A Road Less Traveled...or, Looking for My Very Own Towel

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If you don't know where you are going, any road will take you there. ~ Lewis Carroll

I have never been part of the "in crowd".

Not in my school-aged years ... The nuns at the parochial school I was sentenced to would strike me on my backside or palms of my hands with a yard stick for having the audacity of questioning the unquestionable. The kids looked at me askew because of my oddity, fragility and grotesquely thin frame. A result after having spent nearly a year in a full-body cast after surviving being struck by a drunk driver, clocked doing 80 mph when he hit me. That, and my fascination with both the Kato character from the Green Hornet series (shame on Seth Rogen), and Barnabas Collins from Dark Shadows (anticipating Johnny Depp & Tim Burton's interpretation) set me apart.

Not in the teen years. ... In junior high I was the scrawny, underdeveloped, introvert. Quiet and studious. In high school, I stayed under the radar locking myself in the dance studio; writing for "above" and "underground" school newspapers; engaging in self-destructive introverted behavior as an alternative to "battling the adolescent beasties."

Not in the transition years when I opted, by default or circumstances, for a first "real boyfriend" who was seven years my senior. A boyfriend who was already the antithesis of who I wanted to become, and who ended up not being much of a boyfriend.

Not in the college years ... I was a late-start freshman, having taken time off between high school and college to work and earn money for tuition -- in an inhospitable Muslim country. I attended a very "preppy privileged" private university. Instead of being the cheerleader suggested by "boyfriend" I choreographed for a small modern dance troupe. Instead of living in dorms, I rented apartments in the surrounding gang-ridden neighborhood. Instead of joining the dominating "Greek" system, I worked 30 hours a week inputting horse racing stats into a computer program for a restaurateur / bookie racing enthusiast; and then as an editorial assistant for the Korean Consulate cultural magazine. In my spare time, I studied martial arts at night in the basement of the neglected PE building on campus; took skydiving lessons at Lake Elsinore; and would disappear to San Francisco - taking advantage of the $28 RT fare specials offered by PSA on their commuter flights between Burbank and SFO.

Neither in the law school years ... I started law school 5 months pregnant with my first child; attended a top tier law school, at night, so I could work for a DC law firm in the day to pay for tuition. Breast-fed while studying at any given hour - first child never slept between 7 p.m. and 1 a.m. Fulfilled my duties on as a Senior Editor on law review while confined to bed for 4 months with my high-risk second pregnancy (thankful for the cutting edge technology donated by the law firm...a laptop...this was 1991 and such technology was not available for general consumption).

Not in the "booster club" mom years with my two older children ... I was one of the few moms that was not living vicariously through their children, giving grief to the coaches because my child was not being doted upon as the next Olympic hopeful.

Even as a lawyer, I have been the odd-person out, pursuing "street-law" advocacy over more lucrative professional avenues. Much to the chagrin of my eldest child, and despite cutting my teeth on corporate civil litigation.

This reality has never bothered me.

And it came as no surprise to me that when I developed breast cancer, and didn't find out until the disease had already advanced to stage III, that I could not lock step with the well-developed Pink Brigade.

I agreed to the mastectomy. It was a visceral decision. The cancerous tumor was the only thing giving form, mass and shape to my left breast. I wanted it excised.

I then, however, opted out of everything else. All the cookie-cutter adjuvant treatments that I was besieged with -- offered up with icy portents of fear and dire statistics that if I didn't dive immediately into the toxic cocktails I would be accelerating the inevitable.

I dove instead into the less-chartered universe of naturopathic alternative treatments. Even in the alternative medicine world, most people I met and do meet pursue the naturopathic route only as a complementary addition to conventional adjuvant treatment (radiation and chemo) versus as a true alternative.

My treatment choices since my diagnosis in July 2009 have been very different than most. Certainly not "mainstream." And, yes, I sit here two years later having the invasive lobular carcinoma metastasize into my lymph nodes -- so I acknowledge that I fail the audition to be the poster child for "success." At the same time, I have been learning more regarding alternative medicine, and naturopathic doctors. There are a plethora of choices that I was not aware of previously (my then ND, however, should have known, shared, educated and pushed at me...but Dr. Daniel Rubin, I am trying to let go of my anger toward you <insert twitching eye and gritting toothy smile here>) and are now engaging.

