

One part of the immune system consists of antigens and antibodies.  Antigens are molecules on the surface of a cells.  The immune system knows which antigens are normally expressed on various types of normal cells, so it does not react to a normal cell.  However, antigens that are not part of the normal repertoire are recognized as foreign and attacked.  Some cancer cells are so damaged that they express proteins that are recognized as abnormal, and are killed by the immune.  The thinking is that our bodies are constantly identifying such mutated cells and killing them.  However, some cancer cells express antigens that allow the cells to hide from the immune system.

One of those antigens is the PD-L1 protein.  PD stands for programmed death (apoptosis), a process that cells use to commit suicide.  When a T-cell sidles up to a cancer cell expressing PD-L1, the protein tells the T-cell, “Hey partner, I may look like I am broken and need to be killed, but I'm really OK.”  The T-cell says, “OK, my mistake,” and goes on to other cells without initiating programmed death.  PD-L1 thus provides camouflage for the cancer cell.

My drug, called Tecentriq, is a lab-developed monoclonal antibody that attaches to the PD-L1 protein masking it from the T-cell thereby allowing the T-cell to initiate programmed death.  To be admitted to the clinical trial, I had to have a biopsy of my tumors to see if I express PD-L1 which I do, so I am hopeful that Tecentriq will mask the protein and kill the mesothelioma cells.  Tecentriq has been approved for bladder and urethral cancer, but there is no guarantee that it will work with mesothelioma.  Another well-known immunological is Ketruda, the monoclonal antibody that helped cure President Carters melanoma.

Tecentriq is given every three weeks, but I'll come in to the clinical trial center each week at first to see how I am doing.  After the first three weeks, I will begin getting another monoclonal antibody drug as well; however, it works on another protein that is important to cell functioning.  The basic purpose of the study is to see how well the experimental drug works in combination with Tecentriq.  I'll write more about the experimental drug when I begin getting it. 

Over the past six years, I have never been anxious about any aspect of my cancer treatment; however, on my way over for my prescreening visit for the trial, I realized that I was anxious.  I think the anxiety comes from concern about the treatments on my weakened body.  I believe 58 prior infusions have damaged my body to a certain extent.  Will the new drugs exact a toll? 

There is a concern that the PD-L1 protein is involved with human development.  The DNA in every cell in the body contains all of our genes.  The differentiation of cells into heart cells, lung cells, etc. involves turning different genes on or off shaping the cells to do their job in the body.  PD-L1 may be used in development to signal to the immune system that even though a cell looks abnormal it is a normal cell for a certain type of tissue.  Something I don’t understand is whether mature differentiated cell still express PD-L1.  Will the Tecentriq unmask PD-L1 expressing normal cells and allow them to be killed like the cancer cells?  It may be that some of the possible side effects of the drug result from such action.  However, I read articles and drug package inserts online, and the drug seems generally to be tolerated well, and I will be under close scrutiny while in the trial.  I feel better about the risk now, although there is always a risk in a clinical trial.
 
My infusion is over for today, and all appears to have gone well.  Now all I have to do is hang around for checks of vital signs and a blood draw to measure the concentration of the drug in my blood.  Unfortunately, the nurse will have to draw the blood from a vein because the drug went in through my port and might contaminate the blood draw.

More to follow when I get the other drug or if anything of note happens. 

David

PS it is now nine hours later, and I have had no noticeable reaction to the infusion.  So far so good.

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