Book review: The Death of Cancer: After Fifty Years on the Front Lines of Medicine, a Pioneering Oncologist Reveals Why the War on Cancer Is Winnable–and How We Can Get There, by Vincent T. DeVita, and Elizabeth DeVita-Raeburn.
In my last review of a medical book, I was disappointed about the lack of explanation as to why medical advances get deployed much too slowly, particularly cancer treatments.
By some strange coincidence, the next medical book I read, published a decade earlier, provides some valuable insights into those problems.
This is a memoir of both luck and skill. DeVita is uniquely qualified to describe the origins of the war on cancer, due to a career that included diagnosing patients, running clinical trials, and serving as director of the National Cancer Institute.
Pioneering Chemotherapy
The first two chapters portray DeVita as sometimes regretting that he doesn’t find a way around rules that keep him from using his judgment to cure a patient, and sometimes successfully helping patients by overriding standard procedure.
He wants more experimentation, at least in cases where the prognosis is death, and seems concerned that rules are being too strictly enforced.
But he sounds different by chapter 4. By then, he has published a study describing a treatment that cures many Hodgkin lymphoma patients, at a time when most doctors were convinced that cancer was incurable.
He is then disturbed that many doctors use their judgment to modify his protocol, and complain that his protocol doesn’t work. It sounds an awful lot like he’s just reversed his position, and is now complaining that the doctors are using too much judgment.
Is he contradicting himself, or did I make inappropriate inferences? I suspect it’s mostly me generalizing too much. He mostly wants more experimentation, but he’s focused mainly on whether individual decisions were good or bad, and not generalizing much to any lesson about whether the rules should be followed more strictly or less.
This book is one man’s perspective on history, not an attempt at solving the remaining problems. For much of the book, I kept grasping for big lessons, and only finding small ones.
Deployment
His story of the Hodgkin lymphoma cure (MOPP)provides some insight into why doctors got wildly inconsistent results when they claimed to have deployed it.
A bit of what went wrong is that doctors sometimes used a drug that was a favorite of the local hospital in place of one of the four drugs used in MOPP. Something is puzzling about this, but I think that mostly reflects attitudes of the 1960s that have little relevance to modern medicine.
The more serious problem was that doctors would reduce dosages compared to those used in the original trial. MOPP seems to depend on hitting the cancer hard enough to completely eradicate it. Partial damage to cancer seems to leave the remaining cancer at least as dangerous as it originally was.
Why would doctors reduce the dosage? Maybe partly because they didn’t believe that cancer could be cured. But mainly because it was obvious that MOPP had terrible side effects. As in, patients couldn’t take public transit home from the treatment, due to the vomiting. They might need a year to recover from the nerve damage. With the medical profession being somewhat reluctant to agree that drugs could save lives of terminal cancer patients, much less agree on how the drugs worked, doctors were reluctant to knowingly cause those side effects.
He writes (about an early, less proven version of MOPP):
I knew why other doctors were reluctant to follow our lead. Cancer was among the most challenging of diseases. We knew almost nothing about why it happened or how it happened, and a sense of powerlessness surrounded it … And medicine is, by definition, a conservative field.
I want that conservatism when I have a problem that doctors can reliably cure. I want them to follow moderately strict rules in such cases. But I want a very different attitude when the standard of care will yield poor results.
I’m guessing that either doctors find it hard to switch attitudes like that, or that medicine selects for people who are reluctant to switch away from conservatism.
DeVita seems fairly unusual in his ability to be comfortable about causing terrible side-effects while maintaining a focus on his patients’ well-being.
Protectionism
A fair amount of the resistance to new cancer treatments comes from the standard problem of change being a threat to existing careers.
Radiology, surgery, and chemotherapy are very different specialties. Doctors specialize enough that their expertise can lose much of its value when advances in one of those three approaches obsoletes another one.
DeVita indicates that this was an important obstacle to adopting chemotherapy.
