Touch and Go and Travel Resources

 

 For my October visit to Philly, I will essentially be doing a touch and go. I will fly in one afternoon, have my appointment and get my next 28 doses of Verzenio the next day, and then fly out the next morning. I'm thankful for Alaska Airlines and Atmos Rewards as their rewards program have pulled us through some of these flights so far.

 I wanted to share the many resources offered to me as someone who is being treated for cancer in hopes that it may help you or someone you know, if you happen to be in this less than ideal situation:

https://angelflightwest.org/ -  Serving Alaska, Hawaii, Washington, Idaho, Montana, Wyoming, Colorado, Utah, Arizona, California, Nevada, and Oregon.

https://angelflighteast.org/ - All other states

https://www.mercymedical.org/

https://www.footprintsflights.org/

https://www.cancer.org/support-programs-and-services/patient-lodging.html - Hope Lodges in various areas and a discount with Extended Stay America

https://www.headstrong.org/ - Another place available in Philadelphia

https://www.nationalbreastcancer.org/nbcf-programs/hope-kit/ - Free to send to someone you know with cancer - Includes various items such as Fuzzy socks, Tumbler, Tea, Clean beauty product, Unscented lotion, Lip balm, Hard candy, HOPE journal & pen, Inspirational bracelet, Educational resources, Encouragement card. THE GIFT OF HOPE

 If you're cross country like me, Angel Flight West and Angel Flight East cannot combine to get you there. I tried. :)

Pill Fatigue

 I have 3 clinical research prescribed pills at 8 am and 8 pm. I have 12 other prescription medications, 3 of which are eye drops. I take 34 over the counter medications or supplements to manage the side effects of my prescription medications, with 2 of those being eye drops. 

 That is a total of 52 medications. A. Day. It’s a part time job just getting those down the hatch. 

 I have to put something in my stomach before I can take many of these meds and am finding myself less and less hungry each day. It appears I’m tolerating the Verzenio well. Imodium is my friend but not being needed often. Juven is still a great addition, in my opinion.

 Another day down. Really hoping to get my appointments for my ABBY trial for October-December tomorrow. 🤞🏻

Positive Energy

 

There's no place like home and my Verzenio regimen

  Back home with my two best guys. 

  Dogs make everything better.

 My medication regimen is taking 150 mg Verzenio, twice daily, exactly 12 hours apart. There is a +/- 1 hour window to take the medication or I have to skip it for that dose. I have to keep a log of when it was taken and any side effects that I experienced. I have specific parameters for temperature and GI issues to call the UPenn oncologist to get further advice as a dose adjustment can be made if I am not tolerating it well. The #1 side effect?

  I was prescribed the following medications to help manage these symptoms, in order of escalation if needed:

• Imodium (Loperimide)
• Treats acute and chronic diarrhea
• Side effects of constipation, dizziness, and mild stomach discomfort (concern for addiction due to opioid)
• Mechanism of action - An opioid receptor agonist that attaches to and activates opioid receptors in your brain and body to provide pain relief, relaxation, or other effects such as reducing the movement of fluids and food through your digestive tract and helping the intestines absorb more water and salts due to diarrhea
• Diphenoxylate-Atropine (Lotomil)
• Treats severe diarrhea
• Side effects of dry mouth, headache, dizziness, drowsiness, and constipation
• Mechanism of action
• Diphenoxylate is an opioid that slows down movement in your intestines allowing your body to absorb more water and makes your stool firmer (concern for addiction without added atropine as it is an opiod)
• Atropine is an anticholinergic medicine added in very small amount which causes unpleasant symptoms if someone tries to take too much of the drug to get high (since it is an opioid)
• Dicyclomine (Bentyl)
• Treats painful abdominal cramping and spasms
• Side effects of dry mouth, blurred vision, dizziness, drowsiness, and constipation
• Mechanism of action - Blocks the chemical messenger acetylcholine in the gut slowing down gut movements and relaxing smooth muscle in the stomach and intestines
• Ondansetron HCL (Zofran) 
• Treats nausea and vomiting
• Side effects of constipation (no sleepiness) - for use in daytime
• Mechanism of action - blocks serotonin from binding to 5-HT3 receptors in your gut and brain
• Prochlorperaine (Compazine)
• Treats severe nausea and vomiting
• Side effects of sleepiness - for use at night
• Mechanism of action - blocks dopamine D2 receptors in the brain, particularly in the chemoreceptor trigger zone, which stops signals that trigger nausea and vomiting

 Flashbacks to my nausea decision tree from chemotherapy.

