Cupid shot a platinum arrow at my lemons

It’s been quite an eventful two weeks since my last post. Today I sit in the chemo recliner to receive treatment cycle #17 with one of my favorite nurses. Today will include some lessons and thoughts for my medical colleagues and non-medical blog followers and big family updates.

Post content includes:
1. CT Results
2. Jason (and Lindsey) save the day
3. Breaking down the analgesic treatment options
4. Oncology visit and plan moving forward
5. New grandchild arrival, just short of three weeks from Asher’s birthday on February 4th this month
6. Blog Post Dedication

I had a routine follow-up CT scan on Valentine’s Day last Monday immediately after dropping my wife Robin at the train station. She was headed to New York City to catch a direct flight out to Salt Lake City the following day in anticipated arrival of our 7^th grandchild due 11 days ago as of today. This will be Hannah’s and Kris’s first baby. While I type, I was just texted that Hannah and Kris are on their way to the birthing center because Hannah is finally in labor and ready to go! She and Kris chose a natural birth setting in a birthing center with a midwife and NP – kudos to Hannah for her fortitude and unyielding strength in “pushing” forward to experience this painful but incredible miracle.  She assured me and family that there are hospitals within in 2 and 10 minutes drive in case of an emergency. Go Hannah!!!

CT Results

The “Cupid” Tomography (CT) Scan came with good and bad news, hence the title “Cupid shot a platinum arrow at my lemons”. Good news is that lungs and liver are unchanged with no visible cancer or lymph nodes. Bad news is there is now significant ascites (maybe a liter) in my peritoneal cavity, most likely what we call malignant ascites (when tumor growth within the peritoneal cavity releases fluid into surrounding space encompassing the abdominal organs). My bowel habits have changed with some blood in the stool, and I’ve been a bit more tired on certain days (although let’s not forget I did a 10.6 mile bike ride with my son Jason about 3-weeks ago). Also, the CT scan showed some narrowing in the transverse colon which may be nothing, especially since previous scans showed intussusception (when the bowel folds inside another piece of bowel like closing a telescope). That could be, but hopefully is not, a tumor outside the colon that’s not visible but pushing against the colon.  This time I had an opportunity to see the images. I don’t profess to be an expert in imaging or radiology, but considering the previous scan came with lots of poop inside the transverse colon, and this time it was clear, and the fact that I saw obvious fluid just north of the transverse colon (plus the telescoping), it is possible that the narrowing is a result of no poop + outside fluid pressure – or maybe not. But the constellation of all the changes (including some increased fatigue) most likely point towards disease progression. Remember, in my previous life I was an oncology/hematology clinical pharmacist following my fellowship – still, though, I also do not profess to be an expert in diagnostics.  In any case, I texted our immediate family to make them aware of the situation and my take on it prior to my scheduled appointment 4 days hence where the findings were to be discussed with Dr. Onc.

Jason (and Lindsey) save the day

With this new news, as you can imagine, poor Robin was reluctant to leave me home alone. But readers here know how close all our neighbors are to us – they are family. And of course Jeff and Shirah (son-in-law and daughter) are just a 20 minute drive away. Robin’s plan was for an overnight stay with my in-laws, and then head out on Tuesday for SLC to meet up with Kris, Hannah, my niece Genna, and the anticipation of baby Colley.  I begged her not to come home. Next thing I know, following my family text, once again, Jason to the rescue.  He called me up around 6 or 7 PM and said he was coming to stay with me – to him (and my daughter-in-law Lindsey), it was not negotiable. He said he’d be to Albany (from DC) at 11:30.  I got ready for bed and was hanging out watching TV when I received a text from him at around 8:30PM saying, “at the airport, see you soon”.  I’m like, wait….what? I thought you meant 11:30AM tomorrow, not tonight.  I mean Mom just left this morning. And my favorite daughter-in-law Lindsey is home in DC with my first grandson Jonah and sweet little sister Penny. Whatever this disease brings, I just love my family, literally to death!

