Thankfully, yesterday’s cardiology appointment and weekly chemotherapy session were both uneventful. The mystery fever hasn’t come back and I haven’t had any more rapid heart episodes since my last visit to Memorial Sloan-Kettering Cancer Center’s (MSKCCs) urgent care facility.
Before my first appointment, we had a chance to stop by and say “hello” to Dr. Susan Slovin at MSKCC for a few minutes. She specializes in prostate cancer, clinical immunology, and other genitourinary malignancies. If you’ve read my memoir, you are aware that we’ve known each other for quite some time and that she is a trusted resource and friend. As always, she had some words of wisdom to share and put a smile on our faces. Truly a great start to the day – thank you Dr. Slovin!
The cardiologist did change my medication, as the beta blocker I was taking (metoprolol) also resulted in some fairly low blood pressure readings and lightheadedness when going from a sitting to standing position. But again, minor complaints compared to being in the intensive care unit (ICU) a short while ago. My latest EKG looked fine and I simply need to follow-up in one month.
The consensus seems to be that my rapid heartbeat was caused by a perfect storm consisting of a high fever, low electrolytes, and possible bacterial infection. So, my job is to help make sure not to repeat these circumstances by keeping hydrated and getting plenty of electrolytes.
In terms of chemotherapy, my blood counts are doing well – especially after last week’s doublet of carboplatin and paclitaxel. While I only get carboplatin every three weeks, it does seem to hit me much harder than the paclitaxel alone – especially with regard to appetite. In any event, yesterday’s chemo session went as planned with just the paclitaxel and various premedication.
We finished everything by early evening and planned on staying in NYC overnight rather than rushing to get home. Since I was hungry for a change, Lorie and I went to the hotel’s rooftop bar and enjoyed dinner outside under the stars. It’s moments like those that make everything worth it – and I savor every one.
The rescheduled visit by my sister and her family went well this past weekend. I haven’t made it back to Chicago to see them in a while and I was amazed by how much their two boys had grown since I last saw them. It meant a lot to be able to spend some quality time with all of them and I appreciate their long drive back-and-forth from Illinois to Pennsylvania just to see me (okay, perhaps they really came to see Humphrey…).
The plan for now is continued weekly chemotherapy with a possible break during Labor Day week. Treatment would then resume with an eye towards imaging in early October to see how things are progressing – or perhaps more optimistically “regressing.”
Knock on wood, things will remain calm for a bit as Lorie goes back to work and our girls return to school. It’s always a stressful time for them, so it would be nice for my disease to behave for at least a little while.
Lastly, I recently gave my book website a makeover, so please take a look and let me know what you think at www.awalkwithpurpose.com
Bacterial cultures from the tips of two chest tubes that were recently removed revealed growth of a pseudomonas organism on one of them. These are fairly common pathogens involved in infections acquired in a hospital setting. Whether or not this was the source of my fevers, I was prescribed an antibiotic (levofloxacin, 500mg daily) since pseudomonas can lead to other nasty conditions.
I continued running fevers for a few days after starting the antibiotic, but was free of fever for the 48-hours leading up to my next scheduled chemotherapy round. Aside from the mystery fever, my blood counts have been good throughout the three weeks of chemotherapy that I received thus far. Accordingly, my medical oncologist (Dr. Pfister) supported resuming treatment.
On Tuesday, August 15, 2017, Lorie and I took the early morning train to NY so I could receive an intravenous infusion of paclitaxel and then carboplatin as planned. I was quite anxious to resume treatment after a one week break – especially after seeing the decrease in tumor size from the recent CT scan.
I looked at my blood test results from that morning and noticed my magnesium level was again low. Knowing that this “could” have played a role in the recent cardiac event, and that my daily oral magnesium isn’t keeping up, I requested an additional intravenous course of magnesium just to be safe and the medical staff agreed.
The chemotherapy infusions went well and we were able to take an afternoon Amtrak train back home. Benedryl® is one of the pre-medications they give me, so I slept a good portion of the trip home. Lorie was kind enough to capture me asleep with her phone.
After postponing their prior trip due to my hospitalization, my sister and her family are planning to visit us this weekend. Hopefully life is uneventful and we all get to spend some time together.
It was surreal that exactly one week after being in the intensive care unit (ICU) at Memorial Sloan-Kettering Cancer Center (MSKCC), I felt good enough to participate in a scheduled radio interview conducted in Philadelphia on August 10, 2017. Just goes to show there are good days and there are bad days. NPR member radio station WHYY host Dave Heller knew an awful lot about my book “A Walk with Purpose: Memoir of a Bioentrepreneur” and it was so great working with him during my first experience in a radio recording studio. Please take a moment to listen to a replay of this 20-minute segment and other events, along with reading newspaper and other media reprints, under the “In the News” menu tab at my memoir website by clicking here.
Hopefully I continue to feel okay the next couple of days and look forward to seeing family while in town. It should take a week or so for the latest treatment effects to materialize. If not, however, I’m sure Humphrey will provide them with endless hours of amusement!
I would be remiss if I didn’t mention in closing that the start of the new school season is a great time to schedule an appointment with your pediatrician to talk about an important immunization that could prevent 6 cancers in boys/girls. You can learn more about this vaccine in an earlier blog post by clicking here. Had this vaccine been available when I was a child, it could have prevented the cancer that’s killing me. Start the discussion with your doctor – today! And help spread the word by using the #DiscussHPV hashtag in your social media posts.
My recent hospitalization was the longest and most volatile, resembling that of a roller coaster ride at an amusement park. What started with a fever prompting our arrival at Memorial Sloan-Kettering Cancer Center’s (MSKCC’s) urgent care facility in New York last Thursday evening ended up escalating to a brief visit to the intensive care unit (ICU) as detailed in my prior post.
The isolated cardiac event appears managed by medication (metoprolol) and hasn’t reappeared. However, despite numerous blood cultures, chest x-rays, CT scans, and other diagnostics, the cause of my fever – the original reason for my hospital visit – remains a mystery.
After an infectious disease consult, bacterial infection was ruled out as the likely source of the fever and I was taken off the broad-spectrum antibiotics that were being delivered via intravenous infusion. Some of the cultures take time to process, so there is always a chance that something will materialize in the coming days.
One silver lining amidst the tight turns, steep slopes, and inversions on my roller coaster ride was the fact that my left lung appeared much improved in terms of fluid accumulation. This coincided with almost zero drainage from my two chest tubes over the past week or so and it was determined that removing both of them was in my best interest since they weren’t serving any functional purpose and there is always a risk of infection in having two foreign objects in the body.
Insertion of the two chest tubes (one while at the National Institutes of Health and the other at MSKCC) was done under twilight anesthesia, where I was awake but sedated. This is accomplished via administration of a concoction of agents including a benzodiazepine (midazolam) and the narcotic fentanyl. For both procedures, I had little if any discomfort.
Naturally, I expected that removal of the chest tubes would also be done under twilight anesthesia. Much to my chagrin, I was informed that the extraction procedure is normally done bedside and without anesthesia. Two medical professionals arrived at my room at MSKCC and provided a reasonable explanation for the lack of lidocaine or other local anesthesia (the injections would hurt more than the extraction, several would be needed to cover the entire area, and risk that the tubes could be punctured via the needles).
Ever since their initial placement, I’ve been anxious when cleaning or touching the plastic tubes that protruded from the front of my left chest. There was just something unnerving about seeing the foreign tubes that looked like they would be better suited on a Borg, a fictional alien group that appeared in the Star Trek franchise.
As such, you can imagine my surprise as one of the medical professionals from interventional radiology wrapped the first tube around her hand and proceeded to yank it with the same intensity as trying to start a lawn mower by pulling the cord. To be fair, the pain wasn’t terrible and this was one of those situations where speed was definitely better than dragging it out. Nonetheless, I was shocked by the experience and now had an idea what extraction of the second tube would be like.
The first tube was easy by comparison, as it was only placed a short while ago. The second extraction was more difficult as that tube was in place for 4-months and had grown quite attached to me. The first attempt yielded little, if any, movement from the tube. Fortunately, the second try was successful and I am now “tube free.” The tips of both tubes were cut and sent to be cultured in case either was the source of infection that was causing my fevers.
There are plenty of other possibilities to explain my fevers, including the tumors, blood clots, and others. For now, the plan is to carefully monitor my temperature and hope that it continues to respond to Tylenol®. If not, we’ll be back at the hospital.
In view of the current situation, my medical oncologist (Dr. Pfister) appropriately held back on this week’s cycle of chemotherapy to be safe. Encouragingly, the CT scan used to look for pneumonia and other potential reasons for the fever provided a sneak peek of how the tumors responded to the first three weeks of chemotherapy and almost all of them showed decreases in size. This is definitely better than having the tumors grow or stay the same size, but likely doesn’t change the “terminal” nature of my disease. It does, however, hopefully buy me some more time.