At both stagings of this disease, the conventional medical community has provided me with only dire possibilities with little to nil positive outcomes. As such, it did not take me long to conclude that I deserved to explore other possibilities. After all, at the beginning of this journey the medical community was highly recommending aggressive chemo...despite an acknowledged 4% efficacy. Two years later with METS barking at my heals, the medical community highly recommended aggressive surgery and uber-aggressive radiation (no chemo this time...I guess once you drop under 4% possible efficacy even the med community throws in the towel on that option)...with an admitted only 20% potential for five-year survival if I lock-stepped. I am no mathematician, but gambler??? Hmmm....

If I am going to roll the dice I want better odds. Even if it places me back into the all-too-familiar position of being the oddity.

There has been a downfall to my choices, however. One that has been nagging at me more lately than before.

It is lonely out here on the less-travelled path.

I am used to being alone. I am comfortable (sometimes too comfortable) with alone-ness. But being alone is a different state than loneliness.

And the wisdom of Suzanne Somers is not the panacea I am craving. I have more faith in white mice and dolphins.

I do have access to a supportive blogging community. But even here, I am the odd-person out. I cannot commiserate with the devastating effects of chemo. I cannot commiserate with the hair loss; the lymphedema; the bloating; the chemo-brain. I cannot share dietary tips and recipes in battling the nausea. I cannot suggest topical relief for the inevitable skin damage from radiation treatments; nor hand-hold because I too have experienced the collateral weakening or damage to other organs as a result of the radiation. I cannot laugh and offer alternative "beauty" tips on how to fashionably conceal hair patches and baldness. I cannot offer or seek guidance as what to expect from the "next step."

I have no one to empathize with, no one who has dealt with my particular experiences on this alternative roadway. I have searched and posted on varied cancer support sites. Looking for someone who has or is walking a similar treatment path.

The universe is silent.

I have yet to find a fellow traveler who understands my reference to the "rumbling dryer" sounds that permeate by head when hooked up to a high dose vitamin C IV. The uncontrollable shaking. The "spaciness." The taste of the vitamin C within minutes of hitting my veins. The frontal headache and dry heaves. The ache and fatigue that washes over me for the remainder of the day after a treatment.

No one to bounce concerns off of ... is it a reaction to the supplements or indications of disease progression? Do they feel the same daily fatigue? Do they feel the same aches, crunches, pains? Have they felt the restless lethargy that I battle? Do they too get so very tired of the regimen, the scheduling, having to write all your own warning labels?

No one else to b*tch with as to people's reactions and responses: "But you look good...." "You would never know...." "You think you are tired...."  "At least you have your hair .... "

Would I make different choices, now that I have been on this path for over two years? Travel the more defined roadway? A roadway that sadly is becoming a congested highway as our society becomes more "advanced"?

Absolutely not.

I am too much of a coward to travel the conventional adjuvant highway. I studied that dog-eared road atlas and found it far too harrowing. I do not have the mindset.

But alas, even the Hitchhiker had his towel. A comforting and useful object. At this juncture, most days I feel that I just need my own towel.

A towel, it says, is about the most massively useful thing an interstellar hitchhiker can have. Partly it has great practical value - you can wrap it around you for warmth as you bound across the cold moons of Jaglan Beta; you can lie on it on the brilliant marble-sanded beaches of Santraginus V, inhaling the heady sea vapours; you can sleep under it beneath the stars which shine so redly on the desert world of Kakrafoon; use it to sail a mini raft down the slow heavy river Moth; wet it for use in hand-to- hand-combat; wrap it round your head to ward off noxious fumes or to avoid the gaze of the Ravenous Bugblatter Beast of Traal (a mindboggingly stupid animal, it assumes that if you can't see it, it can't see you - daft as a bush, but very ravenous); you can wave your towel in emergencies as a distress signal, and of course dry yourself off with it if it still seems to be clean enough.

More importantly, a towel has immense psychological value. For some reason, if a strag (strag: non-hitch hiker) discovers that a hitch hiker has his towel with him, he will automatically assume that he is also in possession of a toothbrush, face flannel, soap, tin of biscuits, flask, compass, map, ball of string, gnat spray, wet weather gear, space suit etc., etc. Furthermore, the strag will then happily lend the hitch hiker any of these or a dozen other items that the hitch hiker might accidentally have 'lost'. What the strag will think is that any man who can hitch the length and breadth of the galaxy, rough it, slum it, struggle against terrible odds, win through, and still knows where his towel is is clearly a [person] to be reckoned with. ~ Douglas Adams

"What is important to you"?

