Clinical Trial Update

About three weeks ago, I had my first immunological treatment with Tecentriq (https://www.gene.com/patients/medicines/tecentriq).  About the only side effect that might be related to the drug has been lower leg cramps.  I had them most nights during the first week, but they have subsided. 

This week I got the first dose of the experimental drug GCD-0919.  Because both drugs are supposed to activate the immune system, the possibility of side effects is increased.  So far it seems like I have less stamina than I’ve had recently.  For example, I was exhausted after lunch by unloading the dishwasher and putting the dishes away, and I had to sit down and recuperate.

The new drug is a given in capsules which is a new type of cancer treatment for me.  I take 12 capsules, twice a day, twelve hours apart.  I came home from my first dosing with 24 bottles of 24 pills each.  One bottle per day.  I can’t eat during a three-hour window around taking the pills (2 hours before and one hour after).  So going forward, I’ll get an infusion of Tecentriq every three weeks and take the GCD-0919 every day until the side effects become intolerable or dangerous or my disease progresses.  The cancer adventure continues.

David

PS  For those who might be interested.  I'm working on a post or perhaps a series of posts about clinical trials.  What they are.  Where to find them.  How they are conducted.  Etc.  Watch this space.

PS2  Twelve pills sounds like a lot, but they are small and easy to take.  I take them four at a time, so it's only three swallows.  Here's what they look like in a tablespoon.

 

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.

Jana: CML Update David: Clinical Trial

Jana

Jana had a blood test in September for evidence of CML that showed that she still shows no evidence of the disease.  It’s been about 2.5 years since she last showed any sign of the disease.  She feels good all the time and is active in a group that sings at assisted living centers and in volunteering at the Eastern Star Masonic Retirement Center where her mother lived before her death. 

Yesterday I read a summary of a new research study that produced this Take Home Message:

This study was a long-term follow up (median, 77 months) of a previously reported study in which 100 patients with CML with undetectable minimal residual disease (MRD) after 2 years of therapy had Gleevec discontinued and were followed.  Only 61 of 100 patients developed molecular recurrence during the prolonged follow-up.  The 5-year molecular relapse–free survival was 38%.  Of the 61 patients who relapsed, 57 restarted therapy.  As many as 97% of retreated patients achieved a second undetectable MRD status.

We find these to be very hopeful findings.

David

I completed my 36 cardiac rehabilitation sessions last month.  I grew somewhat stronger over the course of treatment, but not as much as I would have liked.  I am trying to exercise at home and have been somewhat successful at walking on the treadmill regularly; however, I still become fatigued easily.  A trip to the grocery store can wear me out.  On the other hand, a couple of weeks ago I drove us through the mountains on a 175 mile trip to see the yellow aspens.

The big news is that I’m being considered for a clinical trial at the U of Colorado Hospital.  This is exciting because the trial is testing two immunological cancer treatments.  The drugs are designed to remove the camouflage (antigens PD-L1 and IDO) from my cancer cells so my T-cells can kill them.  To be included the patient had to have tumors that express one and/or both of the antigens.  I learned yesterday that my cells express PD-l1.  I have a start-of-the trial exam, lab work, and CT on Thursday.

After the trial gets underway, I’ll add a detailed post about what the trial is supposed to do and how the treatment is going. 

David

Cancer Immunotherapy

My cancer goal these days is to live long enough to received an immunological cancer treatment.  Here is a link to an excellent special report from the NY Times about the hopeful field of cancer immunology for those who would like to know more.

Talking with Doctors at the End of Life

Here is an interesting article about the difficult communication between doctors, patients, and family at the end of life.  I believe my oncologist and his nurse practitioner will be straightforward with when the time comes because they know me well enough to know that I want their prognosis and will not overreact.

The Boxer

To all of you cancer survivors out there.

Yesterday, the lyrics of part of Simon and Garfunkel's "The Boxer" came to me.

In the clearing stands a boxer

And a fighter by his trade

And he carries the reminders

Of every glove that laid him down

And cut him till he cried out

In his anger and his shame

"I am leaving, I am leaving"

But the fighter still remains

After my rounds with cisplatin, my chemo has never been awful. I've never lost my hair or suffered from uncontrollable nausea. However, there have been times in my 50-odd round of chemo when I thought, "I'm not going through this again. I'm leaving." but I remain. Here's to all of you who have remained until it was over.

David 

PS I'm not leaving, but today I start a one month chemo break, a sort of "leave of absence."

July 1