It’s great to be back home and I cannot wait to see my daughters and the petting zoo…especially Humphrey! And words cannot begin to express our family’s gratitude for all of the many people that helped out while we were at MSKCC the past 5-days.
On Tuesday, August 1, 2017, I received my third dose of chemotherapy. Everything went well and the next day I was feeling excellent, although some of that can be contributed to the steroid pre-medication. As an added plus, I was looking forward to having family in town for the weekend. Life seemed pretty good.
In the back of my mind, I knew that I likely hadn’t reached the nadir, or lowest point, in my blood counts from the prior chemotherapy. As such, there was a possibility that I might not be feeling 100% for my visitors.
Sure enough, by Wednesday evening I started running a mild temperature. No big deal – it was below the 38 degrees Celsius (°C) cutoff for an “official” temperature. On Thursday I wasn’t feeling energetic and napped most of the day. Then the real fun started.
My temperature rose Thursday evening and the physician-on-call at Memorial Sloan-Kettering Cancer Center (MSKCC) recommended that I come to urgent care to get things checked out. So, Lorie and I made the drive from Bucks County, PA to New York City for the third visit to urgent care within the past three weeks! We debated taking the train as opposed to driving, which would have been faster.
By the time we arrived at MSKCC, my temperature was above 39 °C and I felt the familiar muscle aches and general fatigue that I associated with influenza. Coincidentally, it was the diagnosis of influenza during my first week of chemoradiation in early 2016 that resulted in my first trip to MSKCC’s urgent care facility.
Flu season doesn’t usually begin until October, so this time concern focused on bacterial infection. With my white blood cell counts negatively impacted by chemotherapy, it was possible that my body couldn’t fight off an infection in one of my chest tubes or another location.
I was triaged with the usual battery of blood tests and a chest x-ray before being placed in an exam room. Urgent care was very crowded and I was just happy to have a bed and looked forward to resting horizontally for a while.
I sat on the bed, preparing to relax when I clutched my chest from a sudden, stabbing pain. Lorie could tell from the expression on my face this was no ordinary situation and called for the nurse who arrived immediately to assess the situation. As various cables were connected, I felt my heart racing and Lorie was shocked to see my pulse was 225 on the computer monitor.
Normally, the heart beats about 60 to 100 times per a minute at rest. But in tachycardia, the heart beats faster than normal in the upper or lower chambers of the heart or both while at rest. The episode ended within a minute or so, but tachycardia can disrupt normal heart function and lead to serious complications, including heart failure, stroke, and sudden cardiac arrest or death. Patches were promptly applied outside of my chest wall, which could be used if needed to provide a brief electric shock to the heart to reset the heart rhythm back to its normal, regular pattern.
My heart wasn’t the only one racing as the medical team placed a crash cart outside my door and a sense of urgency filled the room. The contents of a crash cart vary, but typically contain the tools and drugs needed to treat a person in or near cardiac arrest. I was sure that the end was near.
Fortunately, no further cardiac events occurred and I was admitted to MSKCC’s intensive care unit (ICU), where seriously ill patients are cared for by specially trained staff. While I have never had the misfortune to be admitted to an ICU in the past, I was amazed by the both the medical staff and technology used to monitor my condition and knew I was in good hands.
I was placed on an antibiotic and medication to stabilize my heart rate while the team worked to determine the source of the tachycardia and whether or not my episode had caused any damage to my heart. Preliminary assessments ranged from one of my tumors or chest tubes rubbing up against the sensitive tissue surrounding the heart to low electrolyte levels, which are important minerals in your body that have an electric charge. Maintaining the right balance of electrolytes is key for your body’s blood chemistry, muscle action and other processes.
On Friday, my temperature returned to normal and there were no further cardiac events. Still, I couldn’t help but feel that perhaps it was time to contact hospice and let the cancer take its course. I had faced my share of obstacles since being diagnosed with cancer in late 2015 and three recent trips to the hospital resulted in further erosion of my quality of life with two chest tubes, being back on chemotherapy and its side effects, and now the prospect of potential cardiac issues. Lorie and I discussed the topic of hospice and she rightfully pointed out that such a decision shouldn’t be made while sitting in the ICU.
I shared my thoughts about hospice with one of nurses while he assisted me with walking a few laps around the floor. Much to my surprise, he shared with me that it was about 11-years ago that he underwent a bone marrow transplant at MSKCC and how it caused him to pursue a career in medicine. He discounted my outlook on hospice, stating that I was young, up-and-walking, and seemed otherwise quite capable of enjoying further quality time with my wife and daughters. When my quality of life truly diminishes, that would be the time to consider hospice.
Our daughters, Rosie and Megan, traveled by train to NYC and were able to visit me briefly in the ICU. However, they all stayed overnight in a nearby hotel thanks to my father and step-mother. Being in the ICU wasn’t conducive for the planned family visit, which unfortunately got cancelled.
I was released from the ICU to a regular room very late Friday evening. I’ll be here for at least another day or two because the source of the fever still hasn’t been identified. With the fever gone, it appears the antibiotics were successful in treating the infection, but without knowing the source or strain – treatment can be challenging.
Viewing my Twitter feed briefly from the ICU on Friday, I was delighted to learn that Adam Feuerstein, Senior Writer at STAT News (statnews.com), Tweeted that he was dedicating his Pan-Mass Challenge ride to me.
Each year the Pan-Mass Challenge brings together thousands of impassioned cyclists, committed volunteers, generous donors and dedicated corporate sponsors. Together, they strive to provide Dana-Farber’s doctors and researchers the necessary resources to discover cures for all types of cancer.
“Michael, we love you, support you. Your strength will inspire me tomorrow.,” Tweeted Adam. Well, Adam, your Tweet and the many acknowledgements on Twitter helped brighten my day and I’m still here giving cancer everything that I’ve got. Godspeed on your ride and thank you for an amazing gesture!
And special thanks to all of Lorie’s friends who have helped our daughters get to NYC and/or babysit our small petting zoo while we’re away. It’s a lot to ask, and we’re so grateful for the help since it is one less thing to worry about. Humphrey appears to have made new puppy friends, as evidenced by the photos and videos that I love seeing.
It’s Saturday afternoon as I finish writing this blog update. Lorie, Rosie, and Megan are able to visit longer since I’m in a regular room now. Seeing people in the hospital isn’t tops on most teen’s lists of favorite activities, but it means so much to me having them here.
Life has been hectic since this past Sunday when Lorie and I drove to New York City for another visit to Memorial Sloan-Kettering Cancer Center’s (MSKCCs) urgent care facility. Drainage from my chest tube once again changed from amber fluid to the color of a fine Cabernet wine, which signaled that bleeding resumed. More alarming was the accompanying shortness of breath and increased coughing. I was out of breath even from walking a short distance to go to the bathroom.
We arrived at MSKCC around 10am and, following a brief review of recent events, had a chest x-ray taken to get a quick read on the situation. The resulting images showed a complete “white-out” in the left lung, which indicated that fluid had essentially filled the entire space. Normally, the lungs look transparent or black on an x-ray due to air in the lungs.
The fact that I had only one viable lung explained the shortness of breath and coughing. What the x-ray couldn’t reveal was the composition of the fluid (serous fluid, blood, tumor) or its source. For more information, a CT scan was required and scheduled. Unfortunately, weekends at any hospital can be hectic and my CT scan didn’t take place until close to midnight and I was admitted.
Monday morning, we had the pleasure of meeting again with surgeon Dr. Bernard Park, deputy chief of clinical affairs, thoracic service at MSKCC. In December 2016, Dr. Park had successfully performed a bronchoscopy procedure to biopsy a suspicious lymph node near my airway. We knew that we were in good hands.
Dr. Park explained the situation and the requisite next-steps were abundantly clear. For whatever reason, the Aspira Pleural Drainage Catheter in my left lung wasn’t fully draining the fluid – especially towards the top section of my lung. That fluid needed to be drained in order to alleviate shortness of breath and coughing. How to best accomplish this was a source of significant discussion.
One short-term solution was to temporarily insert a plastic tube straight through the front of my chest into the top section of the lung to manually extract the fluid. This would require a brief stay in the hospital while the tube was present and it would be removed prior to going home. A longer-term solution was to place a second PleurX catheter that could be accessed whenever needed at home to extract fluid from the top section of the lung.
In either case, a potential pitfall was that the fluid in the upper section of the lung may actually be fibrotic scar tissue (called loculation) or tumor, preventing effective drainage. Dr. George Getrajdman, an interventional radiologist at MSKCC, proposed a step-wise procedure. First, he would try to extract the fluid near the top of the left lung using a syringe to see “if” anything could be extracted. If so, he could confidently proceed with placement of a second catheter (Option A) or the fluid could simply be drained with the syringe to see if that provided symptomatic relief before proceeding with more permanent catheter placement (Option B). Placing a temporary plastic tube was also a consideration (Option C), with the downside being that fluid accumulates again in the future – requiring another procedure. If no fluid could be extracted with a syringe, then the space was being occupied by something more solid (fibrotic scar tissue and/or tumor mass) and a catheter would be pointless. Ultimately, I decided to proceed with Option A.
