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Undark — The Side Effect Roulette of Cancer Treatment

Undark — The Side Effect Roulette of Cancer Treatment

The stomach pain stopped Vickie-Lee Wall in her tracks. “The first time the pain got that bad, I honestly thought something had burst in my gut,” said the 64-year-old New Jersey woman, who has stage 4 lobular breast cancer.

Her oncologist had prescribed two drugs, including a targeted medication called abemaciclib, after the cancer spread to Wall’s spine in 2018. Initially the pain was relatively mild. But then it ratcheted up until, three months later, Wall begged her physician for relief. “The next visit with him I went, ‘I can’t do this at this dose.’”

Wall, who usually checks the label before starting a new medication, notes that abdominal pain is listed as a possible side effect of the drug. But while a few others, such as diarrhea, were described as potentially severe, there was no such wording regarding abdominal pain, she said.

People with cancer typically assume that side effects from chemotherapy and other drug treatments are part of the tradeoff to treat a life-threatening disease. But some researchers and patient advocates maintain that the information provided about potential side effects, particularly more subjective ones like pain and fatigue, doesn’t necessarily provide the real-world insights that cancer patients crave.

Clinical trials typically are well designed to measure the effectiveness and safety of cancer drugs, but they often don’t similarly capture “the tolerability side” that patients really care about, said Hillary Andrews, director of regulatory and research partnerships for the Friends of Cancer Research, a nonprofit advocacy organization based in Washington, D.C. “They want to understand how others have experienced this drug, and how it could potentially impact them,” she said.

For instance, a patient’s diarrhea may not be frequent enough to constitute a safety concern but still be urgent enough that someone is reluctant to leave home, Andrews said. Federal officials have begun to encourage drug study leaders over the last decade to collect more such information related to tolerability, called patient-reported outcomes. But it’s not required, and neither is the reporting of those patient measures, including on the drug label, she said.

“The first time the pain got that bad, I honestly thought something had burst in my gut.”

Proponents acknowledge that adding more questions to cancer drug studies should be pursued carefully, ensuring that the findings are relevant to patients and that data collection doesn’t become overly burdensome. The bottom line, though, is that getting a better handle on a drug’s tolerability matters because it influences whether the patient will stick with the treatment, said Devin Peipert, a researcher at Northwestern University’s Feinberg School of Medicine in Chicago who studies patient-reported measures.

Patients drop out of drug studies for various reasons, including the progression of their cancer. But “sometimes it’s because the patient or the doctor has felt that the patient just has reached a level of side effects that is not tolerable,” he said. “And within that, it’s the patient just saying, ‘I’m not going to do this anymore.’”

In drug studies, researchers track hundreds of potential side effects and other adverse events — from nausea and anemia to hospitalizations and deaths — using a set of criteria such as those established by the National Cancer Institute. Some side effects and drug toxicities are identified through blood work and other lab testing. Others involve self-reported symptoms, such as fatigue or diarrhea.

Clinicians collect that information from patients and, in the U.S., typically grade the side effects’ severity on a five-point scale based on the federal agency’s criteria, with 5 referring to an adverse effect that results in death. Side effects that aren’t considered life-threatening are typically graded from 1 to 3; grade 3 abdominal pain, for example, describes pain that’s severe enough to limit basic self-care, such as bathing or dressing oneself. Wall, when she learned about that grading criteria, wrote in an email to Undark: “I’d say doubling over is definitely a 3 on their scale.”

But the collected details usually “are not patient-reported outcomes that are directly from the patient — these are interpretations of clinicians,” said Michelle Tregear, chief programs officer at the National Breast Cancer Coalition, a D.C.-based research and lobbying organization. Clinicians often underreport the frequency and severity of symptoms compared with what patients share, research has found. One 2015 study, which looked at three randomized trials involving 1,090 patients, found that physicians consistently underreported six side effects, including constipation, hair loss, and nausea. For example, half of patients across the three studies reported constipation, but physicians only reported it for 18.6 percent of patients.