“First line”, two words that implicate the potential of a “second line”.

It conveys a manner of description that anticipates a backup plan, and possibly a backup to the backup.  As cancer metastasizes, what would be an appropriate visualization?  Is it a movie like scene of attackers eviscerating the first line of defenses, the lymph nodes?  Or a subversive and multi-regional coup d’état by cells gone rouge?

Is this simply manifested imagery from the random disquiet of my mind?

In today’s theatre of incurable advanced breast cancer, where the destiny of all the cellular changes that ravage within a body is foretold, what is “treatment”?  What are the parameters by which therapy is chosen for introduction?  To befuddle mutating clone armies and gain time?  Or is it to control the speed of how ravaged and war-torn the landscape gets?  And how would the treatment itself decimate the landscape and environment, which provide life to the host?

Can the afflicted, within whom these scenes play out, have both the option of maintaining quality of life and prolonging overall survival?

“You look good!” greeted Dr L, the neurosurgeon.  Annie definitely shows more energy this week.  We were a half hour early, but the front desk did not actually check her in.  Annie was the alert one who noticed that someone else’s name, in hangul, showed up on the electronic “who’s next” board, someone who was after her on the posted printout of the day’s patients.  If not for her alertness, we might have just waited perpetually.  We had a good chat with the neurosurgeon about how she’s doing, the potential for future recurrences of cord compression, additional symptoms to watch out for, and when he would order follow-up scans to see how things in the spine may have changed from radiation.  He gave a friendly laugh when we eagerly asked about physical therapy and exercise that she could do to avoid muscle atrophy.   He asked us to wait till the scans, past the window of time where the vertebrae themselves were weakened from radiation.  Eight weeks after the end of radiation, so mid-October.

And then it was off to see Dr P, the oncologist.  It was time to find out what the pathology report would contain regarding the prior week’s biopsy.

Feeling like a student again, I mentally reviewed all the typical combinations and decision graphs mentally, of what were typical treatments for different scenarios, and the relevant recent trial approvals and developments.  Annie and I had reviewed the prior night as well.  Yes the past two weeks of my evenings were filled with reading material, like NCCN and UpToDate standard of care treatments; silly or not.  There’s even a book called Pocket Oncology.  A cheat sheet of sorts for medical students, and a possible nuisance maker for doctors in the hands of the untrained like me.  There was some eagerness, some trepidation, some fear.  Eagerness to proceed, trepidation of a difficult-to-treat cancer sub-type, fear that we were not prepared.

Among lessons learnt from her past two walks with cancer, one is if you enter the initial conversation about conventional therapy unprepared, the names of the drugs alone will overwhelm your mind, leaving you little capacity for any clarity with decisions or meaningful questions.  Audio recording for review or not.  Faced with more complexity than the mind might want to critically think about under the pressure of time, among other pressures, thoughts can get hazy.  And as the internet will reveal, when faced with such complexity, avoidance is gratifying and patients can easily be drawn to attach themselves to simpler arcs of cancer quackery, like juicing raw calf liver; or something more palatable, like orange juice.  I desire to deeply understand options we encounter.  Futile or pointless, one may argue.  But a desire nevertheless.

A doctor with patience might attempt to simplify to the unprepared, which ultimately leads to reductionism.  I do not envy the job of a good oncologist (or any doctor for that matter).  Or should the patient leave the choice, which might be a choice among multiple choices, purely to the doctor?  Doctors are human too, and I respect the incredible depth of character required to be able to maintain emphatic listening over a busy day.  But to make such choices tailored to an individual versus a routine plan, in a span of minutes, when there is no true “fix”?  The routine plan wins in general, I would wager, as much as our idealistic desires expect us to be our doctor’s sole patient.  And the default routine might not be the choice for you.  Perhaps it was the experience of having a top rated doctor, perhaps more interested in other research, who saw your wife’s second little regional occurrence as an inconvenience to her day, who dealt her a potentially flippant plan.  One which leaves other doctors today curious, as to why no further investigation or adjuvant therapy was done.  We’ve been fortunate to now have as good a doctor as we think she is, and one that we like.  One that shows empathy despite language barriers.  So given the tireless workload the doctors seem to carry at this cancer center, the least I could do was to be prepared to listen well; and take responsibility in conversations with her, instead of tangential questions like, “How about orange juice?”

