First Chemo of 2018

Early this morning, my youngest daughter Megan and I arrived at Memorial Sloan-Kettering Cancer Center (MSKCC) to start round number seven of my current chemotherapy regimen (a combination of carboplatin and paclitaxel). What a fun way to welcome 2018!

Each treatment appointment is preceded by a blood test to look at the levels of various components (red blood cells, white blood cells, platelets, electrolytes, etc.). Not surprisingly, all of my counts were good enough to warrant treatment today as planned after a two-week break at the end of December 2017.

Michael and daughter Megan Becker in the chemo suite at MSKCC

Knowing today might be a bit crazy, I had scheduled an early morning appointment to try and get ahead of any delays. We arrived a few minutes before my 7:45am ET blood test and ended up catching the 12:20pm ET train from New York to return home. Everything went fine with treatment, although I don’t usually start feeling the side effects for a few days.

I met with my oncologist Dr. Pfister during today’s appointment. He discussed doing my next CT scan around the end of January 2018, which would be after the current chemo treatment cycle is finished. Depending on those results, he discussed maintenance treatment with just one of the two chemotherapies if the scan looks good. Otherwise, he might recommend switching to cetuximab (Erbitux©) if the chemo isn’t continuing to work. Either way, it looks like I’ll be coming to another key treatment decision point early in 2018.

The best news of the week was being able to spend New Year’s Eve celebrating with my wife, Lorie. Actually, “celebrating” might be a strong word–unless you expand the definition to include sitting on the couch watching Dick Clark’s New Year’s Rockin’ Eve with Ryan Seacrest and going to bed before midnight. But, we were together for yet another milestone. One that, frankly, I was quite surprised to see.

To my family, friends, colleagues, researchers, health care providers, members of the media and anyone reading this blog post–thank you for your interest in my cancer patient journey. I wouldn’t be here today without such a strong support network. Best wishes for good health, plenty of happiness, and much prosperity in 2018 and beyond to all of you!

 

Day Number Four in the Hospital

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.

X-ray image following drainage of 1.5 liters of fluid from left lung showing air returning to the top portion (red circle).

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.

Never Thought I’d Do It Again

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.

Starting treatment with the two chemotherapeutics (paclitaxel and carboplatin) on 7/18/17 at MSKCC

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…

Crossroads

It’s coincidental that after spending so many years leading a few small, oncology-focused biotechnology companies developing immunotherapies, radiopharmaceutical agents, and supportive care oncology products, I am now utilizing that experience, knowledge and network to make informed treatment decisions following my cancer diagnosis. Like driving down a familiar road, I am constantly seeing landmarks and signs that I know quite well from my time in the industry.

For example, some of the common side effects from chemotherapy and radiation therapy include oral mucositis (painful ulcers in the mucosa) and xerostomia (dry mouth). I studied these two side effects extensively as part of the due diligence process when I licensed and launched an advanced electrolyte solution called Caphosol® back in 2006. Based on this experience, I know what to expect from my chemoradiation treatment and hope to incorporate Caphosol into my arsenal against these debilitating side effects.

295077-smallWhile the streets may be familiar at times, I am still faced with difficult decisions at some of the crossroads. The latest example arose during yesterday’s follow-up visit with Dr. David Pfister, my medical oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC). Separate from my upcoming daily radiation treatments, the appointment largely focused on scheduling my three chemotherapy infusions and discussing what to expect in terms of side effects from the treatment. The chemotherapy I will receive is called cisplatin, which was first approved for use in testicular and ovarian cancers back in 1978.  The list of potential toxicities includes nausea, constipation, kidney issues, hearing issues, and others.  The conversation shifted to potential clinical trials and Dr. Pfister mentioned one that is exploring an alternative to chemotherapy that may have less side effects. In the study, the chemotherapy agent (cisplatin) is replaced by Erbitux® (cetuximab) – another FDA approved agent for treating head and neck cancer. Erbitux is an inhibitor of the epidermal growth factor receptor (EGFR), a receptor found on both normal and tumor cells that is important for cell growth. But the study also adds an investigational agent BYL719, which is an inhibitor of PI3K, an enzyme which fuels the growth of several types of cancer. Having worked at several companies developing inhibitors of the PI3K pathway, this was more familiar territory. However, trading the proven results with cisplatin for “potentially” similar efficacy with lower side effects from the investigational combination is a difficult crossroad.

On the one hand, the aforementioned clinical trial includes an approved agent for treating head and neck cancer (Erbitux).  This is different from some other clinical trial designs that include a placebo arm or an arm with only an investigational agent. However, Erbitux has its own side effects and there are unanswered questions in the medical community regarding whether or not Erbitux is “as good” as cisplatin. As a result some physicians only use Erbitux as a replacement for cisplatin when the patient cannot tolerate cisplatin’s toxicities. In my mind, forgoing cisplatin and its proven efficacy could jeopardize the potential for cure. Partially offsetting this risk is the inclusion of a promising new investigational agent – the PI3K inhibitor BYL719 being developed by Novartis. The PI3K pathway is widely known in the oncology community as a potential target for cancer therapy – and in particular head and neck cancer. Preclinical data suggest that simultaneous inhibition of PI3K and EGFR leads to synergistic antitumor activity in head and neck cancer, but future randomized trials are required to answer the question of whether or not the combination is equal to (or better than) cisplatin. Lastly, BYL719 is an investigational agent and although it appears well-tolerated in studies to date, side effects may arise as more and more patients are exposed to the drug.

Ultimately, I decided to stick with the more established cisplatin for a variety of reasons. First, it is my understanding that the radiation therapy, which would be included regardless of whether I opted for cisplatin or the investigational Erbitux/BYL719 combination, is the driving force for both cure AND debilitating side effects.  Most of cisplatin’s side effects, such as nausea, constipation, and other issues, can be partially offset with medication and hydration. Second, cisplatin has been around for decades and appears to be the gold standard in combination with radiation for Stage IV head and neck cancer and it is hard to argue with the clinical data supporting its use to date. Lastly, in the unfortunate event that my chemoradiation therapy isn’t effective – I can always explore investigational treatments as a next step.