Requiring more urgent resolution, however, was the recently discovered blood clot in my iliac vein near the pelvis and its potential to detach and cause a pulmonary embolism (PE) – a condition in which one or more arteries in the lungs become blocked by a blood clot, which could stop blood flow to the lung. With essentially only one lung functioning, a PE in my remaining viable lung would likely be fatal. Hence the sense of urgency.
Due to the recurrence of blood in the drainage from my original chest tube, we reached the point where taking anticoagulant medication (Lovenox®/ enoxaparin sodium) to treat and prevent deep vein thrombosis (DVT) was no longer viable and was discontinued. The only alternative was placement of an inferior vena cava (IVC) filter device designed to trap/prevent my blot clot from traveling from the largest vein in the body, the inferior vena cava, to the lungs or heart.
To insert an IVC filter, I was given medication to help relax and a local anesthetic to numb the area of insertion. Implanting the IVC filter was Dr. Getrajdman, who inserted a catheter through a small incision in my neck. Using X-rays images to guide the procedure, he advanced the IVC filter through the catheter and into the inferior vena cava. Once the IVC filter was in place, he removed the catheter and put a small bandage on the insertion site.
Fortunately, Dr. Getrajdman was also able to deal with the left lung issue during the same procedure. Approximately 1.5 liters of fluid were successfully acquired from the top portion of the lung, so he proceeded with placement of a second catheter as planned/hoped. Both procedures took about 1.5 hours in total to complete. Afterwards, an x-ray confirmed that the top portion of the lung was free of fluid as shown in the accompanying image.
My breathing improved immediately following the procedure and I felt fine with all of the pain medication. However, waking up the next day (Tuesday) I felt like I’d been hit by a truck. There was a fair amount of pain at both the incision on my neck from the IVC filter insertion and the newly placed catheter site. As the day progressed, the pain diminished and I started feeling much better.
By late afternoon, tissue plasminogen activator (TPA) was injected through my original Aspira chest tube to help clear the line by breaking down blood clots. Afterwards, we were trained on using the “new” PleurX catheter and then proceeded with draining fluid from both the top and bottom catheters. The top PleurX catheter rapidly drained 500cc of fluid, which looked far less bloody than what had previously been extracted from the bottom. We were only able to drain 200cc of fluid from the bottom Aspira catheter, which was still bloody and thicker. It’s speculated that the fluid from the bottom was left over from before and there was no active bleeding, which will be confirmed by monitoring hemoglobin levels.
With the IVC filter in place and the ability to drain both top/bottom fluid from my left lung, I was able to proceed with my second dose of chemotherapy while in the hospital. This consisted solely of paclitaxel and then next week should be my initial loading dose with cetuximab.
We’re planning to try draining both chest tube sites today (Wednesday) and looking for further improvement in subsequent chest x-rays. Assuming all goes well, I should be released from the hospital but need to stay in NYC overnight and see my oncologist tomorrow. I’m feeling much better now, but the coming days should be when the effects of my first week of chemotherapy (paclitaxel/carboplatin) start materializing. In any event, I’ll be happy to get home hopefully tomorrow and see how big our new puppy Humphrey has grown in the short time we’ve been away.
Despite the hectic backdrop of late, I’ve been busy researching treatment options for patients like me with incurable squamous cell carcinoma of the head and neck (SCCHN). My first inclination was to pursue another immunotherapy, as there are a lot of clinical trials with novel immunotherapies and combinations currently recruiting. With my disease progressing, however, I felt that perhaps a more aggressive approach backed by data was warranted.
For example, one viable option is the chemotherapy-based “EXTREME” regimen with 5-fluorouracil (5-FU), cisplatin or carboplatin, and the monoclonal antibody Erbitux® (cetuximab). Initially, I discounted this option because 5-FU-based regimens can be associated with significant toxicities. Nonetheless, a multicenter phase III trial in SCCHN demonstrated a 36% longer median overall survival using the EXTREME regimen versus chemotherapy alone (10.1 months vs. 7.4 months, respectively). It was the kind of data-based treatment I was seeking, but I was really against receiving 5-FU.
One of the many nasty side effects from 5-FU is palmar-plantar erythrodysesthesia (PPE), also known as hand-foot syndrome (HFS). There are currently no treatments or preventions for HFS, which is characterized by tingling in the palms, fingers and soles of feet and by erythema, which may progress to burning pain with dryness, cracking, desquamation, ulceration and oedema.
I learned a lot about HFS while serving as CEO of VioQuest Pharmaceuticals. The company was developing a 1% uracil topical formulation to prevent HFS. Uracil is a naturally occurring substrate that directly competes with 5-FU for the enzymes that metabolize 5-FU to its toxic metabolites. When applied topically, the concentration of uracil in the skin greatly exceeds the concentrations of 5-FU, thus blocking the formation of 5-FU’s toxic metabolites. Unfortunately, there haven’t been any updates on the product’s development status since April 2010 according to ClinicalTrials.gov.
When we arrived at Memorial Sloan-Kettering Cancer Center (MSKCC) late Sunday evening, I had already decided that if it came down to the EXTREME regimen as my best option – I would simply forgo further treatment, contact hospice, and let things progress naturally.
Fortunately, my medical oncologist at MSKCC, Dr. David Pfister, suggested replacing 5-FU with weekly paclitaxel, resulting in a chemotherapy regimen known as PCC (paclitaxel, carboplatin, and cetuximab), that has been found to be efficacious and well-tolerated in patients with SCCHN when used as induction chemotherapy. As a result, 5-FU and paclitaxel can be viewed as somewhat interchangeable, but paclitaxel offers a more favorable toxicity profile.
Unlike the two chemotherapeutics, cetuximab is a chimeric human-murine monoclonal antibody (mAb). MAb therapy, the most widely used form of cancer immunotherapy today, is a form of “passive” immunotherapy that often does not require the patient’s immune system to take an active role in fighting the cancer.
Cetuximab targets and binds to epidermal growth factor receptors (EGFR) that are found on the surface of many normal cells and cancer cells. Doing so stops the cell from continuing the signaling pathway that promotes cell division and growth, effectively stopping the cancer by stopping the cancerous cells from growing and multiplying.
I’m a big believer in the power of immunotherapy and believe that my recent treatment with the experimental M7824 (first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap) had a positive effect on my disease. More importantly, there may even be synergy between what M7824 has done so far in combination with the PCC regimen. Even if the PCC regimen only shrinks my lung tumors, the reduction in disease burden could help future immunotherapy treatments be more efficacious.
Having plenty of time to weigh the future treatment options while the bleeding issue with my chest tube was being addressed, I decided that Dr. Pfister’s proposed PCC regimen made a lot of sense. Much to my surprise, I was able to start treatment with the two chemotherapeutics (paclitaxel and carboplatin) on Tuesday and return home that evening. Next Tuesday I will receive my first loading dose of cetuximab.
Regarding the bloody drainage from my chest tube referenced in my prior post, I had a liter of fluid drained using a vacuum-like device connected to my catheter and the drainage returned to a healthier apple juice color. I was started on Lovenox again while continually monitoring the fluid output through the tube looking for the color to change back to bloody. Fortunately, the color remained the same and it looks like Lovenox wasn’t the likely culprit. I’m back on Lovenox and so far, so good.
I never thought I’d say the phrase “I’m back on chemotherapy.” But here I am, continuing the fight. Why? Because Lorie slept at a hotel on our second night in NYC to get some much-needed rest and my mind went drifting down memory lane as I sat alone in the patient room at MSKCC. I thought about all the good times we shared, the family we raised, and how much we love each other. I cried and cried. Suddenly, I knew that if chemotherapy could give me even just one more day with her, it would be worth the drug’s side effects.
And yes, there is still the hope of doing better and living longer than expected. The chances are remote, but not zero. More updates soon…
As discussed in my prior blog post, the recent CT scan at the National Institutes of Health (NIH) didn’t turn out as we had hoped. Not only did the cancer show signs of progressing, but a blot clot was also found in my left iliac artery near my pelvis.
I had been on Lovenox (enoxaparin) for just under one week, when I noticed that the daily drainage from my chest tube looked much more like blood than the usual straw color. Equally disconcerting, the volume of drainage was greater than usual.
At the suggestion of my treating physicians, we stopped at the emergency room at a local hospital in Bucks County (which will remain nameless) on Sunday morning around 10am simply to have a complete set of blood work done. The concern being that the loss of so much blood via the chest tube could necessitate a transfusion.
Fortunately, my hemoglobin levels were okay (low hemoglobin count may indicate you have anemia) and a transfusion wasn’t needed. However, a big problem remained – finding the cause of bleeding coming from my pleural effusion and how to stop it.
One thing was almost certain – the anticoagulant Lovenox likely played a role. Discontinuing Lovenox could help reverse the bleeding, but I would be left with an untreated blood clot that could cause major problems if it moved from its current location. Damned if i do, damned if i don’t.