 Is anyone else surprised to hear that anti-diarrheals are opioid agonists?

 Here's a helpful image for my medical professional readers out there! The more you know!

 Ok, now I'm really geeking out! What came first, the knowledge that opioids cause constipation therefore using this as the mechanism of action to prevent diarrhea or the development of an anti-diarrheals? The former!!!!

From Google AI:

Yes, traditional opioids came thousands of years before targeted synthetic opioid agonist anti-diarrheals. 

History of Traditional Opioids

• Ancient use: Humans have used raw opium (derived from the opium poppy, Papaver somniferum) for over 5,000 years, with cultivation dating back to ancient Mesopotamia around 3400 BCE. 
• Early anti-diarrheal use: Historical preparations like paregoric (a camphorated tincture of opium) and laudanum were used for centuries to treat severe diarrhea and pain by slowing down the digestive tract.
• Isolation: Pure opiate compounds like morphine were first isolated from opium in 1803 by German chemist Friedrich Sertürner.

History of Opioid Agonist Anti-Diarrheals

• Targeted synthesis: Modern, specialized synthetic opioid agonist anti-diarrheals that focus primarily on the gut without significant central nervous system effects were developed much later.
• Diphenoxylate: Synthesized in 1956 by Paul Janssen at Janssen Pharmaceutica, and commonly combined with atropine as Lomotil.
• Loperamide: Better known by the brand name Imodium, it was first synthesized in 1969 and introduced for medical use in 1976.

 Due to this very game being baseline for me, I am utilizing the Medications tracking option in the Apple Health App. It even allows me to set a critical alert if I have not marked "taken" within 30 minutes of my expected time to keep me on track for the specifics of the clinical trial.

 

How does Verzenio impact disseminated tumor cells?

My 5.5 hour flight from PHL to SEA has already been a great opportunity to study more about the theory of how Verzenio will help me prevent recurrence of cancer. Even without the addition of hydroxychloroquine at this time. What felt a bit like defeat, now feels like an opportunity, the opportunity I felt this clinical trial would bring me from the beginning.

 Abemaciclib (marketed as Verzenio) stops cancer cell division by blocking specific proteins called cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). 

How It Stops the Cell Cycle

• Targeting Proteins: CDK4 and CDK6 normally team up with other molecules to push cells through their growth cycle so they can multiply.
• Blocking Signals: Verzenio inhibits these enzymes, preventing them from activating the retinoblastoma (Rb) protein.
• Causing Arrest: Without this activation, dormant or active tumor cells—including disseminated tumor cells hiding in the body—get stuck in the G1 phase and cannot copy their DNA to divide.

Leading to Cell Death

• Prolonged Stoppage: Continuous exposure to the drug keeps the cells from growing indefinitely. (I will not have continuous exposure to Verzenio. To start, it will be 6 months. Potential for 12 months if needed. No more.)
• Cell Senescence: Instead of multiplying, the arrested tumor cells enter a permanent state of non-division (senescence) or trigger programmed cell death (apoptosis). (Clarification on the word permanent. They enter a permanent state only while taking the CDK4/6 inhibitor (Verzenio) but can return to a potential of division (quiescent) after stopping the medication.)

• Preventing Recurrence: By keeping disseminated tumor cells from waking up and growing, the treatment helps lower the risk of advanced metastasis or cancer coming back. (Google AI)

I've recently started dabbling in AI for images. I couldn't find a good visual until I prompted this diagram on ChatGPT.

This is a good reminder of how disseminated tumor cells are created.

 Senescent or dormant disseminated tumor cells (DTCs) can still be detected in a bone marrow aspirate, but standard microscopic examination alone often misses them because they do not form large tumor clusters and look like single, resting cells. 

• Detection Details
• Specialized Testing: Standard routine stains (like an H&E stain on a basic smear) frequently fail to show single dormant cells. Laboratories must use sensitive methods like immunocytochemistry (using cytokeratin markers) or multiparameter flow cytometry and iFISH to find rare DTCs.
• Cell Cycle Status: Senescent cells are permanently growth-arrested, meaning they do not actively divide, but they remain structurally intact and present in the tissue microenvironment. 
• Clinical Significance: Finding these hidden cells indicates minimal residual disease (MRD), which carries a higher risk of future recurrence even when imaging scans (like PET or CT) show no evidence of spreading. (Google AI)

 Based off of my last pathology report, it states, "A cytokeratin immunostain was performed on the bone marrow cytospins for clinical trial purposes." I confirmed this is the same as "using cytokeratin markers". This tells me, even in their (best clinical trial Arm A outcome) senescent state, any existing disseminated tumor cells should be visible. More on that later. For now, we'll focus on the first 6 months.