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I have been hearing...and listening...to a great deal of frustration from friends and family. My cancer journey is confusing and scary for them, understandably. Equally understandable is their frustration and confusion as to my choices in treatment and management of what has now evolved into a chronic disease. I am trying to address each of those I love and care about individually. To reassure. To help them, if not understand, to at least accept. Below is a compilation of several letters that I have written to some of my loved ones. I share them here, first, because this is where I process my cancer journey. Second, because I hope that through the venue of my blog understanding and/or acceptance will come. I have to hope. WARNING: Content May Contain Concepts of Emotional Sappiness.

Dear Loved One:

I am going to start this letter with the single most important message I wish for you to take away, and that is that I love you!

Also, you need to know that you are important to me, and I am listening very closely to your concerns. I know that you are worried. I feel deeply and appreciate your concerns...truly. 

   

I know that the prevalence of pink & pretty media coverage regarding breast cancer makes it seem that great leaps and bounds in treatment options are available. I also know, from experience, that when Susan B. Komen and their ilk speak about "cures" and "awareness" they are speaking only of early stage breast cancer. That is, breast cancer that is confined to the mammary glands, and which can be "curable" but only to a certain extent. Susan G. Komen is not about advanced stage breast cancer.

My cancer was initially discovered when it was already late-stage; and is of an infiltrating / invasive nature. Remember, this was despite years of mammos misidentifying the tumor growth solely as fibrous breast tissue. When breast cancer has metastasized, i.e., moved out of the mammaries, treatment options are few and most are longshots in achieving a positive prognosis. Regardless, I have not been sitting idly. Nor, should you presume that I am acquiescing, giving in, admitting defeat, etc. to a chronic disease.

Yes, it is true that the MD community is a bit pessimistic about my situation - save, interestingly, my oncologist who is excitedly on-board with my current protocol. Well, maybe not excited per se, but at least supportive. You must trust me, I have researched and continue to research extensively my current treatment plan. The MD community (save for my oncologist) would like to go "full guns" and "aggressive beyond measure" (these words from the radiation onc). And, according to same radiation onc, going "full guns" will only give me a 20% chance at a 5 year survival. You must remember: there is a vast difference between survival and living.  

The surgical onc clearly does not want to do the surgical "full guns" and "aggressive beyond measure" surgery -- a full axillary nodal dissection. Why?  Because  it is "messy" trying to avoid all the clusters of nerves, blood vessels, and arteries. And, she acknowledges that there is no difference in the 5 year morbidity with women who have had a full axillary nodal dissection, and those who don't. She does, however, give me a 25-30% likelihood of long term nerve damage.

I cannot articulate the appreciation I feel for you own efforts in researching treatment alternatives for me. Your own stubbornness and deep caring are two of your endearing qualities. I also appreciate the emotional difficulty you are having in sharing your research findings with me. Nothing about cancer is easy. Unfortunately, your research brought nothing new or surprising. I was aware of the challenges with my prognosis. Rightly or wrongly, I did not feel that I should dump all of the "lovely" news on you in one dose. It wouldn't be fair to you or me. Why? Because I am still coming to terms with what the medical community is saying to me. I am not prepared, yet, to be a strong shoulder for you while I answer your questions. Selfish, yes. And unapologetically so. I am getting good at being selfish these days. 

As I shared with you, the radiation oncologist here in Arizona -- who, btw is touted as the "go-to radio-onc" (imagine me raising an eyebrow of doubt) was not as forthcoming as the one you communicated with. Radio onc's 20% chance of a 5 year survival was predicated on me first going through the surgical "debulking," followed by an aggressive protocol of  "clean up" with broad-based radiation of the neck, shoulders, axillary and chest wall.

I asked radio-onc how long after such intense radiation exposure would my body begin to show signs of damage to my heart and lungs (predictably leading to heart and pulmonary failure). She would not answer.

My individual situation...my reality that I have to live with, is that I must continue with life-as-is. I am fortunate that my work is something that stirs my soul, because my working is a direct and palpable benefit to my family. Family is what is important to me. Indeed my kids come first. I will never be selfish when it comes to their immediate and long term futures. Each and every decision that I have made over the last 25 years has been about family and building a life and future for my children.

I will also not allow this chronic illness to turn my family into another "recession statistic" -- funneling funds into a medical industry that holds no hope for me. I secured Husband's agreement on that one. What that means is that I will not hurt my family financially while chasing medical pipe dreams. The decisions and treatment protocols I have decided upon (with, again, the surprising support of my medical onc) are to help me manage my chronic illness and still have a quality of life with my children, now. 

