1. Harpham, Wendy S. MD, FACP

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When you have no standard therapies left to try and your patients are ineligible for clinical trials, do you ever mention promising-but-unproven therapies? Gina Kolata addressed this controversial topic in the article "'Desperation Oncology'" (New York Times, April 26, 2018). Against a backdrop of President Trump signing the Right to Try Act and the media trumpeting triumphs of novel immunotherapies, Kolata quoted a few clinicians who do-and others who don't-prescribe novel immunotherapies outside trials.

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Wendy S. Harpham, MD... - Click to enlarge in new windowWendy S. Harpham, MD, FACP.

I was equally interested in how clinicians presented the option to patients as in how they justified their decision. For me, this dilemma was personal. Months ago, my sister tearfully called me after her oncologist recommended a checkpoint inhibitor as her last hope. She knew I'd made difficult treatment decisions myself. Decades earlier, I'd put my hope in a phase I trial to treat a recurrence for which standard therapies were palliative. Unfortunately for my sister, she was ineligible for any trials, and palliative therapies had already failed, which dialed up her desperation.


To help her make the best treatment decision, I took a deep breath and asked myself, "What are ethical, compassionate ways to answer patients who inquire about-or demand-unproven therapies?" A return to fundamental principles of decision-making offered some guidance.


In every clinical scenario, whether we're motivated by professional compassion or familial love, the goal remains the same: to guide patients to informed treatment decisions in keeping with their values. The challenges are especially great when treatments are so new you don't yet have outcomes data to help weigh the risks and benefits, and when patients want you to do something, anything, to help them survive.


Do desperate times call for desperate measures? Is it appropriate for clinicians to "engage in a different kind of oncology than the rational guideline thought...offering unproven drugs to some terminal patients as a roll of the dice?" Is it ever okay, as Kolata reported, for oncologists to ask patients a diplomatic version of "Do you want to try an immunotherapy drug before you die?"


Kolata's provocative paraphrasing triggered some insights that might prove useful. For starters, any variation of "trying an intervention before you die" presents patients a choice between holding on to hope of recovery or letting go of that hope. Put another way, patients are being asked to choose between the uncertainty of an intervention or the certainty of death. Both choices create bias to try.


Both are false dichotomies, too. Patients with advanced disease do not have to let go of hope of recovery when they stop cancer treatments (Oncology Times 2011;33(13):37). Patients can accept they'll very likely die within 6 months while hoping to live long enough to benefit from new treatments. They can hope to be the rare patient who inexplicably recovers, if that hope helps them emotionally.


Other hopes are linked to each option, too, and talking about them helps minimize bias. Unproven therapies tap into patients' hope of being a pioneer or a cancer warrior, fighting to the last breath. Hospice offers hope of maximizing quality of life in whatever time they have and hope of living longer than had they continued with treatment.


Then there's the issue of the uncertainty associated with unproven therapies. Patients are intimately familiar with the uncertainty of standard therapies. Since their diagnosis, they have proceeded with treatments they knew only "might" work well for them.


Anyone can tell your patient, "the promising new immunotherapy might work for you." I have no problem with that. It might. The problem is you are not "anyone." Patients presume your recommendations are based on evidence of efficacy, and not on an anecdote, a gut feeling, or your hope of getting a lucky roll of the dice.


Patients can make wise decisions only if they understand that your past recommendations of standard therapies weighed in the certainty that those therapies had demonstrated benefit in groups of patients like them. In contrast, with unproven therapies you don't yet know if the treatment helps patients like them, makes no difference, or makes things worse.


Of note, five of the oncologists interviewed by Kolata added comments like, "If I was a patient, I want my doc to do everything"-meaning "do everything that might increase the chance of surviving." The million-dollar question is: Are you increasing patients' chance of survival with an unproven therapy?


There is an answer. Trials will soon uncover that answer. Until then, we don't know whether you are helping-a notion that jars all our sensibilities because we feel hopeful about promising therapies.


Feeling hopeful can lead clinicians astray. To that point, Kolata highlights "the pitfalls of treating patients before all the evidence is in." She references the cautionary tale of compassionate, hopeful oncologists who in the 1980s and 1990s gave high-dose chemo to women with breast cancer outside clinical trials. That is, until trials demonstrated worse outcomes.


Desperate situations call for equanimity. Help patients process difficult information and make the best decision by first...


* acknowledging the difficulty of the situation


* emphasizing the value of weighing all the pros and cons


* affirming your desire to provide whichever interventions might help


* expressing confidence in their ability to make the best decision for them



During the discussion, clarify how unproven therapies differ from standard ones: Nobody today knows if a new treatment might help or harm, no matter how promising the theories behind it or exciting the anecdotes of recoveries.


Review the pros and cons-and the hopes-associated with pursuing an unproven therapy and with enrolling in hospice. Explain the best and worst possible outcomes for each option. By painting a picture of patients' chances and their quality of life with each option, you equip them to choose a treatment path in keeping with their values-and minimize regret if things don't go well.


In desperate situations, patients look to you for hope. By helping patients accept the limits of what we know and appreciate all we do know, you nourish patients' hope of making the best decision for them.