Quite the conundrum and not one to take lightly. As such, after waiting around the local hospital until early evening with no solutions, nurses, or physicians in sight, Lorie took control and requested that I be immediately discharged. Shortly thereafter she drove us to New York City to visit Memorial Sloan-Kettering Cancer Center (MSKCC). I already had an appointment scheduled with my medical oncologist (Dr. David Pfister) for Tuesday to discuss possible next-steps for treatment, such as chemotherapy, and the drive to NYC is shorter than going to the NIH in Bethesda, MD.
We arrived after midnight, but the urgent care team at MSKCC promptly assessed my condition. More blood work was drawn along with a chest x-ray and CT scan. Simply looking at the chest x-ray, I could tell that the pleural effusion was quite large. This shouldn’t be the case, as I drain it daily.
For now, stopping the internal bleeding is more important than addressing the blood clot – although both issues require immediate attention. I’ve already discontinued the Lovenox and the MSKCC team will assess various options to access and drain the large amount of fluid still trapped in my left lung. The impact of the fluid is not insignificant, as I am short of breath walking short distances or up/down stairs. Coughing also has gotten worse and leads to feeling light-headed or dizzy.
Assuming the pleural effusion can be controlled, the next step would be to deal with the blood clot. One solution is to place a filtering device in the Inferior Vena Cava (IVC, a large vein in the abdomen that returns blood from the lower body to the heart) that could help prevent a pulmonary embolism, which is fatal in one-third of patients who suffer from it. The filter essentially traps blood clots and prevents them from reaching the lungs or heart.
Of course, aside from the aforementioned, I am interested in exploring potential new treatment options and look forward to upcoming physician appointments. Until then, I’ve been admitted to MSKCC for at least a day or two and will provide any meaningful updates via Twitter, etc.
After a full day of activities yesterday, Lorie and I decided to grab an early dinner in Bethesda, MD at a restaurant recommended to us. We really haven’t explored much of the local establishments, so it was nice to venture out and try something new.
We sat down and I immediately focused on the cheese appetizer selection and ordered three different types. Half way through the appetizer, however, my cell phone rang. It was Dr. Strauss from the NIH.
I could tell from the initial line of questioning (are you still at NIH, where are you now, are you alone, etc.) that bad news would shortly follow. Sure enough, yesterday’s CT scan revealed a deep vein thrombosis (DVT) on the left side of my pelvis and Dr. Strauss requested that we promptly return to NIH to start treatment with Lovenox (enoxaparin). With that, we paid our restaurant bill and left our dinners behind to take an Uber back to NIH.
VIDEO CAPTION: 3D CT image from NIH showing tumor locations highlighted in green. The largest mass (lower right) is from my spleen.
Both Dr. Gulley and Dr. Strauss met us back at NIH in the day hospital and we went to an empty treatment room to talk in private. Unfortunately, the blood clot was merely a sideshow for the bigger news, which was that several tumors increased in size from the prior scan taken 6-weeks ago. For the first time, my outlook was black & white: the cancer was winning the tug-of-war with my body’s immune system. Receiving further treatment with the experimental agent M7824 would be hard to justify and more aggressive treatment, such as chemotherapy, appeared to be the favored next step.
After a brief tutorial on self-injecting Lovenox twice daily, we returned to the hotel and planned on meeting early the next morning to review the CT scans and have further discussion. The mood was somber and neither one of us slept very well.
The NIH is only one of two places to have advanced imaging technology that was truly fascinating and dramatically improves the ability to visualize and follow specific tumors over time. Personally, I was amazed by the progress radiology has made since I last reviewed such images. We were engrossed in discussion about the various images displayed on the three monitor screens when Lorie’s phone rang. It was our oldest daughter Rosie.
The first few calls were easy to dismiss since we were in an important meeting, but then came a text – “emergency.” Driving home from class, Rosie apparently veered into the lane of oncoming traffic and hit another car going 30-40 MPH. All of the airbags deployed and the car is totaled. She was taken to the local hospital for x-rays, but nothing was broken and she was released. We understand the driver of the other car is okay as well.
Immediately, my mind wandered from my own mortality being visualized on the computer screens to how Rosie’s accident could have been far, far worse – perhaps even fatal. I’m not sure exactly how I would have reacted to that news on top of my disease update, but I do know it would pale by comparison to my own situation.
On more than one occasion, Lorie and I have uttered the words “it could always be worse.” Lately, it has been harder and harder to make that statement. However, with Rosie largely unharmed in what could have been disastrous, today definitely could have been worse.
I will blog more about my condition and treatment options in future posts after digesting all of the information from the past 48-hours. In the meantime, with no infusion of M7824 today, we are on the train home to be with Rosie.
Earlier this week, Lorie and I made our biweekly visit to the National Institutes of Health (NIH) for my infusion of the experimental agent M7824. The two day trip was uneventful and included a variety of imaging and other diagnostic tests, including an ultrasound of my spleen and a chest x-ray to monitor the pleural effusion in my left lung.
Fortunately, all of the tests came back fine and I was cleared to receive my regular infusion of M7824. As with all the previous treatments, there were no adverse reactions and we returned home later that evening.
However, with the month of July rapidly approaching, I can’t help but start to feel quite anxious. This is due to the published results from Bristol-Myers Squibb’s “CheckMate 141” phase 3 trial with Opdivo® (nivolumab), an anti-programmed death 1 (PD-1) monoclonal antibody also known as a checkpoint inhibitor. In that study, 361 patients with recurrent squamous-cell carcinoma of the head and neck (SCCHN) whose disease had progressed within 6 months after platinum-based chemotherapy were assigned, in a 2:1 ratio, to receive Opdivo every 2 weeks or standard, single-agent systemic therapy (methotrexate, docetaxel, or cetuximab). The primary end point was overall survival.
Treatment with Opdivo resulted in longer overall survival than treatment with standard, single-agent therapy. The median overall survival was 7.5 months (95% confidence interval [CI], range 5.5 months to 9.1 months) in the Opdivo group versus 5.1 months (95% CI, 4.0 months to 6.0 months) in the group that received standard therapy.
Recall from prior posts that M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like, anti-PD-L1 antibody linked to two molecules of TGF-beta trap. Therefore, I always viewed M7824 as a “potentially” superior alternative to Opdivo given its added mechanism of action, hence my strong interest in participating in the M7824 clinical trial.
Assuming for a moment that M7824’s treatment effect is at least comparable to Opdivo, and considering that my disease recurred around December 2016, an expected survival of 7.5 months would translate to the July/August 2017 timeframe.
To be fair, an apples-to-apples comparison of Opdivo and M7824 isn’t possible. However, the results of Bristol-Myers Squibb’s “CheckMate 141” trial serve as a contemporary data set for checkpoint inhibitors in the treatment of recurrent SCCHN and are definitely something that I keep my eye on.
Barring any surprises, I’ll continue biweekly treatment with M7824 and then repeat imaging in July to see whether or not my disease has progressed. In the meantime, I’ll continue to savor simple moments like enjoying ice cream on a warm summer evening with my wife (see photo).
It’s been a couple of weeks since my last clinical post, so I wanted to provide an update following this week’s NIH appointments.
First, surgical insertion of my Aspira® drainage system has dramatically improved the pleural effusion in my left lung. It’s essentially a chest tube/catheter that allows me to drain the fluid buildup on an as-needed basis into drainage bags at home. The image to the right shows before and after chest x-ray images that demonstrate just how blocked my left lung was before being drained (nearly 2/3 blocked). It also shows how my left lung is now “close” to normal following drainage.
Second, I’ve been on prednisone (steroid) to help “sculpt” the inflammatory response, which is also helping keep the fluid from building up so quickly in my left lung. Whereas I was emptying 100 mL or more on a daily basis previously, I am now only draining 15-20 mL every other day or so.
Now that the pleural effusion can be managed, attention returned to whether or not to resume treatment with M7824, a completely novel, first-in-class, bispecific fusion protein (see prior posts for more details). My last infusion of M7824 was several weeks ago.
Following another CT scan and constructive discussion with the NIH team, we came to the conclusion that there is essentially a tug-of-war occurring between the cancer in my lungs and my body’s immune system, the latter of which appears to be benefiting from M7824. The hope is that eventually M7824 will tip the scale in favor of my body’s immune system and control the cancer.
Accordingly, the decision was made to keep moving forward with M7824 and I received an infusion on Tuesday, May 16, 2017. As with past administrations, there were no issues and I returned home to Pennsylvania with Lorie later that evening.
The pleural effusion will be monitored closely and managed via the catheter and steroids. As long as there are no major issues in terms of fluid in my lung, I will continue to receive an infusion of M7824 every other week. A repeat CT scan will be done in a month or so to reassess the situation.
This past Wednesday, I had a thoracentesis procedure in which a needle was inserted into the pleural space between my lungs and chest wall. This procedure was done to remove excess fluid, known as a pleural effusion, from the pleural space to help me breathe easier.