 

 

 

 

 

 

 

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Jason got to meet Asher and hang with Asher’s sister Aria and of course his sister Shirah and brother-in-law “Little” Jeff.  During Jason’s visit, so far we hung a new shade, we walked Meeko a couple of times in this damn frozen tundra, went shopping at the local mall, he did various chores, the most entertaining of which was cleaning up frozen dog poops that up until a few days ago were buried in ice and snow. We were hosted by Shirah and Jeff for dinner, our lifelong friends Ron and Joanne had us to dinner twice (watching Ron and Jason “debate” was AWESOMELY entertaining), and Shirah’s mother-in-law, Joyce brought us homemade ziti with fresh Italian bread. I’m a lucky guy and so is my family regardless of my fate.

Breaking down the analgesic treatment options

My last several treatments included 5-fluoruricil (leucovorin as an enhancer), and bevacizumab (aka Avastin, a monoclonal antibody). About 5.5 months earlier I was receiving my original regimen of FOLFOX (that’s an acronym for 5-fluoruricil (leucovorin as an enhancer), and oxaliplatin.  If you’ve been following my blogs, you’ll recall that I came off oxaliplatin due to increasing neuropathy, potential for delayed and more severe neuropathy, and the fact that studies supported no greater benefit from 6 versus 12 treatments.¹ But it was working! The blood in my stool is most likely a result of combined issues.

1. Internal hemorrhoid due to forced straining (as I anticipate writing a prior authorization appeal letter to BCBS – that will be quite educational for all of you when I share it).
2. Meloxicam, although relatively COX-2 specific can still cause GI bleeding from peptic and/or duodenal ulcers, and certainly could enhance bleeding from a hemorrhoid, although admittedly far lower risk than let’s say naproxen or ibuprofen.² Note that the study referenced here shows a very low bleed risk with doses of 7.5mg per day. I was using 15mg to offset some of the COX-2 specificity because of clot risk with elevated platelets and other cardiac risks with my chemo regimen.
3. Bevacizumab, which I outlined in previous posts works by binding to and inhibiting vascular epithelial growth factor which decreases angiogenesis (development of new blood vessels), tumor growth and disease progression.

So, what should we pharmacists recommend here?  Correct – stop meloxicam and replace with an analgesic that does not increase bleeding risk.  For me, the choice was acetaminophen. It works, I suspect because I don’t think we’re talking about an overwhelming tumor load compared to when I first started treatment last spring which clearly required a steroid, an NSAID, or a pretty good dose of an opioid. Second, nix the bevacizumab, at least for now. I can be treated again with this alone or combined with ??? (see below).

Oncology visit and plan moving forward

I must say, I have come to really like Dr.Onc – let’s just say we’ve both learned to have a mutual respect for one another, and I feel like a team member rather than a chess piece moving along an assembly line. In fact, this week the compassion in her/his eyes was obvious when s(he) confirmed exactly what Jason and I played in our minds many times this week. S(he) suggested we stop bevacizumab and start irinotecan in lieu of it. For some background information, irinotecan is in fact the second line treatment for colorectal cancer following FOLFOX.  The acronym here is FOLFIRI, 5-fluoruricil (leucovorin as an enhancer), and irinotecan (a topoisomerase inhibitor that blocks cell mitosis). The problem of course is that it is VERY toxic, as all of our cells replicate by mitosis. The intent here is similar to the original regimen, where irinotecan replaces oxaliplatin.

