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Keith Stewart , MBChB , MBA , is Carlson and Nelson Endowed Director Center for Individualized Medicine and Vasek and Anna Maria Polak Professor of Cancer Research at Mayo Clinic in Scottsdale , Arizona .
Keith Stewart , MBChB , MBA
ASH Clinical News
11
Letters to the Editor
Learning Your ABC
In September ’ s Editor ’ s Corner , Keith Stewart , MBChB , MBA , argued that cytotoxic chemotherapy should be declared a thing of the past and imagined a future where hematologists embrace the rallying cry of “ anything but chemotherapy .”
In response to Dr . Stewart ’ s column , Francis A . Forte , MD , recounted his early experiences treating patients with cytotoxic chemotherapy and his hope for the future .
Dear Dr . Stewart , I was the first intern to begin an infusion of anthracycline to a patient on protocol .
Soon , anthracycline was being called “ The Red Death ” and I was considered the odd man out among my fellow interns . They probably wondered how I could be interested in hematology-oncology . Other fields were so much more promising .
I sensed then , and for a long time afterward , that there was much truth in this . I have waited for the days of oral medications , less alopecia , and good nausea control .
So , more than 56 years later – thanks to the researcher into the molecular structure and pathways of the errant cells – we are beginning to see those beacons . There is hope . “ ABC ” will not be an acronym for a blockbuster chemotherapy regimen , but a triumphant cry of joy : “ Anything but chemotherapy !”
Well , after many coffee spills and 12-hour Saturdays , I am still enthusiastic about my oddball specialty choice , I have always cherished the doctor-patient relationship , and I strive to offer hope for the hopeless and their families .
With each new attack on the inner workings of the cells and harmful side effects , my excitement grows . We are all grateful for the boundaries we have crossed in pain control and survivorship . With fewer and fewer of my patients older than me these days , I have set my sights on developing treatment schedules that work
and that my patients can tolerate .
Francis A . Forte , MD Hematology & Oncology Associates of
Englewood Englewood , New Jersey
Editor ’ s Corner
A
The content of the Editor ’ s Corner is the opinion of the author and does not represent the official position of the American Society of Hematology unless so stated .
The Decline and Fall of Cytotoxic Chemotherapy
Here , Dr . Stewart gives his take on whether cytotoxic chemotherapy should be declared a thing of the past .
S WARD ROUNDS ENDED LAST SATURDAY , a slow-brew blend of my own clinical experience and what I have seen as reproducibly disappointing outcomes welled inside me to create my strong desire to relegate cytotoxic chemotherapy to the category of failed medical experiments .
Before we get to that dramatic and inflammatory conclusion , let ’ s start with some background information : My telomeres are shortening , I need reading glasses overnight ( which I usually can ’ t find ), I yell at the television randomly , and 11 p . m . is a late night for me . Most troublesome of all , I have high-definition flashbacks to my internship on the leukemia ward , filling syringes with adriamycin , methotrexate , and mitoxantrone without wearing gloves or plastic safety glasses . This may explain the failing eyesight , the ear hair , and the strange brown spots on the back of my hands … . In what I could probably patent as an early indicator of cortical loss , what I remember most about those drugs was their scary primary-color hues of red , yellow , and blue .
Now fast-forward 30 years to last Saturday and picture me driving to work after a late night arguing with the television , carefully dodging police radar , and inevitably spilling coffee on my khakis .
Then picture me again when I discover that I am alone at the clinic – not a fellow , intern , resident , or medical student in sight . I conjure up images of how these trainees are spending their time while I ’ m at work – pretty young things pushing baby strollers while their partners squeeze fresh oranges , or unwinding in the eucalyptus steam room after their Saturday morning yoga class .
“ They wouldn ’ t get away with this in Boston or New York ,” I think to myself . “ No sir . The trainees there probably come in for rounds at 6 a . m ., they ’ re not allowed to eat until noon , and they don ’ t dare set foot outside the ward until the last discharge orders have been wrestled from a computer running on 80s-era bandwidth .”