During the procedure, Dr. Elliot Levy, an interventional radiologists at NIH trained in radiology and minimally invasive procedures, drained 1.5 liters from the pleural space. Almost immediately, I felt better and even while I was being wheeled back to my recovery room, I asked my wife Lorie to grab me a turkey sandwich from the cafeteria as I was quite hungry. It’s possible the large amount of fluid on my left side was putting some pressure on my stomach, which could help explain why I haven’t had much of an appetite lately.
By Thursday, however, the fluid was returning, prompting yet another thoracentesis procedure on Friday to remove 1.5 liters of fluid. The rapid nature of the fluid buildup means that I will most likely have an Aspira® drainage system surgically installed to conveniently let me drain the fluid buildup at home via a small catheter and drainage bags. That procedure is planned for Monday, so I have been staying at NIH since Wednesday and will be here over the weekend.
More importantly, however, a CT scan was also done on Friday morning with disappointing results. The cancer nodules grew since the last CT scan on March 7, 2017. This reflects true disease progression as opposed to “pseudo-progression” as discussed in a prior post. I have been taken off the clinical study with M7824.
My individual results do not reflect poorly on the future of M7824, but rather underscore that we still have a lot to learn about immunotherapy and cancer. While I may not have benefited from the drug, the resulting knowledge and clinical data may help guide future development and I am proud to play a part in that process.
At this point, if I received no further treatment and went on hospice, my likely survival would be about two months – although every patient is different. I have scheduled an appointment with my oncologist at MSKCC to discuss the pros and cons of chemotherapy at this stage, but the balance between quality of life and quantity of life is not trivial and I haven’t made a firm decision to go in this direction. Chemotherapy may only add a month or two of survival with a negative impact on my quality of life.
While I have been very open about my disease since originally being diagnosed in December 2015 and enjoy blogging, I will now be focusing much more time with my wife and daughters and finishing up my memoir, which I hope to have published. This will unfortunately mean less time for updating this blog and responding to emails.
Thank you to everyone who has offered their best wishes, thoughts, and prayers during my cancer journey. Having such an amazing support network of family, friends, and social media contacts has been a great source of strength and inspiration. Special thanks to my wife, Lorie, who has been by my side the entire time.
If you’ll indulge me, I would like to end this post with three requests:
If you have a son or daughter, please talk to your doctor about the HPV vaccine, which protects against cancer of the cervix, vagina, and vulva in women; penis in men; and cancers of the anus and head/neck (including the base of the tongue and tonsils) in both men and women. HPV is a very common virus; nearly 80 million people are currently infected in the United States. About 14 million people, including teens, become infected with HPV each year, resulting in 30,700 cancers in men and women. HPV vaccination can prevent most of the cancers (about 28,000) from occurring.
Help preserve federal funding levels by communicating with lawmakers about the critical importance of investing in medical research. There are far too many people suffering from cancer and this is not the time to cut the budget for the National Institutes of Health (NIH) by 18.3 percent, about $5.8 billion, as has been proposed. In an Op Ed by Harold Varmus appearing in the New York Times on March 22, 2017, he states that only about 10 percent of the NIH’s budget supports the work of government scientists and that “over 80 percent of its resources are devoted to competitively reviewed biomedical research projects, training programs and science centers, affecting nearly every district in the country.” Harold Varmus, a professor at Weill Cornell Medicine and a co-recipient of the 1989 Nobel Prize in Physiology or Medicine, was the director of the National Institutes of Health from 1993 to 1999 and of the National Cancer Institute from 2010 to 2015.
If you or someone you know is battling cancer or another disease, please talk to a physician about available clinical trial options. Clinical trials are a key research tool for advancing medical knowledge and patient care. Such trials are important to learn whether or not a new approach works well in people and is safe and which treatments or strategies work best for certain illnesses or groups of people.
Draining the swamp is a metaphor used by American politicians, referencing actions to clean up government corruption. In my case, however, I’m referring to a treatment that involves draining the fluid from my chest cavity, either with a needle or a small tube inserted into the chest. This will treat my pleural effusion, also called “water on the lung,” which is an excessive buildup of fluid in the space between my lungs and chest cavity (see diagram).
The pleural effusion is likely the source of my coughing, shortness of breath, and other recent symptoms. I haven’t been feeling well at all lately, but once it is drained – I should feel much better.
Thin membranes, called pleura, cover the outside of the lungs and the inside of the chest cavity. There’s always a small amount of liquid within this lining to help lubricate the lungs as they expand within the chest during breathing. Certain medical conditions, such as malignancy, can cause a pleural effusion, which is likely my situation. The excess fluid prevents the lung from expanding normally.
Sometime this morning I will have the procedure and hope to provide updates when I am awake later on.
I may need this treatment more than once if fluid re-collects, but we’ll cross that bridge another time.
This is week #9 on clinical study, as I received my infusion of M7824 yesterday as planned. All of my pre-therapy vitals and bloodwork came back fine, which meant the treatment was a go. As with previous infusions, there were no issues during or after. Everything went just fine.
It was unfortunately a later night than expected, as Lorie and I just missed our 7:30pm train and had to catch one leaving the next hour. So, we ended up walking in the door at home around midnight. Could always be worse!
Following the discussion in my past few blog posts, I’ve been learning more about the concept of “pseudoprogression,” or the apparent growth of a tumor followed by sustained regression, which is common following treatment with checkpoint inhibitors. For example, I came across the video clip below by OncLiveTV that contains a discussion of “Pseudoprogression With Checkpoint Inhibitors in Non-Small Cell Lung Cancer,” where panelists explore the implications of this phenomenon for patients with NSCLC. While I do not have NSCLC, the overall concept of pseudoprogression with checkpoint inhibitors is relevant to my treatment and latest scan results – whereby the tumor growth exhibited could be from inflammation due to an ongoing positive immune response, or from an actual increase in the tumor that continues until the body’s immune system overpowers the cancer. It could also be a combination of the aforementioned. In any event, I think that pseudoprogression is an important concept for patients receiving some immunotherapies to better understand – especially when getting imaging results following treatment.
PS – anyone who knows me, knows that I’m a big Chicago Cubs baseball fan (having grown up in Chicago)…so I’d be remiss if I didn’t ask you to keep voting for retired catcher David Ross on this season’s ‘Dancing with the Stars’. In case you missed his debut performance, here’s a clip where he danced to Steve Goodman’s “Go Cubs Go” – while wearing Cubs gear.
As evidenced by the extensive discussions following my biopsy from last Friday, a tumor is indeed a very complex structure. It comprises cancer cells and stromal cells, tumor infiltrating cells—both cells of the immune system and cells not by convention being of the immune system, as well as an extracellular matrix mainly of proteins and carbohydrates.
Following my recent CT scan, the hope from obtaining core biopsies from one of my lung nodules was to get a better sense of the cancer at a cellular level, which may help shed some light on whether or not treatment with M7824, a completely novel, first-in-class, bispecific fusion protein is working (see prior posts for more details).
In particular, the presence of immune system cells (T cells, or T lymphocytes) in tumor biopsies and their potential impact on prognosis have been studied for decades. T cells are a type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections. Broadly speaking they can be divided into two different types, “killer” CD8-positive T-cells and “helper” CD4-positive T-cells. CD8-positive T cells are critical mediators of adaptive immunity. They include cytotoxic T cells, which are important for killing cancerous or virally infected cells, and CD8-positive suppressor T cells, which restrain certain types of immune response.
Despite contributions by other immune cell subsets, CD8-positive T cells have emerged as the predominant effector in most cancer immunotherapy settings¹. Accordingly, many immunotherapeutic strategies (including checkpoint inhibitors, such as anti-CTLA4, PD1, and PD-L1 antibodies) are dedicated to stimulating, enhancing and maintaining responses by tumor-reactive CD8-positive T-cells.
Favorable outcomes have been demonstrated in patients where high numbers of CD8-positive cells were found at the tumor site in patients with head and neck cancer, breast, colorectal cancer and also for others solid cancers. In one study, head and neck cancer patients whose tumors were densely infiltrated by CD3-positive and CD8-positive T cells had a significantly longer overall survival (OS) and progression-free survival (PFS) compared with patients whose tumors were poorly infiltrated².
While there seems to be a consensus that CD8 infiltration is a good prognostic marker in most malignancies analyzed, however, the impact of CD8-positive T cells on clinical outcome may differ and is difficult to quantify. Not only is the type of T cell important, but also its location, and moreover the specific phenotype and function of those cells in the particular environment.
Nonetheless, based on the preliminary results from my recent tumor biopsy and other factors, it appears that there is sufficient evidence of immune system activation in the vicinity of the tumor to indicate that the experimental agent M7824 may indeed be performing as we hoped. Accordingly, I am in 100% agreement with my doctor’s recommendation to continue on the therapy and will receive my next infusion this coming Tuesday at NIH. After a few more cycles of therapy, another CT scan will be taken in the future with the hope of demonstrating that the recent tumor growth was from treatment effect “pseudo-progression” rather than true disease progression, which has been previously described with immune checkpoint inhibitors like M7824.
