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Despite decades of progress in cancer treatment, dosing remains stuck in the past and patients are likely suffering unnecessary treatment-related side effects, according to authors of a recent survey-based analysis.

Dosage recommendations on drug labels are still typically based on the maximum tolerated dose from phase 1 testing, a holdover from when chemotherapy was about the only thing medical oncologists had to offer patients.

Experts now question the more-is-better approach for chemotherapy as well as for targeted and immunotherapies where lower, less toxic doses often work as well as higher ones.

But with maximum tolerated dose still holding sway, many patients receive this dose when starting therapy and can experience significant treatment-related side effects.

The survey-based analysis, published in the Journal of Clinical Oncology, supported this view.

The survey, which asked patients with metastatic breast cancer about the toxicities associated with the maximum tolerated dose, found that nearly 90% of respondents reported at least one significant treatment-related side effect.

Overall, 1221 patients completed the 27-question survey, developed by the Patient-Centered Dosing Initiative (PCDI), a patient advocacy group launched in 2019 to improve treatment of metastatic breast cancer.

The survey aimed to assess the prevalence and severity of patients' treatment-related side effects, communication between patients and physicians about these issues, as well as perceptions about the efficacy of higher vs lower doses and a willingness to discuss different dosing strategies.

Patients were invited to take the survey on social media. Most patients were postmenopausal, and almost half had been diagnosed in the past 2 years. Treatments included targeted, endocrine, and chemotherapy, as well as radiation, surgery, and immunotherapy.

Overall, about 86% of patients (1051 of 1221) reported at least one significant treatment-related side effect. Among these patients, more than 20% went to the emergency room or hospital as a result, and 43.2% missed at least one cancer treatment.

The most common side effects were fatigue, nausea, low blood counts, diarrhea, and neuropathy.

Almost all respondents (97.6%) told their doctors about the treatment toxicities. More than half (54.2%) received a dose reduction to minimize the side effects, and among these patients, 82.6% reported symptom relief.

The analysis had several limitations, however, including possible selection bias because only patients with internet access could participate, an underrepresentation of minority populations, and self-reported side effects that could not be confirmed.

Still, the results indicate that patients are likely struggling with potentially unnecessary treatment-related side effects because of an outdated dosing paradigm, said investigators led by PCDI founder Anne Loeser, BS, who recently died of metastatic breast cancer.

The group continues to work with the US Food and Drug Administration on initiatives to optimize cancer drug dosing and update labels. But in the meantime, PCDI recommends talking with patients about dosing options. The survey indicated that such conversations are welcome.

Nearly all survey respondents (92.3%) said they would be willing to discuss alternative dosing options to optimize quality of life. One in five, however, did not know that dose reductions were an option to control side effects. And more than half of respondents (53.3%) did not think the highest dose was necessarily the most effective.

There are "no real surprises" in the survey, but "clearly patients want to be engaged in decision-making," said William J. Gradishar, MD, a breast oncologist at Northwestern University, Chicago, who discussed the initial survey results when Loeser presented them in 2021 at the American Society of Clinical Oncology annual meeting. The survey "really highlights the need for a two-way conversation" between patients and caregivers throughout treatment.

"We have to recognize that many of our treatments do not actually improve survival, and if they do, in some cases, it's quite modest, so anything we can do to make therapy more tolerable is important," especially when the goal of care is palliation, not cure, said Gradishar.

No funding was reported for the work. Loeser and Gradishar did not have any disclosures.

M. Alexander Otto is a physician assistant with a master's degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com