Heading home

 

I’m going to let that photo sum up my last few posts. 

I’m sitting on a plane, on 9/11, and want to take some time for those we lost and for those who didn’t bat an eye at walking into the fire. Where were you that day? I was in chemistry class. 

 

Arm A - Verzenio Alone

 

 Well I do, and I will.

 Disclaimer: The third photo down is a photo of my bone marrow aspirate. If you do not want to see it, either stop reading now or plan to skip ahead to the text only.

Me lying on my stomach with bone marrow being pulled into the tube. That is a 9/10 pain my friends. I found deep breathing and humming worked this time. Humming stimulates your vagus nerve through physical vibrations in the throat and vocal cords, which can help reduce pain by shifting the body into a relaxed state. 

 After a long day at UPenn, it was revealed that I would be in Arm A of the study which is Verzenio (abemaciclib) alone. No hydroxychloroquine. While I prepped myself for this, my emotions got the better part of me. 

 I guess therapy did help. I sure am feeling all the feelings. I can tell this is not what people are used to from me by the reactions I'm getting, and that is OK. 

 
 Apparently it is completely normal to feel disappointment, frustration, anxiety, or even altruism when you're randomized into the arm that has been shown to be "lesser" or less effective than the other. Now it is important to remember that the only research we have to date was on mice, and humans aren't mice, so it is not a 1:1 correlation on expected outcomes. That is why I'm here in the first place. 

From Google AI:

• "Disappointment: You had hoped the experimental drug would cure or improve your condition right away.
• Frustration: It feels unfair to miss out on a new treatment just by the luck of a random draw.
• Anxiety: You might worry that your health will not improve or that you are wasting time.
• Altruism: You may still feel proud that your participation helps researchers find answers for future patients."

 This is reality my friends. Things hurt, even when you plan for them not to. I will turn this frown upside down and get back to my more optimistic mindset, but being the realist's optimistic view of cancer, I had to show it all.

 Can't wait to get home to Alaska.

Day 2 - ABBY Trial Bone Marrow Aspirate and Revealing which Medications I will be taking

 

Starting early for today's visits for research labs, my baseline bone marrow aspirate, and meeting with the trial NP to acquire my medications for the next 28 days. 

 Right when I had switched back to long term thinking, I need to return to more of a day by day outlook. What is healing anyway? An acceptance that you've been through the thing and made it, and now you could go through the thing again, and in theory, you'll make it again? 

 I'm more afraid of leaving my parents without a child than I am to lose my life. But being prepared to lose gives me a special edge on wanting to win. It's the drive that keeps me pushing to pursue the latest and greatest to try to prevent the future risk of recurrence in early breast cancer. For me, and for those after me.

Trying not to be a salty beach

   My mom had a great idea to get away to the beach today. We went to Atlantic City and Margate City, NJ. 

 I learned that Lucy the Elephant is a big deal. She is a 65-foot-tall, six-story, elephant-shaped architectural landmark in Margate City, New Jersey, and the oldest surviving roadside tourist attraction in America.

 It was much less crowded at the beaches in Margate City.

We ended our day at a beachfront dinner at Landshark Bar and Grill, right next to the Ferris wheel.

Thanks, Mom!!

Recovery Day - Everything is Figureoutable

  This is what I felt like yesterday.

 It's amazing what a good nights sleep can do for you. I woke up ready to logisticise. Like jazzercise but much less __________ (fill in the blank):

 I will need to return to Philadelphia every 28 days as 28 days = 1 cycle for this treatment. After looking at dates and factoring in flights and family visits, which is part of the reason I chose to do this study in the first place, I think we can make this happen. 

 I mean, every single one of you, who are here to support me. I appreciate it more than you can know. I didn't plan for this. I didn't plan for any of this. And being a planner, that can make you go crazy. But I have found peace in understanding why everything doesn't have to be planned and that I have the skills and support to make it happen. So thank you for being here with me through it all.