¹ Targeting CD8+ T-cell tolerance for cancer immunotherapy. Stephanie R Jackson, Jinyun Yuan, and Ryan M Teague. Immunotherapy. 2014 Jul; 6(7): 833–852.
² Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer. P Balermpas, Y Michel, J Wagenblast, O Seitz, C Weiss, F Rödel, C Rödel and E Fokas. British Journal of Cancer (2014) 110, 501–509. doi:10.1038/bjc.2013.640
Following Tuesday’s news that several of the tumors in my lungs actually increased in size and a new spot appeared on my spleen, Lorie and I headed back to the NIH on Thursday for more tests to help better guide subsequent treatment decisions.
The first test was a CT image of my brain taken Thursday mid-afternoon, which would be used to rule out the spread of cancer to that particular organ. Patients with brain metastases are often excluded from clinical trials due to historically dismal survival and concerns about blood brain barrier drug penetration. Fortunately, we learned the next morning that this test came back negative for cancer progression to the brain.
The second test on Friday was an image-guided biopsy of a single lung nodule to help guide between cancer progression and inflammation as the reason for the increase in size seen on the recent CT scan on the lungs. In my case, a core needle biopsy was performed, which is less invasive than surgical biopsy and doesn’t require general anesthesia.
Early Friday morning, Dr. Elliot Levy, an interventional radiologists at NIH trained in radiology and minimally invasive procedures, met with us first to discuss the procedure. He pulled up a cross sectional image of my lungs, which showed several of the suspicious nodules.
One in particular was located in the pleural cavity – normally a thin membrane that lines the surface of the lungs and the inside of the chest wall outside the lungs. In the bottom of my left lung, however, fluid built up in the pleural cavity where one of the nodules was located. Dr. Levy explained to us how this nodule could be biopsied without puncturing the lung lobe, which can result in a longer hospital stay.
Sometimes, a collapsed lung (pneumothorax) occurs after a lung biopsy. As a precaution, a chest x-ray is taken after the procedure to check for this before sending the patient home.
After meeting with Dr. Levy, I was escorted back to the biopsy procedure room and placed on my right side on a table. I was consciously sedated, produced by the administration of two medications: a single dose of fentanyl given intravenously that can produce good analgesia for 20-45 minutes, and midazolam, which has a fast-acting, short-lived sedative effect when given intravenously, achieving sedation within one to five minutes and peaking within 30 minutes. The combination produces an altered level of consciousness that still allows a patient to respond to physical stimulation and verbal commands, and to maintain an unassisted airway. Midazolam is a primary choice for conscious sedation because it causes patients to have no recollection of the medical procedure.
Dr. Levy worked out of sight behind me to perform the biopsy, as he went through my back side. I was fairly nervous going into the procedure, but everything went extremely well with absolutely no pain or unexpected events due to the sedation.
After recovery, a subsequent chest x-ray confirmed that the lungs were indeed fine after the biopsy and we left NIH shortly thereafter to head back home to Pennsylvania.
The preliminary results from the biopsy should be available early this week. If the biopsy shows ample evidence of immune stimulation, an argument could be made to stay on the current drug and that the “pseudoprogression,” or the initial radiologic appearance of an increase in tumor burden, might actually be inflammation and followed by tumor regression. A remote possibility in my type of cancer, but worth confirming.
Should the biopsy results instead demonstrate increased tumor burden, then we could consider switching to another investigational agent or even chemotherapy to shrink the tumors before proceeding again with one of the immunotherapy clinical trials.
Determined to stay positive, Lorie and I took advantage of the warm spring day on Thursday to stop outside NIH and snap a picture in front of some cherry blossoms. Unfortunately, snow and cold returned on Friday for the commute home.
The results of today’s CT imaging procedure were not as we had hoped. Ideally, the dozen or so tumors in my lungs would have shown signs of shrinkage – indicating that the investigational drug was having a positive effect on the cancer. Instead, several of the tumors actually increased in size and a new spot even appeared in my spleen.
One of the hallmarks of immunotherapy, such as the checkpoint inhibitors, is the potential for a “delayed” response, which is not routinely seen with chemotherapy or other cytotoxic agents. Another biologic phenomenon unique to immunotherapy is “pseudoprogression,” or the initial radiologic appearance of an increase in tumor burden subsequently followed by tumor regression¹.
The CT imaging study cannot distinguish between cancer progression or inflammation as the reason for the increase in tumor size, so there is a chance that it’s due to inflammation and subsequent imaging tests in a month could demonstrate a reversal. However, it is also possible that the cancer isn’t responding to the investigational treatment.
To get more details, I’m undergoing a biopsy this Friday so that one of the lung tumors can be sampled. The preliminary information from that biopsy, which should be available next week, will help guide between cancer progression and inflammation. Decisions regarding how to proceed will depend on that outcome.
Needless to say, everyone’s hope was to have seen some sign of cancer regression on today’s CT scan and many teardrops were shed. The chances for a favorable outcome have diminished and must be acknowledged, but for now I’m persevering and will evaluate next steps following the biopsy results.
Sincere thanks to everyone who has offered their positive thoughts, prayers, and support. It is difficult to respond to each and every communication, but please know that I read “everything” and your time and effort is greatly appreciated. Special thanks to everyone at NIH for being so wonderful — even when faced with delivering bad news.
Now, more than ever, please keep all those positive vibes coming my way.
¹ Amidst the excitement: A cautionary tale of immunotherapy, pseudoprogression and head and neck squamous cell carcinoma. Baxi SS, Dunn LA, Burtness BA.
Oral Oncol. 2016 Nov;62:147-148. doi: 10.1016/j.oraloncology.2016.10.007. Epub 2016 Oct 21.
Monday evening, my wife Lorie and I traveled to Bethesda, MD in advance of my third infusion with M7824, a completely novel, first-in-class, bispecific fusion protein (see prior posts for more details). However, this was my first time being infused as an outpatient in the day hospital, as prior infusions required a short stay in the hospital for blood work, observation, etc. As with the first two infusions, everything went smoothly yesterday, with no adverse reactions during or following treatment. We caught a 9pm train home and were in bed by 12:30am ET.
As I posted on social media throughout the day while at the NIH, I was truly humbled by the outpour of support – especially hearing from people I haven’t seen in years or decades. Amid the sea of political rants and opinions via these channels, it was nice to be reminded that social media can be a positive experience. Throughout the emails, Tweets, and posts, a lot of people remarked that I sound and appear “surprisingly positive” and “happy.” And truth be told – they’re RIGHT.
Sure, I have advanced cancer – and I’m not Pollyanna about what the future may have in store for me as a result. But, I was very fortunate to participate in a clinical study with a quite promising, investigational immunotherapy that has, so far, had no negative impact on my day-to-day quality of life. That is a very stark contrast from what I experienced after going through chemoradiation. While the outcome is far from certain, participating in this clinical study has given me every reason to “hope” that the therapy will work. And it is that hope that gets me up in the morning…smiling…ready to face the new day.
If anything has changed recently, it has been for the better. I’m now focusing my existing time and energy where I want, and it has been liberating. Death is always knocking on our doors, but it isn’t until the sound becomes louder later in life that you discover new priorities and sense of urgency. In this regard, I’ve started writing my memoir covering a +20-year biotechnology career and have been working with an amazing editor. I always enjoyed writing blogs and newsletters, but Lorie strongly encouraged me to finally write a book and it has been quite rewarding thus far. My goal is to get it done by late summer or so (30,000 words so far…), and I will definitely let everyone know more details via this blog as the project advances. I also recently started a coffee table book project to showcase my photography work over the past few years, with approximately 200 images selected and a draft layout complete. To fund the latter, I plan on launching a KickStarter campaign to finish the design and secure a larger order to reduce the per unit cost. And most importantly, through my disease openness and this patient blog, I’m exploring numerous opportunities to help raise awareness for currently available vaccines that can protect boys and girls against human papillomavirus (HPV) subtypes that most commonly cause anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancers.
So, yes…I’m a cancer survivor and I’m positive because I have “hope” and will continue until life shows me otherwise. Inspired? Good…that’s my goal!
Finally, special thanks to everyone for the thoughts, gifts and support. Hearing from people I haven’t seen in years has also been amazing. A truly humbling experience and greatly appreciated.
It’s been two weeks since my last blog update, so I thought it was about time for a status report.
Earlier today I had my periodic clinic evaluation at the NIH following last Wednesday’s second infusion of M7824. Recall M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap (see prior posts for more details). At 22 days into this Phase 1 study, I’m still feeling good and haven’t experienced any side effects. Blood work, vitals, etc. all okay.
It was a quick roundtrip between home and the NIH today, which allows me to be back home to spend dinner with my Valentine, wife, best friend and birthday girl (ps – all the same person). Before I headed out for my appointment in the morning, we had a few minutes to exchange cards and snap a quick photo (see right).