It could be , though , that I ’ m just jealous that they get to spend that weekend in California while I ’ m stuck trying to air-dry my khakis at work .
Another day repairing the havoc wrought by malignant hematology , or our cytotoxic treatments for it , ensues . I would love to send some patients home , but defer that decision until someone who can work the computer shows up . So , I lobby any mobile patient to go outside for sunshine . However , this is America , and a lawyer has banned fresh air or trips home to collect a toothbrush ; “ patio privileges ” are dispensed with the enthusiasm of a bank loan .
Nevertheless , by noon , the coffee stains have faded , I am invigorated by patient interaction , the nurse practitioners have bailed me out again , and I am satisfied to have helped in a small way .
Then , spontaneously in the elevator , quarks collide , atoms fuse , long suppressed synapses fire , and I announce to a surprised intern ( who must have wandered in to work by accident ), “ Cytotoxic chemotherapy is a failed 50-year experiment in medical history .”
Before he can respond , I reflect that hematology is the cytotoxic success story – just look at the high-water marks of Hodgkin lymphoma , childhood acute lymphocytic leukemia , and diffuse large B-cell lymphoma – but also remind him ( with some salty language ) that so many other patients flail through months of awfulness .
I wrap up my soliloquy by theorizing that , like blood-letting , radical mastectomy , tonsillectomy , and wisdom teeth extraction , cytotoxic chemotherapy also will soon be equally hard to justify to those who come after us .
En route home , I imagine colleagues around the world re-enacting my weekend rounds with much the same cast , and speculate that , with a collective willingness , we could soon push aside the veil of modest success to embrace the rallying cry of “ ABC ” or “ anything but chemotherapy .” The required tools are being molded , iterated , and sharpened : more potent and specific kinase inhibitors , immune modulators , engineered cellular products , and viral oncolytics , all guided by genomics . There are also protein degraders , metabolism modifiers , and things we haven ’ t even yet imagined .
It is time to declare the beginning of the end – not to cancer , but to failed cancer treatments – and to band together around a better way : to reward – not discourage – physician engagement in clinical investigation and to make trial participation a badge of honor for patients ; to make it socially dishonorable to choose the easier path of palliative cytotoxic therapies when a novel approach is there to be tested ; to send grant dollars to places where new approaches are embraced and urgency is palpable ; to actively discourage timid and incremental change ; to not be limited by the economic doomsayers ; to focus on answers first and to remember that patent protections are short in the long arc of human history ; to do all of this with a ceaseless velocity .
Maybe then , on Saturdays , my drive to the hospital will be energized , my step more purposeful , and my memories of administering noxious and often ineffective poisons consigned to my longterm hippocampal memory where they belong . Maybe the trainees will show up – even when they don ’ t have to – just because they are inspired . And maybe I ’ ll be able to find my reading glasses .
AML is swarming with challenges
Have a comment about this editorial ? Let us know what you think ; we welcome your feedback . Email the editor at ACNEditor @ hematology . org .
September 2016 Editor ’ s Corner
14 ASH Clinical News
Impact of disease
• Acute myeloid leukemia ( AML ) is the most common type of leukemia in adults , accounting for approximately 25 % of leukemia diagnoses , with an estimated 19,950 new cases in the United States this year 1 , 2
• The 5-year survival rate in patients with AML is about 26 % 1
• An estimated 10,430 patients will die from AML this year 1
AML evolves rapidly because of its polyclonal and heterogeneous features , contributing to the clinical challenges of this disease 3
• As indicators of prognosis , cytogenetic and molecular mutation testing are recommended by the National Comprehensive Cancer Network ® ( NCCN ® ) at diagnosis 4
• Evaluation of molecular mutations may be important for risk assessment and prognosis to help guide treatment decisions 4