Theory versus Pragmatism
There’s not much theory in this book. DeVita seems to mostly focus on experiments that are guided by vague intuitions. At one point he admits that he’s just grasping at straws.
Some of the conflicts that he encounters seem related to the tension between pure science and applied science. Some people want to prioritize finding a complete understanding of how cancer and cancer treatments work. DeVita is too impatient for that, and wants to treat patients faster than the pure science approach allows.
DeVita has the beginnings of a theory, namely that cancer cells which survive an initial treatment become smarter, and harder to kill. That theory is good enough to produce better-than-random guesses about cancer treatments. But “smarter” seems like not quite the right word. The theory might be a bit too vague to justify frequent academic publications on which theorists thrive.
What lessons should we draw from this? It seems important to avoid becoming overconfident in a bad theory. But I don’t see much in the way of a general lesson about theory versus pragmatism.
The FDA
DeVita rants against the FDA’s unreasonable bias toward saying no to drugs.
The rate-limiting step in eradicating cancer today is not the science but the regulatory environment we work in.
His first encounter with the FDA seems to have been when he sponsored ads advocating a high fiber diet, in a way that could be interpreted as saying that a particular brand of cereal could prevent cancer. DeVita’s boss refused to cave in to the FDA’s threatened sanctions, and the FDA backed down.
DeVita had less success at fighting the FDA’s obstacles to deploying new cancer drugs. He says that Congress never authorized the FDA to require additional trials to prove drug efficacy. He implies that safety trials typically provide enough evidence to establish efficacy.
He says the FDA sometimes unethically requires trials to compare new drugs to the standard of care in cases where the standard of care is known to result in fairly quick death.
DeVita complains about the requirement that cancer drugs be evaluated by their 5-year survival rates. Instead, he wants their efficacy evaluated at least in part by whether they cause complete remission.
It seems clear that complete remission, to the extent that it can be observed, would enable good drugs to reach the market much faster than the 5-year survival end point. I’m guessing that the FDA is reluctant to use complete remission because there’s enough subjectivity in measuring it that drug companies would find ways of overstating how much remission their drugs produce. Maybe DeVita underestimates this problem because the drug trials that he has conducted were done within the government.
What I infer is that what we need is for more drug trials to be done by government agencies, such as the National Cancer Institute, whose biases are weaker than those of drug companies. In that case, it would become more appropriate to rely more on subjective judgments about how well a treatment works.
DeVita is at least half right in his criticisms of the FDA, but this book is just an overview of his beliefs. He doesn’t provide rigorous enough arguments to convince fans of the FDA.
Concluding Thoughts
The book was well worth reading, even though it provided much less hope than the title led me to expect.
I suspect he overstates the benefits of chemotherapy, by focusing almost exclusively on cases where it works.
I didn’t see anything here that qualifies as a plan for winning the war on cancer. For that, see Openwater, or Aubrey de Grey’s WILT?.
As Scott Alexander summarized the war on cancer:
If they’re really old, maybe they remember victories of that scale over polio and smallpox. If those were their hopes, it’s right for them to feel disappointed. But I come from a generation that doesn’t expect much, and I think the evidence suggests my low expectations have more or less been met.
I’m going to be stubborn, and insist that we should aim for a polio-scale victory. DeVita cooperated with people who misled the public into thinking that the Nixon-era war on cancer would produce victory in five years, but he never believed in a vision with that much optimism.
DeVita claims that the economic benefits of cancer research have been more than 1000 times the cost, based on the paper THE VALUE OF HEALTH AND LONGEVITY (which I think only partly justifies DeVita’s claim). I’m willing to believe that DeVita is mostly right here, and that one of the best uses of money would be to increase funding for the kinds of cancer research that DeVita has been involved in.
Yet my intuition tells me that it would be even better to shift more research money to paradigm-shifting cancer research that aims for a clear-cut victory.