I’m now done with the inpatient infusions for the study, so my next dose will be administered one week from today and I can go home afterwards. Here’s hoping for more, completely uneventful updates in the coming weeks!
Standing on the train platform this morning on my way to NYC, the late British rocker Joe Cocker’s version of Feelin’ Alright was playing over the sound system. Not only a good song to start the daily commute, it seemed an appropriate theme for this blog post.
It was exactly one week ago today that I received my first infusion of an experimental cancer immunotherapy agent, called M7824, as part of a Phase 1 clinical trial at the National Institutes of Health (NIH). Recall from my prior post that M7824 is a completely novel, first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap. While very early in the process, I’m happy to report that so far I’m feelin’ alright.
As someone who has received three cycles of chemotherapy and a total radiation dose of 70 Gray over seven weeks, I can say with conviction that, so far, being treated with an immunotherapy agent has been a proverbial walk in the park. In fact, if it weren’t for the fact that this clinical study is not placebo controlled, I would seriously question whether or not I was in the active arm of the study.
For example, in contrast to chemotherapy and radiation, I haven’t experienced any of the hallmarks of traditional cancer therapy, such as nausea or fatigue, with the experimental immunotherapy agent. Important to note, however, every drug has side effects and checkpoint inhibitors like M7824 are associated with their own unique spectrum of immune-related adverse events. These include dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. In some cases, these side effects can be managed with corticosteroids or diphenhydramine. Less frequently, clearly defined autoimmune systemic diseases, such as lupus, have been reported.
In fact, approximately 30-40% of patients treated with approved PD-1/PD-L1 checkpoint inhibitors (nivolumab/pembrolizumab) will have dermatologic complications. For most patients, dermatologic toxicity is the earliest immune-related adverse event experienced, with onset an average of 3.6 weeks after treatment initiation¹. Accordingly, it may be too early for me to be experiencing any such side effects.
Of course, having a “safe” drug is important – but for me, the real hope is that M7824 is effective in treating my recurrent disease. In this regard, in an interview with EP Vantage earlier this month, Luciano Rossetti, Merck KGaA’s head of R&D, told EP Vantage that M7824 is “the most exciting clinical asset in our pipeline right now” adding that it has yielded “spectacular” early data. You can read the full interview by clicking here.
I remain hopeful and strongly believe that my generation could be among the last to experience toxic upfront treatments like chemotherapy and radiation thanks to the many advances being made with immunotherapy.
First, my apologies for the length of time from my last clinical update. I’m not generally a superstitious person, but I wanted to wait for a few formalities to be addressed before posting.
Previously, I referenced that my next therapy would likely be at Memorial Sloan-Kettering Cancer Center (MSKCC) and include Opdivo® (nivolumab), a form of immunotherapy called a “checkpoint inhibitor.” What is that, you ask? Human cells carry certain proteins on their surface that enable them to escape attack from the body’s immune system. Some cancer cells wear one of those same proteins, called programmed death ligand 1 (PD-L1), which renders the cancer cells invisible to the body’s immune system. Blocking either PD-L1 or its receptor, programmed death 1 (PD-1), appear to be Achilles’ heels for multiple tumor types. Coincidentally, I covered the exciting early developments in the checkpoint inhibitor field in July 2013, which you can read by clicking here.
My concern is that across clinical studies in numerous cancer types, only about 20% of patients receiving checkpoint inhibitors have a durable response. For these patients, the benefits tend to last for years – perhaps even indefinitely. Exciting, yes. But for the other 80% of patients, the results are less dramatic. For example, in the recurrent head and neck cancer study for Opdivo, the median overall survival was 7.5 months for patients that received Opdivo versus 5.1 months for patients that received standard therapy options (cetuximab, methotrexate, or docetaxel). Clearly, Opdivo was superior to standard therapies and definitely worth considering. But the median overall survival is the time period lying at the midpoint of a frequency distribution of observed values, such that there is an equal probability of falling above or below it. The prospect of being in the 80% group with less than a year to live forced me to consider alternatives.
Fortunately, I became aware of a clinical trial for an investigational agent called M7824, a bifunctional fusion protein targeting PD-L1 and TGF-β, that was developed by EMD Serono, the biopharmaceutical division of Merck KGaA, Darmstadt, Germany. M7824 is currently being studied in a Phase 1 trial for patients with advanced solid tumors (ClinicalTrials.gov Identifier: NCT02517398). The principal investigator for the study is James L. Gulley, M.D., Ph.D., F.A.C.P. of the National Institutes of Health, Center for Cancer Research. In addition to his role as Chief of the Genitourinary Malignancies Branch, Dr. Gulley is also Director of the Medical Oncology Service, Office of the Clinical Director. He is an internationally recognized expert in cancer immunotherapy and I’ve had the honor of knowing him professionally for more than a decade – starting back when I was at Cytogen Corp (just an amazing individual and I cannot say enough good things about him!). Other key members of my fabulous team so far include Dr. Julius Strauss, Lead Associate Investigator for the study and Fellow Physician in Oncology at the National Institutes of Health, Andrea D. Burmeister, Physician Assistant, and Elizabeth Lamping RN, BSN, Research Nurse Specialist.
M7824 consists of a fully human monoclonal antibody against PD-L1 plus a transforming growth factor beta (TGF-β)-neutralizing trap component. This means that M7824 should confer all of the benefits of a checkpoint inhibitor against PD-L1, but with the added punch of neutralizing TGF-β. Dual targeting of the PD-L1 and TGF-β pathways makes sense because both are key immune evasion pathways with independent yet complementary functions.
The TGF-β signaling pathway is complex – resulting in either tumor suppressor or tumor-promoting activity depending on the cellular context in which the pathway is active. In advanced disease, the tumor suppressor arm of TGF-β signaling is lost and, instead, tumor cells proliferate. Further, TGF-β overexpression in advanced disease enhances tumor growth, suppresses the immune system, and exacerbates invasive and metastatic tumor cell behavior.
The more I researched TGF-β, the more encouraged I became about enrolling in the M7824 clinical trial – especially given the specific profile of my disease. Recall that I was diagnosed with human papillomavirus “HPV” positive, squamous cell carcinoma (SCC), which is cancer that begins from squamous cells, a type of skin cell. In addition to being one of the main types of skin cancer, cancers that involve the anus, cervix, head and neck, and vagina are also most often SCC.
Only a minority of people exposed to human papillomavirus develop HPV-related cancer, such as oropharyngeal cancer (lucky me!) or cervical cancer. In a paper published December 2014 in Cancer Research, Levovitz et al. demonstrated that genetic variation in immune-related genes is a determinant of susceptibility to oropharyngeal cancer and other HPV-associated cancers, particularly those related to TGF-β signaling. In other words, it is possible that people carrying genotypes with such variants are more likely to have an HPV-positive tumor compared to patients with the wild-type genotype. The likely functional significance of altered TGF-β signaling in HPV-related cancers is further supported by the finding by Levovitz et al. that TGF-β receptor type 1 is significantly overexpressed in both oropharyngeal cancer and cervical cancer.
In a paper published in February 2015 in Cell, Oshimori et al. establish a surprising non-genetic paradigm for TGF-β signaling in fueling heterogeneity in squamous cell carcinoma (SCC) stem cells, tumor characteristics, and drug resistance. Armed with this insight as well as the relevance for HPV-positive cancers, I decided to enroll in the study and passed the screening process.
In December 2016, Dr. Gulley presented preliminary data from the ongoing Phase 1 study of M7824 at the 28th symposium on Molecular Targets and Cancer Therapeutics, also known as the ENA symposium. Early results were encouraging, with M7824 associated with complete (CR) and partial responses (PR) in patients with advanced refractory cancer.
Today is my first one-hour infusion of M7824 and I look forward to reporting on my experience with immunotherapy in subsequent posts. With just a few minutes remaining for the infusion – so far, so good!
During today’s appointment with my oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC), we received disappointing news that the biopsy of my chest lymph node contained the same cancer cells (squamous cell carcinoma) as the original tumor in my tonsil. This means that the cancer has spread to distant sites and, unfortunately, cure is now no longer an option.
I was already familiar with the synergy between radiation and other forms of therapy, especially immunotherapy. Coincidentally, we were exploring such synergies back at Cytogen Corp with the company’s skeletal targeted radiotherapy being combined with a poxvirus vaccine being developed by Dr. James Gulley at the NIH at the time. Small world.
As the trial is randomized, I may or may not be one of the patients to receive the added radiation therapy. However, both arms of the trial receive Opdivo – so I get an active drug in recurrent head and neck cancer in either case.
There has been a great deal of enthusiasm for checkpoint inhibitor products, such as Opdivo. However, in the recurrent head and neck cancer study by Bristol-Myers Squibb, the median overall survival was 7.5 months for patients that got Opdivo. The other patients that received standard therapy options (cetuximab, methotrexate, or docetaxel) had a median overall survival of 5.1 months. True, there were some ~20% patients that had durable responses with Opdivo, but the vast majority (80%) did not have a durable response.