I don’t pretend to know all the answers – irinotecan and oxaliplatin weren’t even available when I practiced oncology. So, I asked Dr. Onc to give me an honest answer and not to be influenced by my question, “Could/would a rechallenge with oxaliplatin be just as effective as irinotecan 180mg/M2 every two weeks?”.  Dr. Onc first smiled and said, “that’s impressive that you knew what I would choose and the dose”. In the back of my mind, I’m thinking that irinotecan is the last option for me as a single agent, but other options do include using it in addition to bevacizumab and/or combined with oxaliplatin. Dr. Onc said YES (with some tears in her/his eyes), although we both recognized the neurotoxicity and infusion reaction risks are elevated with a rechallenge.^3,4 Our relationship has pleasantly blossomed over the last several months, and it was clear without words that Dr. Onc respectfully acknowledged (without words) my complete understanding of all the implications discussed at this visit.

All that aside, I’m thinking that with regard to oxaliplatin and irinotecan, the devil I know is better than dying from irinotecan or at the very least, saving it for a last hurrah, alone or combined with treatments mentioned above. Of course, my astute resident graduates will know I’m going to want some pharmacogenetic testing specific to irinotecan with the presumption that eventually I will be receiving this medication. Glucuronosyltransferase (UGT)1A1*28 gene is important in predicting irinotecan risk for severe neutropenia. And if you didn’t know, please read up on it in case my mind starts to slip and I need help remembering or understanding it all.  LOL, that’s not happening! I have a note into my Sloan Kettering doctor, but I won’t be able to get his opinion until after the oxaliplatin today. I also intend to discuss with him Phase II colorectal vaccine trials.

New grandchild, again?!?!
It is now 12PM and Hannah is 5 cm dilated. If there’s a baby arrival soon after this post, here’s where I’ll place a picture and give more details.
UPDATE: It’s a boy! No name yet. I’ve been respectfully sworn to no social media pics. But I can say that all is great. Hannah and Kris are doing well. Baby Colley is healthy, was born 2/22/22, 7.4 oz. 21 inches long and “doesn’t stop moving unless he’s eating according to mom and dad.”

In closing, Cupid’s platinum arrow is that of Oxaliplatin, a platinum-based cytotoxic medication, hitting me in the lemons (sort of speak). There were lots of pharmacotherapy lessons in today’s post. I have a flight headed out to SLC right after my portable pump disconnect on Wednesday to meet my new grandchild and visit with the crew – I may have cancer, but I’m still kicking. And, I will likely be able to kick harder, because after a few treatments with oxaliplatin, it won’t hurt my foot as much!

Blog Post Dedication: This post is dedicated to our dear neighbor Anne Phillips who succumbed to uterine cancer 6-weeks following diagnosis and passed on February 1^st three weeks ago. This reminds us just how fragile life is and that time enjoyed with family and friends should be cherished, ALWAYS. We all loved her dearly.  Our hearts, thoughts, and prayers are with her husband Tom, daughter Amy, and their entire family!

Comments are enthusiastically welcomed. I love receiving comments on various social media platforms (Facebook, Linkedin, Twitter), but please also paste those comments on here if you have time! 

References

1. Chibaudel B, Maindrault-Goebel F, Lledo G, Mineur L, André T, Bennamoun M, Mabro M, Artru P, Carola E, Flesch M, Dupuis O. Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. Journal of Clinical Oncology. 2009 Dec 1;27(34):5727.
2. Barner A. Review of clinical trials and benefit/risk ratio of meloxicam. Scandinavian Journal of Rheumatology. 1996 Jan 1;25(sup102):29-37.
3. Mori Y, Nishimura T, Kitano T, Yoshimura KI, Matsumoto S, Kanai M, Hazama M, Ishiguro H, Nagayama S, Yanagihara K, Teramukai S. Oxaliplatin-free interval as a risk factor for hypersensitivity reaction among colorectal cancer patients treated with FOLFOX. Oncology. 2010;79(1-2):136-43.
4. Yanai T, Iwasa S, Hashimoto H, Kato K, Hamaguchi T, Yamada Y, Shimada Y, Yamamoto H. Successful rechallenge for oxaliplatin hypersensitivity reactions in patients with metastatic colorectal cancer. Anticancer research. 2012 Dec 1;32(12):5521-6.