I can honestly say, I am feeling better this week - week 3 of my protocol. I do "suffer" immense nausea and fatigue after the high dose vitamin c IVs, but it passes within an hour or two with the help of lime slushies.

You will have to trust me. Your trusting me is important.
The health (emotional and physical) of my children are important to me.
Making sure my children have a competitive edge and a fighting chance in this world that seems like it is being turned on its head is important to me.
Being strong for my children, while I can and when they need me now, is important to me.

Dear-heart, we are all going to die at some point, no? That is the life-cycle. It is also very possible that the cancer may not be what kills me. It is as likely that a reckless driver on the interstate, or the space debris currently falling to earth is is what causes my death. Old age may be what finally takes me. The point is, none of us know with any certainty how we will die...only that we will.  Because of a bizarre turn of events, I am "fortunate" to have (potentially) prophetic knowledge of my demise. Embracing my mortality on a daily basis does color my daily responses and perceptions. 

What is important to me is that the time I am here is spent with meaning and with as many quality moments with those that I love. Giving up sitting on the sidelines at my son's soccer practice, so I can chase a possible treatment far away from him, pales in comparison. Attending my son's concerts; making his lunch in the morning while quizzing him on science vocab or math problems; reading with him at night snuggled in his bed together -- I would never make a choice that would steal those moments away from me, now. These moments cannot be recovered, and are real now. The future, under the best of circumstances is unpredictable. 

Not being able to have my girls reach out and share with  me all of their daily joys and sorrows (18x a day -- really!) would decimate me emotionally. Being a sounding board for the volatility of their developing adult-hoods is the reward of parenthood. My girls are growing up, now.  And there is Husband. He has been my BFF and "work in progress" for 25 years now - and I have not finished with him as yet! He is not getting out of this marriage that easily, especially when he is yet to be housebroken.

Missing all of this while I am here in the moment feeling strong and relatively healthy, well, that would kill my spirit long before my body would crumble.

~TC

To DCA or Not DCA...That is the Burning Question

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Dr. "DCA"

Dr. Evangelos Michelakis 
Professor of Medicine, Vice-Chair of Research Department of Medicine, University of Alberta

Researcher of the month:

Nov 2010

Science excels in challenging traditional ways of thought. Dr. Evangelos Michelakis is an apt disciple – a medical researcher who shines at confronting scientific and clinical dogma to benefit medical progress.
His work straddles two seemingly unrelated fields, pulmonary hypertension and cancer, which have “more in common than you think,” he says. His pioneering work has contributed to emerging paradigms in both fields and lent credence to an 80-year-old theory of German biochemist Otto Warburg, who believed that the metabolic shift in cellular energy production that occurs within abnormal cells, now called the “Warburg effect”, is a cause – not effect – of cancer.

Tackling traditional thought

In 2001, Dr. Michelakis and colleagues at the University of Alberta began a series of laboratory experiments that led to important discoveries and innovative ways of thinking about pulmonary arterial hypertension (PAH). This rare but deadly disease afflicts women in the 30s and 40s whose 5-year survival rate is worse than for metastatic breast cancer.

They studied the effects of sildenafil (Viagra®) on PAH. This work led to a small clinical trial that showed, for the first time, that this drug is a safe, effective treatment for patients with PAH. The Heart & Stroke Foundation of Canada funded this groundbreaking work, which led to further studies by the drug’s manufacturer, Pfizer, and a new formulation of sildenafil (Revatio®) to treat PAH.

Dr. Michelakis and coworkers were also first to show that a cancer marker called survivin, which was thought to be found only in cancer cells, is heavily expressed in abnormal pulmonary arteries. This work, published in the Journal of Clinical Investigation (JCO), was one of the first comprehensive studies to show a link between PAH and cancer.

One discovery led to another. While investigated excessive cell growth in the walls of pulmonary arteries, Michelakis and his team discovered that the cellular powerhouse – mitochondria – in lung vessels differs from those in other arteries.

The mitochondria play several vital roles within cells. They generate energy, in the form of ATP, by oxidative phosphorylation – the combustion of glucose and other fuels by oxygen. They also act as oxygen sensors and control programmed cell death. This process, known as apoptosis, is suppressed in PAH – and cancer. Both diseases, Michelakis notes, are characterized by uncontrolled cell growth.
He and his team began to search for a drug that would target the mitochondria of pulmonary arteries to reinstate apoptosis. They came upon a substance called dichloroacetate (DCA). This small-molecule drug has long been used to treat congenital mitochondrial abnormalities – for so long, in fact, that it no longer has patent protection.

