Three Month Mark

Hard to believe, but later this week will be the three-month anniversary since I finished chemoradiation. Unfortunately, it’s also been nearly that long since my last blog post, although I did write a brief article for Cure Magazine published in April 2016 that can be viewed here.

I haven’t been writing much lately because I wanted this blog to be somewhat uplifting and inspirational. Frankly, the past few months have been extremely frustrating and difficult. It occurred to me, however, that sharing the bad along with the good may be equally important to others facing head and neck cancer. So here it goes…

In my last post from March 2016 I noted that my weight declined by 20 pounds since the start of chemoradiation. I’m now down a total of about 30 pounds (which I still think is okay since I was overweight to start). The additional weight loss comes from a combination of taste disturbances, reduced salivary output, and general loss of appetite during the period.

I’m pleased to report that my taste buds are now ~90% back to normal and that “most” foods taste the same as before therapy. Unfortunately, my saliva output is still greatly diminished and eating dry foods, such as bread, is very challenging. I have managed to eat a hamburger by taking off the top bun and eating the rest with a fork and knife along with a fair amount of ketchup. The biggest issue relates to a general lack of interest in eating, which I originally thought was due to the taste disturbances. Most days I have a high protein, nutritional shake for both breakfast and lunch and then a “normal” dinner and dessert. I haven’t been out to a restaurant since the start of therapy, as I am self-conscious about my eating habits.

Fatigue is still an issue, although it has improved over the past month or so. I returned to work full-time around mid-March, which meant getting up early and commuting to New York. Until recently, I would come home and literally pass out on the couch from exhaustion at the end of the day. Now I am able to stay awake through dinner, watch some television, and go to bed at a reasonable hour. I do still sleep on the morning train ride to New York and look forward to the weekends where I normally sleep until noon or later to catchup on rest.

The one major issue I haven’t discussed at length in this blog is the psychological impact of being a cancer survivor – namely depression. Societal expectations have taught men not to display any emotions. We are trained from an early age to be confident, stoic and strong. It is extremely difficult to fulfill this role or expectation as a male cancer survivor. On more than one occasion I have burst into an emotional crying session lasting a good 15-minutes. I’m not talking about the quiet episode of crying with sniffles and a tear or two down the side of your cheek. I mean full-fledged bawling your eyes out accompanied by nasal discharge and the near inability to speak normally – “I…I…I…nuh…na…nah…need…ah…uh…t…t…tis…tissue.”

The first such breakdown occurred around the start of chemoradiation when my wife and oldest daughter first came to my temporary apartment in New York. In retrospect, I had bottled up all of the emotion from first discovering the growth on my neck, to receiving a formal cancer diagnosis, to my first infusion of chemotherapy, etc. and let it all out at once. More recently, however, I broke down after showering the morning of my oldest daughter’s prom. I started to think about how happy I was to get home from New York during therapy to see my youngest daughter for her freshman formal and recalled the photographs from that evening with my neck visibly red from the radiation therapy. Then I started to think – are these going to be the last “big” events I will be around to see for each of my daughters? That spiraled into a series of awful “what if” questions that left me in a giant puddle.

Most of the time I am able to maintain a positive outlook and not let cancer “win” by occupying my every thought (insert ZOLOFT® ad here…). This is made harder by the requirement for periodic tests and imaging studies to determine whether or not the cancer has returned. Aside from those periodic tests, it feels like I am constantly watching over my shoulder for signs or symptoms of cancer’s return.

For example, in early May my wife noticed my voice had changed. At first she dismissed it as that froggy, lower tone you sometimes get first thing in the morning or when you have a head cold. But it didn’t go away and eventually even I noticed it. Subsequently, I found that the neck area under my chin was swollen. My first thought was “#@$&!” – the original cancer had now spread to the vocal cords, larynx (voice box), or other areas of the throat, as these would all be relevant symptoms. I saw my head and neck surgeon last week and he didn’t see anything suspicious upon visual examination. His initial diagnosis was that the voice change and neck swelling were simply the after-effects of radiation therapy, which can manifest even months after treatment. Nonetheless, he wanted to confer with both my medical oncologist and radiation oncologist to determine whether or not an imaging study is warranted. In the meantime, I’m trying to adjust to my new bass-baritone “Barry White” voice…which may or may not return to normal.

So that’s about it…you are now caught up on my life over the past few months. The next major event will be my PET scan on July 19, which will be the first such imaging test following treatment. Still hoping for a positive outcome from that study and will update as appropriate.

 

Progress Report

Yesterday marked the beginning of Week #3 for my chemoradiation treatment. By now, the cummulative effects of daily radiation have started to appear.  This includes oral mucositis (where the mucosal lining of the mouth breaks down forming ulcers) and xerostomia (dry mouth). The World Health Organization (WHO) Oral Toxicity Scale measures anatomical, symptomatic, and functional components of oral mucositis¹. The scale ranges from Grade 0 (no oral mucositis) to Grade 4 (unable to eat solid food or liquids). The majority of head and neck cancer patients (83%) who are receiving radiation therapy develop oral mucositis and 29% develop severe oral mucositis².