The good news is that Opdivo is a form of immunotherapy and doesn’t have many of the severe side effects associated with both chemotherapy and radiation. Accordingly, it is expected that I will be able to continue working and not have any major issues throughout treatment, as they are rare. However, Opdivo can cause your immune system to attack normal organs and tissues in many areas of your body, and can affect the way these organs work.
I’ll be posting more updates in the coming week or so…
Very long day, so I’ll keep this post brief. Lorie and I stayed overnight in NY yesterday due to the early procedure scheduled this morning at MSKCC. My appointment was at 9:15am and I was scheduled for the operation to start around 10:40am. However, my slot got delayed and I didn’t head into surgery until around 2pm!
The good news, if there is any, is that thoracic surgeon Dr. Park was able to get sufficient tissue from the suspicious lymph node via the bronchoscopyapproach and he didn’t need to do the surgical resection to go after the other nodules in my lungs.
The biopsy results will take a few days, but it is clear from the surgeon that the node they biopsied didn’t look “healthy.” Given that disease progression to the lungs is relatively common in advanced head and neck cancer, in my opinion the biopsy will most likely confirm spread of the original cancer to the lungs. Or, it could just be an unrelated new lung cancer just showing up now.
I hope to have more to report in the New Year but for now am relaxing in the passenger seat as Lorie drives us home. She’s such a trooper and I know my cancer returning isn’t easy for her.
Early this morning, I had my biopsy consultation with surgeon Dr. Bernard Park, deputy chief of clinical affairs, thoracic service at Memorial Sloan-Kettering Cancer Center in NYC. During the meeting, he presented the pros and cons for a couple of scenarios.
The first and most attractive option is a bronchoscopy, which is an outpatient procedure that allows a doctor to look at my airway through a thin viewing instrument called a bronchoscope. During the bronchoscopy, the doctor will remove tissue from a suspicious lymph node near my airway. If they can determine the presence of cancer during the procedure, then we are done with the biopsy portion.
The second option is a wedge resection, during which the doctor will remove a portion of my lung around one of the suspicious nodules that showed up on the PET scan. This is an inpatient procedure and may include several days in the hospital.
Dr. Park offered to combine the two options, where he will begin with the bronchoscopy and only do the wedge resection if necessary during the same procedure. This spares me from having to schedule two separate procedures and potentially delay results.
The biopsy procedure is scheduled with Dr. Park on Thursday, December 29th. Assuming the results are as expected, the next step is to meet with my oncologist Dr. David Pfister at MSKCC on Tuesday, January 10th, 2017.
As you can tell in the accompanying photo taken by my lovely wife, I’m so glad to be traveling back home on New Jersey Transit on the Friday before Christmas.
Of the +30 posts on this patient blog, this has been one of the hardest to write.
In the prior entry, I referenced that my next PET scan was scheduled for early February 2017. However, my radiation oncologist wanted to keep the PET scans consistent at six month intervals that resulted in moving the PET scan up to December 14 (last Wednesday). My prior PET scan was in June 2016.
Unfortunately, the latest PET scan did not contain good news. Multiple new spots consistent with malignancy showed up that were not visible six months ago. This includes activity in lung nodules, subcarinal/left hilar lymph nodes (near the trachea), and mild activity around the tonsils and in the region of the oral cavity. The results were confirmed by a subsequent CT scan this past Saturday.
In the world of medicine, however, cancer doesn’t exist until the abnormal cells are viewed under a microscope. Accordingly, I will soon need to have a biopsy taken from one or more of the suspicious areas highlighted on the PET scan. However, I don’t need to wait for that procedure and the subsequent results to know the outcome.
For head and neck squamous cell carcinoma (SCC), which was my initial diagnosis, pulmonary metastases are the most frequent and account for 66% of distant metastases¹. This information, combined with the imaging results, leaves very little chance that the biopsy results will be benign.
The consultation for the biopsy procedure has been scheduled for late this week and the actual biopsy procedure still needs to be scheduled. If the biopsy confirms that cancer has indeed spread to my lungs, the next step will be a meeting with my oncologist to discuss treatment options, which will likely include recent advances, such as biologic agents and immunotherapies (e.g., checkpoint inhibitors).
It’s that time of year again; where we get together with family and friends to celebrate the Thanksgiving holiday. It is also a time for reflection and appreciation, which has even greater meaning for me this year.
It was the day before the Thanksgiving holiday in 2015 when I first discovered a suspicious lump protruding from the right side of my neck. The formal diagnosis of Stage IV oropharyngeal cancer would occur several weeks later, but I knew at the time that the palpable growth just below my jaw line was anything but benign.
As a senior executive working in the field of biotechnology, and in particular the area of oncology, being diagnosed with cancer was difficult – but hearing “Stage 4” was especially disheartening. While staging systems are specific for each type of cancer, in general the cancer stage refers to the size and extent of the disease and is assigned a number from 1 to 4. If my cancer was confined to the right tonsil (where it started…) and hadn’t spread elsewhere, I would have been diagnosed with Stage 1 disease. Localized spreading would have been Stage 2 and depending on the extent of involvement of nearby lymph nodes – progress to Stage 3. When cancer has metastasized, or spread to other organs or throughout the body, it can be classified as Stage 4 and may also be called advanced or metastatic cancer. Stage 4 usually carries a grim prognosis compared to earlier stages of the disease.
Accordingly, when one is diagnosed with Stage 4 cancer, the immediate concern is whether or not the individual will be able to survive the disease. For me, however, the bigger concern was surviving the treatments and their side effects. In particular, my experience licensing and launching a product to treat oral mucositis made me very familiar with this debilitating side effect from both radiation and chemotherapy.
When reviewing treatment options with Dr. David Pfister, my medical oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC), I was really hoping that I would be a candidate for recent advances, such as biologic agents and immunotherapies. This was due to my familiarity with their targeted and less toxic profiles, especially when compared with chemotherapy and radiation. In fact, back in early April 2010 I published a 150-page industry report titled “Cancer Vaccine Therapies: Failures and Future Opportunities” and later that year held the inaugural “Cancer Immunotherapy: A Long-Awaited Reality” conference that took place at the New York Academy of Medicine in New York. For more information and background on immunotherapy, read “Insight: Training immune system to fight cancer comes of age” by Bill Berkrot of Reuters.
Unfortunately, approved targeted agents like Erbitux® (cetuximab) still require combination with radiation therapy and its associated side effects. Immunotherapies, such as Opdivo® (nivolumab) and Keytruda® (pembrolizumab) were only recently approved by the FDA to treat head and neck cancer, but their initial indications are limited to patients with disease progression during or after chemotherapy. I remain hopeful that use of these and other new agents will expand to newly-diagnosed patients going forward and that ultimately we no longer rely upon chemotherapy or radiation to treat this disease.
Nonetheless, it is encouraging to see two new drugs approved to treat head and neck cancer this year and know that there are options for me in the unfortunate event that my disease returns. In this regard, I was glad to help ring the Nasdaq Stock Market Opening Bell last month to celebrate cancer immunotherapy advances and the one-year listing anniversary of the Loncar Cancer Immunotherapy ETF (Ticker: CNCR). I first met Brad Loncar (@bradloncar on Twitter), Chief Executive Officer of Loncar Investments, at my inaugural cancer immunotherapy conference and he was kind enough to extend me an invitation to the Nasdaq event.
Ultimately, I went through seven weeks of daily radiation and three cycles of chemotherapy at the start of this year, which as actor Michael Douglas was quoted “somehow seemed very accurately mapped to the seven circles of hell.” In 2010, Michael Douglas was also diagnosed with Stage 4 oropharyngeal cancer and went through the same treatment regimen at MSKCC in New York.
So, while this year started off rough (understatement), I am extremely lucky and thankful to have no evidence of cancer following treatment and to finally be free of “most” of the debilitating side effects from therapy. For example, in recent months I have noticed a dramatic improvement in both energy level and saliva output and have started to reverse a 40-pound decline in weight I experienced during and after treatment.
Aside from eternal gratitude for my wife and daughters’ love and support throughout the process, I would like to extend a special thanks to all of the healthcare providers at MSKCC for their superb care. From my “dream team” consisting of medical oncologist Dr. David Pfister, radiation oncologist Dr. Nancy Lee, and surgeon Dr. Benjamin Roman to amazing nurse practitioner Nicole Leonhart and all of the others who cared for me. I wouldn’t be here today without you!
For my family, friends, and colleagues – too numerous to name – thank you again to EVERYONE that helped in some way…the thoughts, emails, prayer chains, food deliveries, financial support, hospital visits, etc. were all greatly appreciated.
My next PET scan is scheduled for early February 2017 and I hope to report that all remains clear around that time.
PS – as a native of Chicago and loyal fan, I am also thankful to have witnessed the Cubs baseball team winning the World Series for the first time in 108 years in 2016! Go Cubs Go!