“We showed that the mitochondria in PAH cells in both animals and humans were suppressed. When we gave DCA, these mitochondria became active again. Apoptosis, which requires functional mitochondria, was reactivated, and abnormal cells within the walls of pulmonary arteries started dying, opening up the lumen and improving PAH.”

DCA works like a molecular scalpel, he explains, targeting abnormally growing cells in PAH without affecting normal cells in other arteries, which do not share the same mitochondrial changes.
This work was published in Circulation (2002, 2006), Circulation Research (2004), PNAS (2007), and Science Translational Medicine (August 2010).

Breathing new life into old theories

In 2007, Dr. Michelakis and colleagues published evidence from laboratory studies in Cancer Cell that showed mitochrondria are suppressed in cancer. They then showed that DCA could reactivate the mitochondria and reinstate apoptosis.

Their findings had a major impact. For the first time, there was proof that cancer actively suppresses the mitochondria to foster abnormal cell growth. This evidence challenged the prevailing dogma, which suggests that cancer is a disease of mutated genes, not a consequence of abnormal metabolism – and it reactivated an interest in Warburg’s belief that abnormal mitochondrial function is a cause, not effect, of cancer.

“The timing was right,” says Michelakis, “because the metabolic theory of cancer was being born.”
DCA inhibits a mitochondrial enzyme called pyruvate dehydrogenase kinase (PDK). This key enzyme is overexpressed in cancer cells. PDK deactivates the pyruvate dehydrogenase (PDH) complex of enzymes on the outer mitochondrial membrane. The PDH complex acts as a gatekeeper that controls the flow of glucose and other fuel into the mitochondrial powerhouse. Without fuel, the Krebs’ cycle cannot function and glucose oxidation does not occur. Apoptosis is shut down.

As a result, cancerous cells suck in more glucose to use in glycolysis – the anaerobic conversion of glucose into energy outside the mitochondria. By shutting down the powerhouse, they cannot produce energy as efficiently but, with apoptosis switched off, they no longer die. Eventually, the uptake of glucose increases to a point that fulfills energy requirements, while the mitochondria remain inactive.
DCA reverses this chain of events. It suppresses PDK and liberates the PDH complex. The mitochondria can resume normal functions, including apoptosis.

Since DCA has been used in the treatment of children with congenital mitochondrial abnormalities since the 1960s, it has a well-known safety profile. With no patent protection, it is an inexpensive medication.

The long, winding road to human trials

Without industry support, it is difficult to advance promising drugs from animal to human trials, says Michelakis. Since DCA had no patent protection, industry was not interested in funding clinical trials.
After fundraising, Michelakis began phase I trials of DCA in small numbers of patients with metastatic cancers at Alberta’s Cross Cancer Institute (CCI). The University of Alberta agreed to cover indemnity which is usually covered by industry sponsors. The Alberta Health Sciences also helped with a number of in-kind contributions. Then, with the cooperation and encouragement of the Director of Neurosurgery Kenneth Petruk, Michelakis’ team zeroed in on one cancer – glioblastoma multiforme (GM), a highly lethal form of brain cancer.

They conducted a clinical trial in a small number of patients with GM. Tissue samples from before and after DCA treatment showed that the small-molecule drug was making a difference.

“We showed that DCA was inhibiting PDK and activated PDH in the tumors of these patients,” says Michelakis. “There was actually some evidence of tumour stability or even regression.”

The results, published earlier this year in Science Translational Medicine (May 2010), once again rocked the scientific community. In addition to challenging scientific dogma about mitochondrial function in cancer, it showed that researchers could conduct human clinical trials without industry support.

The study has opened the door to further DCA trials. Michelakis’ team plans to conduct joint studies of DCA in breast, lung and brain cancer and PAH with several international centers, including UCLA medical school, Memorial Sloan Kettering Cancer Center, and Imperial College in London, UK.

The route less traveled

The biggest challenge in investigating promising small molecules is not learning to think outside the box, says Michelakis, but finding ways to overcome the obstacles that discourage researchers from performing human trials without industry support.

DCA is not a miracle drug, he says, but “it’s very important, because it has helped us to find a new direction. It is pointing the way to the development of better mitochondrial-activating drugs. There’s no question about it.”