In clinical trials for cancer, patients often overestimate the benefit


Recently, I saw a patient who drove six hours to consult with me. He was a former boxer, a light heavyweight, and had a leukemia that refused to be knocked out by a few rounds of chemotherapy. He looked like an aged version of the movie fighter Rocky, though his voice was gravelly, more like the Burgess Meredith character, Mickey Goldmill, Rocky’s trainer.

“What do I have to do to get rid of my leukemia? I’ll try anything,” he said to me earnestly. “I heard you had a study going on here. I want in!”

He was interested in enrolling in a clinical trial of a new immunotherapy treatment that harnessed a patient’s own immune system to target and eliminate leukemia cells. His doctor told him we had the trial available at our cancer center.

The clinical trial was a Phase 1 study, more dramatically called a “first in human” trial — the first time a drug is given to people following what’s called “preclinical” testing. The primary purpose of Phase 1 trials is to find the right drug dose and to assess the safety of that drug — and not to determine whether the drug actually works.

In these trials, in fact, the chance that a drug will be at all effective at treating a patient’s cancer is historically less than 15 percent.

What motivates people to enroll in trials to receive an experimental drug before its efficacy — and even its dose — has been clearly determined, and ostensibly, the purpose of such a trial has nothing to do with shrinking a person’s cancer?

What motivates patients to enroll in clinical trials?

In one study, surveys asking this very question were mailed to nearly 300 cancer trial participants. When patients were asked the primary motivation for participating in a clinical trial, 45 percent of respondents who were enrolled in Phase 1 trials said they were motivated by the possibility that they would receive medical benefits from the treatment.

The next highest motivations for adults participating in Phase 1 trials was trusting the study doctor (17 percent), to maintain hope (15 percent), and to help future patients (4 percent). This last category is considered medical altruism, as in wanting to help advance medical science. These tend to be more common in patients with better prognoses.

Why then did almost half of these patients enroll in a cancer clinical trial hoping for a drug that would work, when the goal of the trial was only to find the right drug dose?

Imagine you’re my patient, with a leukemia that has continued to burn despite multiple rounds of chemotherapy. Your doctor tells you that there aren’t any more treatment options available, so you’d better go to the university hospital nearby, or to one of the big academic hospitals where they might be running a clinical trial of a new drug.

A communication gap in signing up for a clinical trial

To someone like my patient, who feels well enough to drive six hours for a consultation, a clinical trial becomes the next treatment step, regardless of what that trial entails or any promises that the drug might work, simply because his doctor told him one exists.

Probably a more common reason, though, is that those of us involved in clinical research don’t effectively communicate the true goals of such an early phase trial.

Such ineffective communication can lead to therapeutic misconception — the belief that the purpose of the research is to directly benefit the individual patient enrolling in the trial, when in reality only future patients will benefit from the research.

Another study examined how doctors communicated the risks and benefits of participating in Phase 1 trials to 85 families of pediatric cancer patients. Risks of the drug treatments were discussed 95 percent of the time, with 81 of 85 families. It is a bit surprising that this didn’t occur 100 percent of the time, as these Phase 1 trials involved chemotherapy.

Therapeutic benefits were discussed almost as frequently — 88 percent of the time, for 75 of 85 families. Altruism was mentioned to 41 percent of families. In 13 percent of conversations, though, the clinical trial was actually described as a bridge to another therapy or to extend life — despite no evidence that these first-in-human drug treatments would even work to shrink the cancer.

‘I’m not ready to throw in the towel yet’

People with end-stage cancer pursue treatment for a variety of reasons, and are willing to withstand tremendous side effects from drugs for the potential of even tiny benefits.

As health care providers, it’s our responsibility to understand those motivations and ensure that our patients don’t enroll in a clinical trial with the wrong goal in mind — and take particular care that we don’t misinform our patients about what treatment goals are even possible.

I asked my patient if he was sure he wanted to pursue another treatment for his leukemia, given the vanishingly low chance that it would work.

“Nah doc, I’m not ready to throw in the towel yet. I’m still tough as nails!” He lifted his arms and gave the air a couple of jabs, to emphasize his point.

He qualified for the trial and spent the next month in the hospital, enduring substantial side effects to the therapy but retaining his remarkable spirit throughout. But at the end of that month, the leukemia remained despite his — and our — efforts.

I saw him in my clinic one final time before he returned home, and apologized for how he had spent what would turn out to be his final weeks. I felt terrible that he had spent this time in a foreign city, withstanding the blows of an experimental therapy, instead of being home with his family.

He waved me off. “Doc, it was worth a shot, right? And I figure, maybe you learned something by studying me, and I help someone else in the future.”

His altruism was so moving. And maybe to my patient, just having the moxie to take that treatment step — to get into the ring one more time and say he had explored every avenue — had been the point all along.

Mikkael A. Sekeres, MD, MS is chief of hematology at the Sylvester Comprehensive Cancer Center, University of Miami. He is the former chair of the FDA’s Oncologic Drugs Advisory Committee and author of the book Drugs and the FDA: Safety, Efficacy, and the Public’s Trust. Follow him on Twitter @MikkaelSekeres.

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