We were called into the room to await Dr P, the oncologist, and I resisted the itch to walk over to the pathology report screen to peek.  The incredibly efficient set up for the doctors here tend to be as follows.  They consult in two adjacent rooms.  While they are in one, nurses set up the other room for the next consult.  Desks neatly back to some determined layout, coffee refilled, and patients’ charts pulled up on 4, yes four, 21-inch monitors.  Two vertically oriented ones showing imaging, the third with patient summaries, and the fourth for notes and the latest lab report.

What did the small print read?

“You look good.” echoed Dr P, smiling at Annie as she sat down.

After a quick follow up on current symptoms, she went straight to the biopsy results.  ER+(8), PR+(4), Her2-, Ki-67 30%.  The Ki-67 puts the subtype currently into luminal B (her2-).  She articulated that it was a good report, in the sense that it would allow us the options of endocrine therapy.  She proceeded to discuss implications and options, in a partnership manner, like she said she would in earlier consults; even if the options were of a rather standard protocol, given the biopsy.  It came to choices of goserelin plus an aromatase inhibitor (letrozole), goserelin plus a hormonal drug (fulvestrant, a SERD), oral chemotharapy (capecitabine), or some clinical trial.  The goserelin is effectively used to put a pre menopausal woman into a post menopausal state.

We’d rather not start with chemo, and she agreed.  So it was one of the first two.  Her experience with breast cancer in younger women inclined her towards the second.  There was a pause, and we asked her about adding palbociclib to the fulvestrant.  The combination was recently fast track approved by the FDA in the USA after the PALOMA3 trial, which included pre/peri menopausal women, and showed a median doubling of progression free survival.  “Ah!” she smiled.  Turns out, Korea was one of the countries that had participated in the trial, and Dr P had patients in the trial.  It had just been approved for use in Korea, two days prior to our consult.  She briefed us about the experiences she’s had with patients on it, and possible dose adjustments needed for Asian women.  There was one small catch.  The drug was not yet in circulation in Korea outside of the trial.

Initiative and action took effect. She talked to the nurse, and picked up her cell phone right then; calling hospital administration, who sent someone over; and also called a contact at Pfizer Korea directly about it.  And told us if we could wait, she’d let us know about getting the drug in.  We covered other questions we had around goserelin (Zoladex) dosing; and the bisphosphonates she would continue with versus denosumab.  The hospital has its own genome institute, so she would also be sending tissue for genome sequencing.  We went back outside to wait as she completed the rest of her day’s consults.  The corridor still filled to capacity with patients.  We had a dinner appointment at 7pm with A (KP’s wife), who was in Seoul for work from Singapore.  KP had visited a few weeks ago.  7pm had initially seemed like a reasonable time to plan dinner, given that 2:30pm was the last appointment we had.

Two hours later, we saw Dr P again, probably as the last patient of the day.  She was kind to note, “You waited a long time.”  The hospital will attempt to work with Pfizer Korea to expedite bringing the drug in, within 3 weeks, from wherever stock is available, either US or Germany.  The timing actually works out, she noted, for Annie to start goserelin and fulvestrant first.  This allowed for the second radiation of the spine (C7-T1) to begin and complete before palbociclib in added.  Annie and Dr P had a moment of between them, commiserating the size of the Zoladex shot and counting the total number of shots she’d be getting monthly, starting that very day (fulvestrant was two shots).  You never really forget the size of a Zoladex needle after seeing one in person.