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Oral mucositis ulcer on side of tongue

My current assessment would be WHO Grade 2, which means that I can still eat solid foods despite the presence of ulcers (see photo of the single ulcer on the side of my tongue). Recall that I started taking Caphosol® at the start of my chemoradiation treatment. This oral rinse has been shown to reduce the severity and duration of oral mucositis in a clinical study. The study design used a different oral mucositis scale devised by the National Institute of Dental andCraniofacial Research (NIDCR), which ranks oral mucositis on a 0-5 scale where I would presently be at Grade 2 (single ulcer <1 cm). Results from the study demonstrated a peak Grade 1.38 for patients using Caphosol compared to Grade 2.41 for the placebo group. Accordingly, it will be interesting to see whether or not I develop additional ulcers or more severe oral mucositis to help determine the benefit of using Caphosol.

I received a progress report during my appointment with Dr. Nancy Lee, my radiation oncologist at Memorial Sloan-Kettering Cancer Center (MSKCC). The results are encouraging, as the tumor has markedly decreased in size over the first two weeks of therapy – characteristic for my type of cancer. The better news was that the PET imaging study looking at levels of oxygen deficiency (hypoxia) in the tumor tissue showed dramatic improvement. In particular, the pre-treatment scan showed “mild” radiotracer uptake in the primary tumor (right tonsil) and “intense” radiotracer uptake in the neck lymph node, indicating a significant amount of hypoxic tumor cells that are generally more resistant to radiation and many anticancer drugs. However, the most recent PET scan showed “no” radiotracer uptake in the primary tumor and only “mild” persistent uptake in the neck lymph node. Unfortunately, the fact that there is still some hypoxia means that they won’t be able to reduce the amount of radiation to the neck node, which could have reduced some of the side effects.

This morning I had my follow-up hearing test, which showed no change from pre-treatment.  This is also good news, as the chemotherapy (cisplatin) can sometimes cause hearing loss. Next week will be my second round of chemotherapy on both Monday and Tuesday. I’m hoping that this cycle will be less eventful than the first and that I don’t contract the flu or have any other surprises.

¹ World Health Organization. WHO Handbook for Reporting Results of Cancer Treatment. Geneva, Switzerland: World Health Organization; 1979:15-22.

² Vera-Llonch M, Oster G, Hagiwara M, Sonis S. Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma. Cancer. 2006;106:329–36.

Reunited

When I first licensed the North American marketing rights to Caphosol® in October 2006 (see press release), I had no idea that nearly a decade later I would be a customer. The product is intended to treat some of the common side effects from cancer chemotherapy and radiation – both oral mucositis (inflammation of the mucous membranes in the mouth with symptoms ranging from redness to severe ulcerations) and xerostomia (dry mouth). While these side effects can occur as a result of various treatments, they are particularly prevalent in head and neck cancer patients undergoing chemoradiation like me.

Michael Becker and the oral mucositis and xerostomia treatment Caphosol

Michael Becker reunited with the oral mucositis and xerostomia treatment Caphosol (click to enlarge)

It was disheartening that so many years after its commercial introduction, no physician I spoke with had heard of Caphosol. After a fair amount of nagging and discussion, I was finally able to secure a prescription this week and locate a pharmacy that carried the product in advance of starting treatment this Monday (special shout out to my wife, former colleague June, and her colleague Ken for their assistance in this regard!). This is important, as one the key clinical studies supporting Caphosol’s efficacy incorporated the product at the start of therapy.  In other words, Caphosol was used before the incidence of oral mucositis or xerostomia – as a preventative therapy. The trial demonstrated that Caphosol was able to reduce the severity of oral mucositis, decrease pain and associated use of opioid analgesics, and reduce the days of neutropenia (abnormally low concentration of white blood cells in the blood) – see journal abstract from the study.

To be perfectly clear – I have absolutely no financial interest in Caphosol. However, I am a believer in the product and did extensive due diligence as part of the licensing process. As a result, I hope that this blog post can help other patients at risk for oral mucositis and/or xerostomia learn about Caphosol. While there are other agents used in the treatment of oral mucositis and xerostomia, Caphosol is unique in that the product’s efficacy was demonstrated in a randomized, placebo-controlled clinical study. Perhaps the most significant distinguishing feature of Caphosol is the high concentrations of calcium and phosphate ions. Why is this important? Calcium ions play a crucial role in several aspects of the inflammatory process, the blood clotting cascade, and tissue repair, and phosphate ions may be a valuable supplemental source of phosphates for damaged mucosal surfaces. No other product on the U.S. market is formulated this way or has the proven clinical benefit that Caphosol does.

As you can see in the accompanying image, Caphosol is supplied in a carton with 30 doses.  A dose is comprised of two ampules of aqueous solutions, one containing a phosphate solution and the other containing the calcium solution.  The two solutions are combined in a glass and patients are instructed to swish the resulting mixture in the mouth thoroughly and then expectorate (spit out).  This process can be repeated 2-10 times per day, although four doses per day is what was used in the clinical trial.

I will report on my experience with Caphosol (good, bad, or indifferent) throughout my chemoradiation treatment over the next 6-7 weeks.  My first round of chemotherapy and radiation therapy starts this Monday and Tuesday.  As the treatments occupy most the day, it may not be until later this week that I post any blog updates.

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.