Testing a radical approach to cancer: Less chemotherapy

September 25th, 2019

Often doing less means taking a big risk. Nobody knows this better than Dr. Bernard Lown, who in 1977 began managing his cardiology patients without a coronary angiogram and subsequent surgeries. Lown was understandably nervous about going against the standard of practice; he would wake up in the middle of the night worried about a patient dropping dead.

“The family brings a lawsuit,” Lown recalled, in The Boston Globe. “We have a class-action suit, millions of dollars. It’s over — my practice, my group, my privileges at the Brigham.”

Fortunately, Lown’s results were ultimately worth the risk. The program showed that patients with stable coronary artery disease could be managed with medical treatment, diet, exercise, and stress management rather than surgery, without increasing mortality. Over the next twenty years, Lown’s group continued to manage most of their patients (many of whom had been told by other doctors that they needed surgery) with medical therapy and lifestyle changes alone, with successful results.

Now, another doctor is taking a similar risk in cancer care. Dr. Robert Gatenby, an oncologist at Moffitt Cancer Center in Tampa, FL, is testing an approach that may seem counterintuitive — using less chemotherapy to treat patients with advanced cancer. Recently research has shown that less intensive cancer treatment can be just as effective in many cases. For example, women with common early-stage breast cancer may not need chemotherapy. Similarly, using “active surveillance” for prostate cancer rather than surgery or radiation has been shown to be safe and feasible. However, this may be the first time that oncologists are using the “less is more” approach with advanced cancer patients to help them live longer. 

Gatenby got the idea from years of research and theories from evolutionary biology. Currently, the standard practice is to treat advanced cancer patients with as much chemotherapy as they can tolerate, to kill off as many malignant cancer cells as possible. However, this leaves the treatment-resistant cells behind to multiply, making the cancer harder to treat and more deadly. Gatenby theorized that treating patients with less chemotherapy would leave behind malignant cells that are susceptible to chemotherapy treatment, suppressing proliferation of the chemo-resistant cells. In this way, patients could stay alive longer with repeated chemotherapy treatments. 

Like Lown, Gatenby was nervous about the first trial of this new treatment model. “I sweated bullets worrying about what was going to happen to these men,” Gatenby said, in an interview with STAT. “To be honest, I didn’t know if it would work.” But like Lown’s experiment, Gatenby’s also showed promising results. Men with advanced prostate cancer who received less chemotherapy kept their tumors under control for 20 months more on average, compared to men receiving standard treatment. Further, men in the lower-treatment group experienced fewer side effects from chemotherapy than those receiving standard treatment. 

As Gatenby continues to test his approach, he is hopeful that the oncology community will be open to change. But he knows that it won’t happen overnight. “Medicine is fundamentally conservative. It doesn’t change easily,” Gatenby said in STAT. “Our ideas have been met by everything from indifference to anger. There is a lot of fear that patients will do worse.” 

Gatenby may be right about that; it took 25 years after Lown’s initial experiment for the cardiology community to begin to question the value of stenting for stable angina. However, as Dr. Vikas Saini writes, experiments like Gatenby’s and Lown’s are extremely valuable, because their alternative views “remind us that another world is possible.”

Rather than squash or ignore these “positive deviants” we should “encourage them, embrace them and scale them up,” said Saini.