It was nearing 6pm, when outpatient departments close, as we left her office.  We had order sheets for pain meds at the pharmacy to pick up, and for the shots to be done.  Frenzy ensues.  Nurse J from the international health clinic happened to come by to pass us printouts of blood tests as well.  Timely.  It was helpful for me to have her navigating the pharmacy process before close.  Simultaneously, Annie went into another room to get instructions about her shots and sign acknowledgements.  Nurse J headed off after helping me, and I walked back to find Annie, quietly relieved that our friend A had sent a message to indicate that she would be late to meeting us for dinner.

Complications arise.  If only things would always “just work”.  Being the foreigners, and being the first to get a particular medication at the institution probably messed with standard processes somewhat.  Turns out the nurse in charge of the paperwork for the various drugs was not fully in sync with Doc’s suggested process for the palbociclib.  The form she prepared for Annie to sign was for ordering it through the Korean government’s Rare Medications center.  Which requires a bank transfer upfront prior order, with the center dong the order after.  This would become a monthly bank transfer, to a government agency, without an invoice/receipt, at about USD $500 per daily pill.

We doubted the possibility of insurance claims with such a process, even if we could get approval to have the drug covered.  Language barriers were starting to introduce challenges.  I turned, left the room, and ran, hoping to catch Nurse J before she left for the day.  I recall noting my dwindling mental acuity as I ran; instead of leaving items with Annie, my backpack flopped half zipped on one arm, a pack of pain meds still in one hand, and some papers in the other.  Clumsy and off-kilter.  Managing to catch her far away towards another building, she graciously walked back quickly with me.  After lots of back and forth, a more senior administrative person, the same person that the doc had called earlier, came in.  We all came to agreement to let the hospital accelerate the process on their part to attempt getting it directly from Pfizer Korea; failing which we’ll just fall back to ordering through government and pay for it first to start.

The gates to the outpatient cancer department corridor shut after we exited.  The second 2nd time now.  I hope this does not become habit.  7pm and we still had shots to get.  Guessing the inpatient process, since the outpatient desk was now unmanned, we somehow got to the correct area and nurse.  Having someone with us that spoke the language helped of course.

The big needle of Zoladex was administered very differently than back in the States. Just a topical rub, then the Zoladex done quickly and smoothly; without an additional pre-shot numbing Lidocaine jab.  No “are you ready?”  Then it was onto the fulvestrant.  Two needles.  One on each butt cheek. Annie asked if the needle was big too.  I paused and said no.  It was definitely narrower.  But long.  And the liquid seemed thick.  So the injection took a while, and the nurse would give her butt a good slap before each jab.   For spousal duty, I’m called in to massage the injected spot after each jab.

We arrived at the restaurant way past 7pm, of course.  Traffic had snarled A’s commute, so we all ended being there around the same time.  She brought us a popular cake from Singapore’s Bangawan Solo, Kueh Lapis, which has the fragrance of jackfruit.  Annie would come to enjoy this over the next week as a post dinner treat. It was a peaceful dinner spot, with a rare-for-Seoul quiet ambience, a good way to let the pace of the day slow down.

Fight.  Battle.  War.  Are these descriptions even apt for cancer?  Why the common framing with militaristic words?  And why do some corners of modern American psyche dislike it?  Because “losing” has a negative connotation?  I have not thought these matters through, and neither am I the afflicted one.  But my favorite sport is one where failure is the predominant experience.  There’s no shame in failure, nor in losing.  We can, however, choose the way we live.  Even when life puts us in arenas not of our own choosing.

Whatever the visual may be, Zoladex (goserelin), Fasloex (fulvestrant) and Ibrance (palbociclib) are now introduced.

September 1, 2016.  We have our first line.

Courage is strength in the face of knowledge of what is to be feared or hoped. Wisdom is prudent strength.
~ Atul Gawande, Being Mortal: Medicine and What Matters in the End